trešdiena, 2017. gada 26. aprīlis

Reversing Aging


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                                Reversing Aging

   The achievements of modern civilization make it possible to predict that the representatives of the average generation currently residing in economically developed countries will have the conditions for a significant increase in the average life expectancy (within about a hundred years). At the same time, opportunities will be created to rejuvenate the aging body. Along with establishing the biological and cybernetic symbiosis, a foundation is laid for the immortality of the human personality.
    Here are a few publications that help look into this predictable future.
    It should be noted that such results of human progress can also become a real threat to the public order organized on the principles of humanism. This may materialize:
1)    if immortality is obtained by the heads of states – dictators who will not hesitate to proclaim their authority as eternal and autocracy as the best form of ruling people;
2)    if artificial intelligence becomes the dominant force even before its ethical humanization.
    To prevent such risks of the development of the civilization, it is vital to gradually, step by step, reform democracy into a true rule of the people, eliminating its current manipulative nature and promoting the growth of a wise electorate (see the article Cleansing of Realpolitik: the Options) : http://ceihners.blogspot.com/

Ageless: The New Science of Getting Older Without Getting Old

Andrew Steele

 With the help of science, could humans find a way to become old without getting elderly, a phenomenon otherwise known as "biological immortality"? In Ageless, Andrew Steele, research fellow at Britain's new and largest biomedical laboratory, the Francis Crick Institute, shows us that the answer lies at the cellular level. He takes us on a journey through the laboratories where scientists are studying every aspect of the cell--DNA, mitochondria, stem cells, our immune systems, even age genes that can lead to a tenfold increase in life span (in worms, anyway)--all in an effort to forestall or reverse the body's (currently!) inevitable decline. With clear writing and intellectual passion, Steele shines a spotlight on a revolution already under way and offers reality-based hope. https://www.goodreads.com/en/book/show/52954648


08-24-21

These 4 tech breakthroughs could help people live to 200 years old

Genetic engineering, regenerative medicine, wearables, and AI combine to form a powerful antidote to aging

BY SERGEY YOUNG

We live in a unique time when for the first time in human history there is a real opportunity to extend our lives dramatically. Recent scientific discoveries and technological breakthroughs that soon will translate into affordable and accessible life-extending “tools” will let us break the sound barrier of the current known record of 122 years. I am talking about breakthroughs in genetic engineering, regenerative medicine, healthcare hardware, and health data.

Very soon, slowing, reversing, or even ending aging will become a universally accepted ambition within the healthcare community. Technology is converging to make this a certainty. Developments in the understanding and manipulation of our genes and cells, in the development of small-scale health diagnostics, and in the leveraging of data for everything from drug discovery to precision treatment of disease are radically changing how we think about healthcare and aging.

When I speak of the Longevity Revolution, what I really mean is the cumulative effect of multiple breakthroughs currently underway across several fields of science and technology. Together, these parallel developments are forming the beginning of a hockey-stick growth curve that will deliver world-changing outcomes.

THE GENETIC ENGINEERING BREAKTHROUGH

Completed in 2003, the Human Genome Project successfully sequenced the entire human genome—all 3 billion nucleotide base pairs representing some 25,000 individual genes. The project, arguably one of the most ambitious scientific undertakings in history, cost billions of dollars and took 13 years to complete. Today, your own genome can be sequenced in as little time as a single afternoon, at a laboratory cost of as little as $200.

The consequences of this feat are nothing short of revolutionary. Gene sequencing allows us to predict many hereditary diseases and the probability of getting cancer. This early benefit of gene sequencing became widely known when Angelina Jolie famously had a preventative double mastectomy after her personal genome sequencing indicated a high vulnerability to breast cancer. Genome sequencing helps scientists and doctors understand and develop treatments for scores of common and rare diseases. Along with advances in artificial intelligence, it helps determine medical treatments precisely tailored to the individual patient.

Longevity scientists have even identified a number of so-called longevity genes that can promise long and healthy lives to those who possess them. Scientists now understand far better than ever before the relationship between genes and aging. And while our genes do not significantly change from birth to death, our epigenome—the system of chemical modifications around our genes that determine how our genes are expressed—does. The date on your birth certificate, it turns out, is but a single way to determine age. The biological age of your epigenome, many longevity scientists now believe, is far more important.

Best of all, however, science is beginning to offer ways to alter both your genome and epigenome for a healthier, longer life. New technologies like CRISPR-Cas9 and other gene-editing tools are empowering doctors with the extraordinary ability to actually insert, delete, or alter an individual’s genes. In the not terribly distant future, we will be able to remove or suppress genes responsible for diseases and insert or amplify genes responsible for long life and health.

Gene editing is just one of the emerging technologies of the genetic revolution: Gene therapy works by effectively providing cells with genes that produce necessary proteins in patients whose own genes cannot produce them. This process is already being applied to a few rare diseases, but it will soon become a common and incredibly effective medical approach. The FDA expects to approve 10 to 20 such therapies by the year 2025.

THE REGENERATIVE MEDICINE BREAKTHROUGH

Another major transformation driving the Longevity Revolution is the field of regenerative medicine. During aging, the body’s systems and tissues break down, as does the body’s ability to repair and replenish itself. For that reason, even those who live very long and healthy lives ultimately succumb to heart failure, immune system decline, muscle atrophy, and other degenerative conditions. In order to achieve our ambition of living to 200, we need a way to restore the body in the same way we repair a car or refurbish a home.

Several promising technologies are now pointing the way to doing just that. While it is still quite early, there are already a few FDA-approved stem cell therapies in the United States targeting very specific conditions. Stem cells—cells whose job it is to generate all the cells, tissues, and organs of your body—gradually lose their ability to create new cells as we age. But new therapies, using patients’ own stem cells, are working to extend the body’s ability to regenerate itself. These therapies hold promise for preserving our vision, cardiac function, joint flexibility, and kidney and liver health; they can also be used to repair spinal injuries and help treat a range of conditions from diabetes to Alzheimer’s disease. The FDA has approved 10 stem cell treatments, with more likely on the way.

It’s one thing to replenish or restore existing tissues and organs using stem cells, but how about growing entirely new organs? As futuristic as that sounds, it is already beginning to happen. Millions of people around the world who are waiting for a new heart, kidney, lung, pancreas, or liver will soon have their own replacement organs made to order through 3D bio-printing, internal bioreactors, or new methods of xenotransplantation, such as using collagen scaffoldings from pig lungs and hearts that are populated with the recipient’s own human cells.

Even if this generation of new biological organs fails, mechanical solutions will not. Modern bioengineering has successfully restored lost vision and hearing in humans using computer sensors and electrode arrays that send visual and auditory information directly to the brain. A prosthetic arm developed at Johns Hopkins is one of a number of mechanical limbs that not only closely replicate the strength and dexterity of a real arm but also can be controlled directly by the wearer’s mind—just by thinking about the desired movement. Today, mechanical exoskeletons allow paraplegics to run marathons, while artificial kidneys and mechanical hearts let those with organ failure live on for years beyond what was ever previously thought possible!

THE HEALTHCARE HARDWARE BREAKTHROUGH

The third development underpinning the Longevity Revolution will look more familiar to most: connected devices. You are perhaps already familiar with common wearable health-monitoring devices like the Fitbit, Apple Watch, and Ōura Ring. These devices empower users to quickly obtain data on one’s own health. At the moment, most of these insights are relatively trivial. But the world of small-scale health diagnostics is advancing rapidly. Very soon, wearable, portable, and embeddable devices will radically reduce premature death from diseases like cancer and cardiovascular disease, and in doing so, add years, if not decades, to global life expectancy.

The key to this part of the revolution is early diagnosis. Of the nearly 60 million lives lost around the globe each year, more than 30 million are attributed to conditions that are reversible if caught early. Most of those are noncommunicable diseases like coronary heart disease, stroke, and chronic obstructive pulmonary disease (bronchitis and emphysema). At the moment, once you have gone for your yearly physical exams, stopped smoking, started eating healthy, and refrained from having unprotected sex, avoiding life-threatening disease is a matter that is largely out of your hands. We live in a world of “reactive medicine.” Most people do not have advanced batteries of diagnostic tests unless they’re experiencing problems. And for a large percentage of the world’s population, who live in poor, rural, and remote areas with little to no access to diagnostic resources, early diagnosis of medical conditions simply isn’t an option.

But not for long. Soon, healthcare will move from being reactive to being proactive. The key to this shift will be low-cost, ubiquitous, connected devices that constantly monitor your health. While some of these devices will remain external or wearable, others will be embedded under your skin, swallowed with your breakfast, or remain swimming through your bloodstream at all times. They will constantly monitor your heart rate, your respiration, your temperature, your skin secretions, the contents of your urine and feces, free-floating DNA in your blood that may indicate cancer or other disease, and even the organic contents of your breath. These devices will be connected to each other, to apps that you and your healthcare provider can monitor, and to massive global databases of health knowledge. Before any type of disease has a chance to take a foothold within your body, this armory of diagnostic devices will identify exactly what is going on and provide a precise, custom-made remedy that is ideal just for you.

As a result, the chance of your disease being diagnosed early will become radically unshackled from the limitations of cost, convenience, and medical knowledge. The condition of your body will be maintained as immaculately as a five-star hotel, and almost nobody will die prematurely of preventable disease.

THE HEALTH DATA INTELLIGENCE BREAKTHROUGH

There is one final seismic shift underpinning the Longevity Revolution, and it’s a real game-changer. Pouring forth from all of these digital diagnostic devices, together with conventional medical records and digitized research results, is a torrent of data so large it is hard for the human mind to even fathom it. This data will soon become grist for the mill of powerful artificial intelligence that will radically reshape every aspect of healthcare as we know it.

Take drug discovery, for instance. In the present day, it takes about 12 years and $2 billion to develop a new pharmaceutical. Researchers must painstakingly test various organic and chemical substances, in myriad combinations, to try to determine the material candidates that have the best chance of executing the desired medical effect. The drugs must be considered for the widest range of possible disease presentations, genetic makeup, and diets of targeted patients, side effects, and drug interactions. There are so many variables that it is little short of miraculous that our scientists have done so much in the field of pharmaceutical development on their own. But developing drugs and obtaining regulatory approval is a long and cash-intensive process. The result is expensive drugs that largely ignore rarer conditions.

AI and data change that reality. Computer models now look at massive databases of patient genes, symptoms, disease species, and millions of eligible compounds to quickly determine which material candidates have the greatest chance of success, for which conditions, and according to what dose and administration. In addition to major investments by Big Pharma, there are currently hundreds of startups working to implement the use of AI to radically reshape drug discovery, just as we saw happen in the race to develop COVID-19 vaccines. The impact that this use of AI and data will have on treating or even eliminating life-threatening diseases cannot be overstated.

But that is not the only way that artificial intelligence is set to disrupt healthcare and help set the Longevity Revolution in motion. It will also form the foundation of precision medicine—the practice of custom-tailoring health treatments to the specific, personal characteristics of the individual.

Today, healthcare largely follows a one-size-fits-all practice. But each of us has a very unique set of personal characteristics, including our genes, microbiome, blood type, age, gender, size, and so on. AI will soon be able to access and analyze enormous aggregations of patient data pulled together from medical records, personal diagnostic devices, research studies, and other sources to deliver highly accurate predictions, diagnoses, and treatments, custom-tailored to the individual. As a result, healthcare will increasingly penetrate remote areas, becoming accessible to billions of people who today lack adequate access to medical care.

I predict that the development of AI in healthcare will change how we live longer, healthier lives as radically as the introduction of personal computers and the internet changed how we work, shop, and interact. Artificial intelligence will eliminate misdiagnosis; detect cancer, blood disease, diabetes, and other killers as early as possible; radically accelerate researchers’ understanding of aging and disease; and reestablish doctors as holistic care providers who actually have time for their patients. In as little as 10 years’ time, we will look back at the treatment of aging and disease today as quite naive.

The Longevity Revolution lives not in the realm of science fiction but in the reality of academic research laboratories and commercial technology R&D centers. The idea of aging as a fixed and immutable quality of life that we have no influence upon is ready to be tossed into the dustbin of history.

https://www.fastcompany.com/90666754/end-of-aging 

Can We Stop Aging?

What really happens to our bodies when we age — and could we find a way to slow it down?

https://www.youtube.com/watch?v=DvFAS1JpzPo  

How Old Can Humans Get?

 By Bill Gifford  He  is co-author of the New York Times bestseller Outlive: The Science & Art of Longevity

 July 31, 2023

 An expert on aging thinks humans could live to be 1,000 years old—with a few tweaks to our genetic “software” …:

https://www.scientificamerican.com/article/how-old-can-humans-get

 How To Reverse Aging in Humans

01.19.2023

  • Biotech approaches, clearing senescent cells, and lifestyle approaches can all help to reverse aging.
  • No matter your age, you can slow and even reverse aging by eating healthy, taking supplements, exercising, fasting, and implementing other tips from this page.

Slowing down aging is great, but what about actually reversing aging?

Reversing aging would mean making an old organism young again. Is it possible?

What may come as a surprise to many, the answer is yes! In the last few years, scientists have shown that it’s actually possible to partially reverse aging: they succeeded in making old organisms younger. 

There are many ways to do this, via cutting-edge biotechnologies, and – to a lesser extent – via specific lifestyle interventions. 

Let’s start with a few biotech approaches to reverse aging, before we cover lifestyle interventions. 

Epigenetic rejuvenation  

The epigenome is the molecular machinery that determines which genes are switched on or off. Unfortunately, the older we get, the more the epigenome gets dysregulated.

For example, cancer promoting genes are switched on (increasing our risk of cancer), and housekeeping and protective genes are switched off. This epigenetic dysregulation is one of the causes of aging. 

However, it’s possible to reprogram this dysregulated, old epigenome back to a younger state. 

This can, for example, be done by upregulating in a cyclical way (not continuously) four specific Yamanaka factors (R). These Yamanaka factors are proteins that can change the epigenome in cells. Yamanaka factors have been previously used to convert differentiated cells, like skin cells, neurons or muscle cells into stem cells (R), a ground-breaking discovery for which the Nobel Prize was awarded (R). 

The Yamanaka factors can reprogram differentiated cells (non-stem cells) by changing the epigenome.

Scientists discovered that when Yamanaka factors are upregulated only for a short while in animals, their cells also became younger (a bit more “stem cell-like”), in the sense that their organs were better able to regenerate, and many other aging symptoms were undone or drastically reduced (R).

Other studies discovered that instead of using four Yamanaka factors, also three Yamanaka factors can be used to reprogram cells (R), and that even other transcription factors can be used, like Msx1 (R).

This kind of epigenetic reprogramming approach to aging is called “epigenetic rejuvenation”.

Epigenetic rejuvenation has gathered a lot of interest, both from the scientific community and from investors.

Scientists like Juan Carlos Izpisúa BelmonteManuel SerranoDavid Sinclair, and Alejandro Ocampo are some of the leaders in the field of epigenetic reprogramming.

Large companies like Alphabet (Google), which founded the longevity company Calico, and well-known investors like Jeff Bezos (the founder of Amazon) are pouring money into epigenetic rejuvenation hoping that one day this process will turn back the clock in humans.

However, there are some hurdles to overcome. Too much epigenetic reprogramming can lead to teratomas for example, which are tumors consisting of tissue growth that has gone haywire. Using less Yamanaka factors (e.g. two or three) or using them only for a short amount of time can substantially reduce this risk.

 Clearing senescent cells 

Another way to make old animals younger again is by clearing away senescent cells.

The older we get, the more senescent cells accumulate in our body. These “zombie” cells refuse to die and secrete many harmful substances that damage the healthy neighboring cells.

Senescent cells in the skin contribute to a sagging skin, senescent cells in blood vessel walls contribute to stiffer blood vessels, senescent cells in the liver, fat and pancreas impair metabolic function, and so on. Cellular senescence is one of the reasons why we age

In one experiment, senescent cells were removed in old mice. These old mice looked younger again: their gray fur with bald spots became shiny and black again, and the organs and other tissues of these mice could regenerate or function better compared to when they were old (R).

The mouse at the top is old, the same mouse at the bottom looks younger after senescent cell clearance (Picture by Peter De Keyser, Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging, Cell, 2017)

Other studies show that when senescent cells are destroyed, various aspects of aging can be improved (R,R,R). 

Can we reverse aging in humans?

Previous studies were done in mice. The approaches we just mentioned are currently being developed to also be used in humans, but this will take many years (probably at least 15 years before we will see these technologies being used in humans). 

So, the ultimate question is, is it possible to partially reverse aging in humans now?

Some studies have shown that it could already be possible to reverse aging in humans. At least when measured by epigenetic clocks.

Epigenetic clocks try to measure our real, biological age – so, how old you really are. One can be 50 years chronologically, but if you eat unhealthy and don’t exercise a lot, you can be biologically 58 years old.  This is what epigenetic clocks try to measure.

Epigenetic clocks look at the methylation patterns in our DNA. One way that the epigenome works is by putting small molecules, called methyl-groups, on the DNA. The more the DNA is covered with these methyl molecules, the less active the gene is (a gene is a piece of DNA containing the building instructions for a protein). Learn more about epigenetic clocks here.

One study showed that giving growth hormone, metformin and DHEA reversed the epigenetic clock a little bit, making the participants younger again. During the year that the study lasted, they reversed aging by 1.5 years (R,R).

Other studies show that lifestyle interventions, including diet, exercise and supplements can reverse aging measured by epigenetic clocks.

In one study, patients were put on a healthy diet, had to take specific supplements and exercise. After 8 weeks, their epigenetic age was reversed by almost 2 years (R).

Other studies show that people are epigenetically younger by adhering to a healthy diet, regular exercise, stress reduction, moderate alcohol consumption, and so on (R,R). 

Tips to reverse aging

Many studies show that it’s possible to reverse aging in humans through lifestyle changes and supplements. Below you can find some tips to improve your biological age (we have much more tips on this page):

  • Take supplements that improve your epigenome, like alpha-ketoglutarateglycinemicro-dosed lithiumvitamin C (all ingredients in NOVOS Core), NMN (the ingredient in NOVOS Boost). Also, take B vitamins and zinc which support the methylation process.
  • Reduce your intake of animal protein, especially processed red meat such as sausages, salami, bacon, ham, hot dogs, patés, etc.
  • Replace red meat (e.g. beef, pork, mutton, veal) with white meat (poultry), fatty fish (e.g. salmon, herring, mackerel), and meat substitutes (based on tofu, pea, or mushroom protein).
  • Consume lots of vegetables, legumes, mushrooms, fruits, nuts, seeds. Vegetables should be the basis of your diet (not potatoes, pasta, rice and bread).
  • Reduce your intake of starchy, empty-calorie foods like bread, pasta, rice, and potatoes. Replace them more with vegetables, legumes, mushrooms or quinoa.
  • Avoid sugary foods and drinks as much as possible, like sodas, fruit juices, candy, cookies, sweets, cake, pastries, doughnuts, candy bars, chocolates and so on.
  • Avoid trans fats, which can be found in fried foods, fast-food, bakery products (e.g. crackers, cookies, cakes), and vegetable shortenings.
  • Significantly reduce your intake of omega-6-fat-rich foods, like corn oil, sunflower oil, safflower oil, margarine, sesame oil, mayonnaise and most salad dressings.
    Consume more healthy fats, especially omega-3 fats, by consuming more olives, olive oil, walnuts, avocados, flax seed, chia seed, fatty fish and so on.
  • Consume foods that have come straight from nature and processed as little as possible, like foods your great-grandmother would recognize.
  • Consume a daily, freshly-made smoothie with vegetables and low-glycemic index fruits, like blueberries.
  • Eat specific foods that can slow down aging: green leafy vegetables (broccoli, spinach, kale), blueberries, dark chocolate (containing at least 70% cacao), salmon, walnuts, pomegranate, etc.
  • Don’t drink milk – milk accelerates aging.
  • Don’t drink too much alcohol: that means maximum one glass per day, ideally with alcohol-free days.
  • Hardly drink any sugary drinks (such as soda, commercial fruit juices, etc).
  • Hydrate a lot. Drink at least 1.5 of liters per day: that’s 8 glasses per day.
  • Drink lots of water. Drink green tea, white tea, ginger tea or coffee (yes, coffee can reduce the risk of various aging-related diseases). Add spices (e.g. mint), citron or NOVOS Core to add taste to your water.

We compiled 60 tips to slow down and even partially reverse aging here.

Reversing aging-related diseases

These and other studies show that aging can be reversed. And not just aging, but also various aging-related diseases at the same time. 

For example, if people adhere to a very healthy diet, many cases of type 2 diabetes can be reversed, and even atherosclerosis.

In one study, people who adhered to a more healthy diet, and had to exercise could reduce the atherosclerotic plaque in the coronary arteries of their heart, not needing a heart operation anymore (which they were recommended to undergo) (R).

And even despite these impressive results, these study interventions (read: diets) can be further improved upon. 

Even early stage Alzheimer’s disease can be reversed or substantially slowed-down if people start to eat and live healthier (R,R). We compiled various tips to reduce your risk of Alzheimer’s disease here

In other words, it’s never too late to start to eat healthy, take supplements, exercise, fast and implement many other things that can not only slow down aging, but actually make you a bit younger again!

https://novoslabs.com/reversing-aging-how-to-reverse-aging/

 Bezos, Milner Fund Altos Labs on Anti-Aging Research; New Biological Reprogramming Start-up Focuses on Age Reversal

Mark B. Sep 06, 2021

Altos Labs, an upcoming Silicon Valley company, dedicated to anti-aging research, is supposedly backed by some of the world's wealthiest.

Among the backers of the new biological reprogramming tech startup include Russian-Israeli businessman, physicist, and venture capitalist Yuri Milner and Amazon CEO Jeff Bezos. Also, according to the MIT Technology Review, the new company is already recruiting a number of university scientists to step on board, with big salaries and the promise that they could pursue their respective studies on aging and its reversal unfettered.

From Private Meeting to International Company

MIT Technology Review reports how a group of scientists attended a scientific conference right on Milner's Los Altos Hills mansion above Palo Alto to discuss how technology could be leveraged to make people younger.

Currently, Altos Labs has been incorporated in the U.K. and the U.S. earlier this year, with plans to establish several institutes such as in the Bay Area, San Diego, Cambridge, the U.K. and Japan.

So far, a few names have been attached to the project, including Juan Carlos Izpisúa Belmonte, a researcher and developmental biologist from the Salk Institute in La Jolla, California. Izpisúa Belmonte became known in the scientific community for being a part of a team that successfully implanted human cells into monkey embryos.

The study detailed in the Cell journal article "Chimeric Contribution of Human Extended Pluripotent Stem Cells to Monkey Embryos Ex Vivo" generated results that could supposedly improve understanding of early human development and improve future attempts at human chimerism, or mixing human genes with those of animals.

Also reported to join the Altos Labs team is Steve Horvath, a UCLA professor who developed a biological 'epigenetic' clock that accurately measures human aging. Known as the 'Horvath Clock,' this aging model has been described in a series of studies, including his single-author work in 2013.

Another icon in the biological reprogramming field is Shinya Yamanaka, the Japanese stem cell researcher who won a Nobel Prize for Physiology or Medicine.

One of Yamanaka's breakthroughs was that by adding a set of four proteins, the so-called 'Yamanaka factors,' cells can be 'nstructed' to return to a primitive state with the properties of stem cells. Izpisúa Belmonte used the same technology in 2016 on an entire living mouse, achieving signs of age reversal.

Quest for Youth

The key technology that Altos Labs aims to leverage is biological reprogramming, which, according to a 2011 study, is the process of 'instructing cells' or introducing materials that cause cells to revert to an earlier developmental stage, effectively reversing their entire aging process.

Other companies are also looking into biological reprogramming; chief among them Calico Labs, a life extension tech company first announced in 2013 by Google co-founder Larry Page. However, none of them has been reported to receive the same backing as Altos Labs did.

In the 2016 study by Izpisúa Belmonte's team, some of the mice exhibited different rates of biological reprogramming, with some of them developing embryonic tumors called teratomas, on top of the tissues that became younger.

"Although there are many hurdles to overcome, there is huge potential," Yamanaka told MIT Technology Review.

https://www.sciencetimes.com/articles/33282/20210906/altos-labs-new-anti-aging-research-silicon-valley-company-backed-bezos-milner.htm

Rapamycin for longevity: opinion article

 Mikhail V. Blagosklonny 1

 Go to: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/

Abstract

From the dawn of civilization, humanity has dreamed of immortality. So why didn’t the discovery of the anti-aging properties of mTOR inhibitors change the world forever? I will discuss several reasons, including fear of the actual and fictional side effects of rapamycin, everolimus and other clinically-approved drugs, arguing that no real side effects preclude their use as anti-aging drugs today. Furthermore, the alternative to the reversible (and avoidable) side effects of rapamycin/everolimus are the irreversible (and inevitable) effects of aging: cancer, stroke, infarction, blindness and premature death. I will also discuss why it is more dangerous not to use anti-aging drugs than to use them and how rapamycin-based drug combinations have already been implemented for potential life extension in humans. If you read this article from the very beginning to its end, you may realize that the time is now…: https://www.aging-us.com/

Keywords: rapamycin, rapalogs, metformin, aging, anti-aging, fasting, lifespan, health span

 How to Be 18 Years Old Again for Only $2 Million a Year

Middle-aged tech centimillionaire Bryan Johnson and his team of 30 doctors say they have a plan to reboot his body.

By Ashlee Vance

2023.25.01.

Novak Djokovic, age 35, sometimes hangs out in a pressurized egg to enrich his blood with oxygen and gives pep talks to glasses of water, hoping to purify them with positive thinking before he drinks them. Tom Brady, 45, evangelizes supposedly age-defying supplements, hydration powders and pliability spheres. LeBron James, 38, is said to spend $1.5 million a year on his body to keep Father Time at bay. While most of their contemporaries have retired, all three of these elite athletes remain marvels of fitness. But in the field of modern health science, they’re amateurs compared to Bryan Johnson….: https://www.bloomberg.com/news/features/2023-01-25/anti-aging-techniques-taken-to-extreme-by-bryan-johnson#xj4y7vzkg

Are Scientists Close to Discovering a Way to Delay Aging?

Erika P. Jul 22, 2020

Nobody can escape aging. It is associated with the dynamic changes in the biological, physiological, environmental, psychological behavioral, and social aspects of a living creature. Some results in declines in function of the sense and increased susceptibility to disease, frailty or disability.

Many scientists have already tried to develop products or methods that can delay or reverse the effects of aging. Recently, Science Times reported that researchers at USC Dornsife College of Letters, Arts and Sciences showed how mifepristone could extend the lives of Drosophila and C. elegans.

Now, scientists at the University of California San Diego (UCSD) may be one step closer to delaying the aging process.

Understanding the Aging Process of Cells 

The team of researchers studied aging in yeast cells. They chose yeast as a material of study because it can easily be manipulated. Using it, they tried to understand if different cells age at the same time, and for the same reason.

Their study yielded intriguing results. They found that although cells with the same genetic materials and within the same environment can age in "strikingly distinct ways," said the scientists who published their findings in the journal Science.

The scientists used techniques that include microfluids and computer modelling and learned that about 50% of the yeast cells aged because of a gradual decline in the cells' nucleolus- a round body situated in the nucleus of a cell.

But the other half of the yeast cells aged because there is a dysfunction of mitochondria, the powerhouse of the cell.

According to the scientists, the cells go down one of two paths, either a nuclear or mitochondrial, early in life. They continue with the route of aging until they ultimately will decline and die. The scientists performed more tests to know how the cells behaved.

"To understand how cells make these decisions, we identified the molecular processes underlying each aging route and the connections among them, revealing a molecular circuit that controls cell aging, analogous to electric circuits that control home appliances," said Nan Hao, senior author of the study and an associate professor in the division of biological sciences' molecular biology section of USCD.

Read Also: Long Life: Here's How to Extend Your Lifespan According to Science

 Designing a New Aging Path

When the team was done modeling the "aging landscape," they found that they could manipulate and optimize the process of aging by computer simulations to reprogram the master circuit of the cell and modify its DNA.

They were able to create a "novel aging route" with an extended lifespan. They believe that it could ultimately lead to the possibility of delaying the aging of humans.

"This is an aging path that never existed, but because we understand how it is regulated, we can basically design or regulate a new aging path," said Hao.

Their study raises the possibility of designing gene or chemically-based therapies to reprogram the human aging process to delay it and possibly extend the human lifespan.

The scientists are now planning to test their model in complex cells, organisms and humans, and to test how combinations of therapeutics and drugs could lead to further longevity.

https://www.sciencetimes.com/articles/26562/20200722/scientists-close-discovering-way-delay-aging.htm 

In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice

Abstract

Partial reprogramming by expression of reprogramming factors (Oct4, Sox2, Klf4 and c-Myc) for short periods of time restores a youthful epigenetic signature to aging cells and extends the life span of a premature aging mouse model. However, the effects of longer-term partial reprogramming in physiologically aging wild-type mice are unknown…: https://www.nature.com/articles/s43587-022-00183-2

Bill Gifford “Spring Chicken: Stay Young Forever (or Die Trying)”: https://www.barnesandnoble.com/w/spring-chicken-bill-gifford/1119921234 


Older Age is Associated with More Successful Aging: Role of Resilience and Depression

Abstract
Background
There is growing public health interest in understanding and promoting successful aging. While there has been some exciting empirical work on objective measures of physical health, relatively little published research combines physical, cognitive, and psychological assessments in large, randomly selected, community-based samples to assess self-rated successful aging (SRSA)….
Conclusions
Resilience and depression had a significant association with SRSA with effect sizes comparable to that for physical health. While no causality can be inferred from cross-sectional data, increasing resilience and reducing depression might have as strong effects on successful aging as reducing physical disability, suggesting an important role for psychiatry in promoting successful aging.

Tibetan Secrets of Youth and Vitality: How to Look and Feel Younger Using Five Ancient Rites for Stimulating your Energy Centres

by Peter Kelder

Well versed in the Tibetan Rites of Rejuvenation since the 1930s, Peter Kelder is alive and well, living in California. He is the author of Ancient Secrets of the Fountain of Youth.

https://www.goodreads.com/book/show/21016130-tibetan-secrets-of-youth-and-vitality


Reversal of epigenetic aging and immunosenescent trends in humans

First published: 08 September 2019

Abstract

Epigenetic “clocks” can now surpass chronological age in accuracy for estimating biological age. Here, we use four such age estimators to show that epigenetic aging can be reversed in humans. Using a protocol intended to regenerate the thymus, we observed protective immunological changes, improved risk indices for many agerelated diseases, and a mean epigenetic age approximately 1.5 years less than baseline after 1 year of treatment (−2.5year change compared to no treatment at the end of the study). The rate of epigenetic aging reversal relative to chronological age accelerated from −1.6 year/year from 0–9 month to −6.5 year/year from 9–12 month. The GrimAge predictor of human morbidity and mortality showed a 2year decrease in epigenetic vs. chronological age that persisted six months after discontinuing treatment. This is to our knowledge the first report of an increase, based on an epigenetic age estimator, in predicted human lifespan by means of a currently accessible aging intervention.
1 INTRODUCTION

Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells : a prospective trial

Abstract

Introduction: Aging is characterized by the progressive loss of physiological capacity. At the cellular level, two key hallmarks of the aging process include telomere length (TL) shortening and cellular senescence. Repeated intermittent hyperoxic exposures, using certain hyperbaric oxygen therapy (HBOT) protocols, can induce regenerative effects which normally occur during hypoxia. The aim of the current study was to evaluate whether HBOT affects TL and senescent cell concentrations in a normal, non-pathological, aging adult population.

Methods: Thirty-five healthy independently living adults, aged 64 and older, were enrolled to receive 60 daily HBOT exposures. Whole blood samples were collected at baseline, at the 30th and 60th session, and 1-2 weeks following the last HBOT session. Peripheral blood mononuclear cells (PBMCs) telomeres length and senescence were assessed.

Results: Telomeres length of T helper, T cytotoxic, natural killer and B cells increased significantly by over 20% following HBOT. The most significant change was noticed in B cells which increased at the 30th session, 60th session and post HBOT by 25.68%±40.42 (p=0.007), 29.39%±23.39 (p=0.0001) and 37.63%±52.73 (p=0.007), respectively.

There was a significant decrease in the number of senescent T helpers by -37.30%±33.04 post-HBOT (P<0.0001). T-cytotoxic senescent cell percentages decreased significantly by -10.96%±12.59 (p=0.0004) post-HBOT.

In conclusion, the study indicates that HBOT may induce significant senolytic effects including significantly increasing telomere length and clearance of senescent cells in the aging populations.

https://www.aging-us.com/article/202188/text

Nature Aging

 23 November 2020

Sestrin is a key regulator of stem cell function and lifespan in response to dietary amino acids…: https://www.nature.com/nataging

Reprogramming to recover youthful epigenetic information and restore vision

Abstract

Ageing is a degenerative process that leads to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise that disrupts gene expression patterns, leading to decreases in tissue function and regenerative capacity1,2,3. Changes to DNA methylation patterns over time form the basis of ageing clocks4, but whether older individuals retain the information needed to restore these patterns—and, if so, whether this could improve tissue function—is not known. Over time, the central nervous system (CNS) loses function and regenerative capacity5,6,7. Using the eye as a model CNS tissue, here we show that ectopic expression of Oct4 (also known as Pou5f1), Sox2 and Klf4 genes (OSK) in mouse retinal ganglion cells restores youthful DNA methylation patterns and transcriptomes, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice. The beneficial effects of OSK-induced reprogramming in axon regeneration and vision require the DNA demethylases TET1 and TET2. These data indicate that mammalian tissues retain a record of youthful epigenetic information—encoded in part by DNA methylation—that can be accessed to improve tissue function and promote regeneration in vivo.

https://www.nature.com/articles/s41586-020-2975-4

A genome-wide CRISPR-based screen identifies KAT7 as a driver of cellular senescence

Slowing cellular senescence

Whereas cellular senescence is known to promote aging, many of the mechanisms controlling this process remain poorly understood. Using human mesenchymal precursor cells (hMPCs) carrying pathogenic mutations of the premature aging diseases Werner syndrome and Hutchinson-Gilford progeria syndrome, the authors conducted a genome-wide CRISPR-Cas9–based screen to identify genes that could affect cellular senescence. They identified KAT7, a histone acetyltransferase gene, as a driver of senescence. Inactivation of Kat7 in mice aging normally and in prematurely aging progeroid mice extended their life span. Although KAT7 requires further study in other cell types, these experiments highlight the utility of genome-wide CRISPR-Cas9 screens and shed further light on mechanisms controlling senescence.

Abstract

Understanding the genetic and epigenetic bases of cellular senescence is instrumental in developing interventions to slow aging. We performed genome-wide CRISPR-Cas9–based screens using two types of human mesenchymal precursor cells (hMPCs) exhibiting accelerated senescence. The hMPCs were derived from human embryonic stem cells carrying the pathogenic mutations that cause the accelerated aging diseases Werner syndrome and Hutchinson-Gilford progeria syndrome. Genes whose deficiency alleviated cellular senescence were identified, including KAT7, a histone acetyltransferase, which ranked as a top hit in both progeroid hMPC models. Inactivation of KAT7 decreased histone H3 lysine 14 acetylation, repressed p15INK4b transcription, and alleviated hMPC senescence. Moreover, lentiviral vectors encoding Cas9/sg-Kat7, given intravenously, alleviated hepatocyte senescence and liver aging and extended life span in physiologically aged mice as well as progeroid Zmpste24−/− mice that exhibit a premature aging phenotype. CRISPR-Cas9–based genetic screening is a robust method for systematically uncovering senescence genes such as KAT7, which may represent a therapeutic target for developing aging interventions.

https://stm.sciencemag.org/content/13/575/eabd2655

First hint that body’s ‘biological age’ can be reversed


In a small trial, drugs seemed to rejuvenate the body’s ‘epigenetic clock’, which tracks a person’s biological age…: https://www.nature.com/articles/d41586-019-02638-w


Longevity Promotion: Multidisciplinary Perspectives

author | Ilia Stambler  year published |2017


    This book considers the multidisciplinary aspects of longevity promotion, from the advocacy, historical, philosophical and scientific perspectives. The first part on longevity advocacy includes examples of pro-longevity campaigns, outreach materials, frequent debates and policy suggestions and frameworks that may assist in the promotion of research and development for healthy longevity. The second part on longevity history includes analyses of the definition of life-extensionism as a social and intellectual movement, the dialectics of reductionism vs. holism and the significance of the concept of constancy in the history of life extension research, an historical overview of evolutionary theories of aging, and a tribute to one of the founding figures of modern longevity science. The third part on longevity philosophy surveys the aspirations and supportive arguments for increasing healthy longevity in the philosophical and religious traditions of ancient Greece, India, the Middle East, in particular in Islam and Judaism, and the Christian tradition. Finally, the fourth part on longevity science includes brief discussions of some of the scientific issues in life extension research, in particular regarding some potential interventions to ameliorate degenerative aging, some methodological issues with diagnosing and treating degenerative aging as a medical condition, the application of information theory for aging and longevity research, some potential physical means for life extension, and some resources for further consideration. These discussions are in no way exhaustive, but are intended to simulate additional interest, consultation and study of longevity science and its social and cultural implications. It is hoped that this book will contribute to broadening, diversifying and strengthening the academic and public deliberation on the prospects of healthy life extension for the entire population. The setting and careful consideration of a goal may be seen as a first step toward its accomplishment.

PUBLIC RELEASE: 3-APR-2017
Reversing aging now possible!
World's first to confirm that as cell aging progresses
DGIST (DAEGU GYEONGBUK INSTITUTE OF SCIENCE AND TECHNOLOGY)
    DGIST's research team discovered substances that can induce reversible aging* recovery and identified an aging recovery mechanism using these substances.
Aging is a phenomenon in which a cell's ability to divide and grow deteriorates as it gets older, and this causes degradation of the body and senile diseases. The inhibition and recovery of aging is an instinctive desire of humans; thus, it is a task and challenge of biologists to identify substances that control aging and analyze aging mechanisms.
DGIST's research team have been conducting research to reverse the aging process by shifting the existing academia's 'irreversibility of aging' paradigm, which means aging cannot be reversed.
To reverse the aging process, the research team searched for factors that could control aging and tried to discover substances that could restore cell division capacity. As a result, it was confirmed that KU-60019, an inhibitor of ATM protein, which is a phosphorylation enzyme, recovers the functions of aging cells through activation of lysosomal functions and induction of cell proliferation.
The degradation of lysosomes, which are intracellular organelles responsible for autophagy and decomposition of biopolymers such as proteins and lipids in the cell, leads to cell senescence by accumulating biomolecules that must be removed in cells and causes instability of the metabolism such as removal of dysfunctional mitochondria that do not function.
The research team was the world's first to confirm that as cell aging progresses, the vacuolar ATPase (v-ATPase) protein involved in the lysosomal activity regulation is phosphorylated by the ATM protein, and the binding force between the units constituting the v-ATPase is weakened, so consequently the function of lysosomes deteriorates.
In addition, the team has proven that the reversible recovery of aging is possible through its experiment that shows the regulation of ATM protein activation by KU-60019 substances induces the reduction of phosphorylation of v-ATPase, thereby inducing recovery of mitochondrial function and functional recovery of the lysosome and autophagy system as well as promoting wound healing in aging animal models.
DGIST Chair Professor Park SangChul said, "The significance and implication of this study is that it is possible to reverse the recovery of aging cells by inhibiting and restoring the degradation of lysosomal function. In the future, we will continue to conduct studies that extend the life expectancy of human beings by verifying and validating efficacy and safety through aging animal models."
* Reversible aging: In a chemical reaction, when two substances are reacted at a specific concentration, pressure, temperature, etc., and a product is made, the reaction in which the first two substances are formed after reacting this product is called a reversible reaction. On the other hand, reactions that occur only in one direction are called irreversible reactions. Instead of seeing the aging of living organisms as they grow older as irreversible and inevitable, they see it as reversible and restorable; thus, the term 'reversible aging' is used to denote such a reaction.
Scientists reverse aging in mice by repairing damaged DNA
Could lead to an anti-aging drug that counters damage from old age, cancer, and radiation
March 26, 2017
A research team led by Harvard Medical School professor of genetics David Sinclair, PhD, has made a discovery that could lead to a revolutionary new drug that allows cells to repair DNA damaged by aging, cancer, and radiation.
In a paper published in the journal Science on Friday (March 24), the scientists identified a critical step in the molecular process related to DNA damage.
The researchers found that a compound known as NAD (nicotinamide adenine dinucleotide), which is naturally present in every cell of our body, has a key role as a regulator in protein-to-protein interactions that control DNA repair. In an experiment, they found that treating mice with a NAD+ precursor called NMN (nicotinamide mononucleotide) improved their cells’ ability to repair DNA damage.
“The cells of the old mice were indistinguishable from the young mice, after just one week of treatment,” said senior author Sinclair.
Disarming a rogue agent: When the NAD molecule (red) binds to the DBC1 protein (beige), it prevents DBC1 from attaching to and incapacitating a protein (PARP1) that is critical for DNA repair. (credit: David Sinclair)
Human trials of NMN therapy will begin within the next few months to “see if these results translate to people,” he said. A safe and effective anti-aging drug is “perhaps only three to five years away from being on the market if the trials go well.”
What it means for astronauts, childhood cancer survivors, and the rest of us
The researchers say that in addition to reversing aging, the DNA-repair research has attracted the attention of NASA. The treatment could help deal with radiation damage to astronauts in its Mars mission, which could cause muscle weakness, memory loss, and other symptoms (see “Mars-bound astronauts face brain damage from galactic cosmic ray exposure, says NASA-funded study“), and more seriously, leukemia cancer and weakened immune function (see “Travelers to Mars risk leukemia cancer, weakend immune function from radiation, NASA-funded study finds“).
The treatment could also help travelers aboard aircraft flying across the poles. A 2011 NASA study showed that passengers on polar flights receive about 12 percent of the annual radiation limit recommended by the International Committee on Radiological Protection.
The other group that could benefit from this work is survivors of childhood cancers, who are likely to suffer a chronic illness by age 45, leading to accelerated aging, including cardiovascular disease, Type 2 diabetes, Alzheimer’s disease, and cancers unrelated to the original cancer, the researchers noted.
For the past four years, Sinclair’s team has been working with spinoff MetroBiotech on developing NMN as a drug. Sinclair previously made a link between the anti-aging enzyme SIRT1 and resveratrol. “While resveratrol activates SIRT1 alone, NAD boosters [like NMN] activate all seven sirtuins, SIRT1-7, and should have an even greater impact on health and longevity,” he says.
Sinclair is also a professor at the University of New South Wales School of Medicine in Sydney, Australia.


Abstract of A conserved NAD+ binding pocket that regulates protein-protein interactions during aging
DNA repair is essential for life, yet its efficiency declines with age for reasons that are unclear. Numerous proteins possess Nudix homology domains (NHDs) that have no known function. We show that NHDs are NAD+ (oxidized form of nicotinamide adenine dinucleotide) binding domains that regulate protein-protein interactions. The binding of NAD+to the NHD domain of DBC1 (deleted in breast cancer 1) prevents it from inhibiting PARP1 [poly(adenosine diphosphate–ribose) polymerase], a critical DNA repair protein. As mice age and NAD+ concentrations decline, DBC1 is increasingly bound to PARP1, causing DNA damage to accumulate, a process rapidly reversed by restoring the abundance of NAD+. Thus, NAD+ directly regulates protein-protein interactions, the modulation of which may protect against cancer, radiation, and aging.
references:
Topics: Biomed/Longevity | Biotech


Mitochondria-targeted hydrogen sulfide attenuates endothelial senescence by selective induction of splicing factors HNRNPD and SRSF2
Eva Latorre 1 , Roberta Torregrossa 1 , Mark E. Wood 2 , Matthew Whiteman 1 ,Lorna W. Harries 1
  • 1 University of Exeter Medical School, University of Exeter, UK
  • 2 College of Life and Environmental Sciences, University of Exeter, UK
published: July 19, 2018
Abstract
Cellular senescence is a key driver of ageing, influenced by age-related changes to the regulation of alternative splicing. Hydrogen sulfide (H2S) has similarly been described to influence senescence, but the pathways by which it accomplishes this are unclear.
We assessed the effects of the slow release H2S donor Na-GYY4137 (100 µg/ml), and three novel mitochondria-targeted H2S donors AP39, AP123 and RT01 (10 ng/ml) on splicing factor expression, cell proliferation, apoptosis, DNA replication, DNA damage, telomere length and senescence-related secretory complex (SASP) expression in senescent primary human endothelial cells.
All H2S donors produced up to a 50% drop in senescent cell load assessed at the biochemical and molecular level. Some changes were noted in the composition of senescence-related secretory complex (SASP); IL8 levels increased by 24% but proliferation was not re-established in the culture as a whole. Telomere length, apoptotic index and the extent of DNA damage were unaffected. Differential effects on splicing factor expression were observed depending on the intracellular targeting of the H2S donors. Na-GYY4137 produced a general 1.9 – 3.2-fold upregulation of splicing factor expression, whereas the mitochondria-targeted donors produced a specific 2.5 and 3.1-fold upregulation of SRSF2 and HNRNPD splicing factors only. Knockdown of SRSF2 or HNRNPD genes in treated cells rendered the cells non-responsive to H2S, and increased levels of senescence by up to 25% in untreated cells.
Our data suggest that SRSF2 and HNRNPD may be implicated in endothelial cell senescence, and can be targeted by exogenous H2S. These molecules may have potential as moderators of splicing factor expression and senescence phenotypes.
Introduction
Ageing is characterised by a progressive decline of physiological function accompanied by increased incidence of age-related disease. The biochemical and functional pathways most dysregulated by age in the human peripheral blood transcriptome are enriched for transcripts encoding the regulatory machinery that governs splice site choice [1]. Changes in splicing regulation have also been linked with lifespan in both mammalian and invertebrate model systems [2,3]. Evidence that these changes are functional is provided by the observation that large-scale dysregulation of patterns of alternative splicing is characteristic of many age related diseases such as Alzheimer’s disease [4], Parkinson’s disease [5] and cancer [6]. These observations highlight the importance of maintenance of correct splicing regulation for health throughout the life course [7].
The accumulation of senescent cells is emerging as an important driving factor of the ageing process in multiple species [811]. Senescent cells do not divide, are viable and metabolically active, but have altered physiology. This includes the secretion of the SASP, a cocktail of pro-inflammatory cytokines and tissue remodelling factors that induces senescence in neighbouring cells in a paracrine manner [12]. Senescent cells in endothelium and cardiac tissues have been associated with increased cardiovascular dysfunction [13]. Senescence of cardiomyocytes and endothelial cells has been associated with hardening of the heart muscle and stiffening of the vascular wall, resulting in angina, dyspnea and heart failure [14]. Endothelial cell senescence has also been associated with vascular dysfunction and increased vascular risk [15]. Perhaps most persuasively, targeted removal of senescent cells in transgenic mouse models has been shown to result in improvements to multiple ageing phenotypes [16,17]. Senescent cells also show dysregulation of splicing regulator expression in vitro [18,19], and restoration of splicing factor expression to levels comparable with those seen in younger cells has recently been demonstrated to be associated with reversal of multiple senescence phenotypes in senescent human primary fibroblasts [20].
There is now enormous interest in compounds with the potential to kill senescent cells (senolysis) or ameliorate their effects (senostasis). The endogenous gaseous mediator hydrogen sulfide (H2S) has been described to exert a protective effect against cellular senescence and ageing phenotypes [2123], and accordingly, to have protective effects against several age related diseases [2427], although many of these studies have been carried out using non-physiological conditions, using very high levels of H2S. Plasma H2S level declines with age [28], is associated with hypertension in animals and humans [21,29] and shows a significant inverse correlation with severity of coronary heart disease [30]. Disruption of H2S homeostasis may also contribute to the pathogenesis of atherosclerosis [31], where H2S could play an anti-atherogenic role [32]. Conversely, supplementation of animals with an exogenous source of H2S reverses the disease phenotype [33]. H2S has been proposed to prevent cell damage under stress in part due to persulfidation of target proteins [34]. These observations suggest that H2S could represent a potential new intervention for ageing and age-related disease.
Here, we aimed to assess the effect of the H2S donor Na-GYY4137 [35,36], and since mitochondria are a source and a target of H2S, three novel H2S donors, AP39, AP123 and RT01 previously demonstrated to be targeted specifically to the mitochondria [3739], on splicing regulatory factor expression and cell senescence phenotypes in senescent primary human endothelial cells. Treatment with Na-GYY4137 resulted in an almost global upregulation of splicing factor expression in treated cells consistent with that observed with resveratrol analogues in our previous work [20]. Conversely, H2S donors targeted to the mitochondria also resulted in rescue from senescence but each demonstrated a very specific upregulation of transcripts encoding the splicing activator protein SRSF2 and the splicing inhibitor protein HNRNPD. Abolition of either SRSF2 or HNRNPD expression in primary endothelial cells by morpholino technologies in the absence of any treatment resulted in increased levels of cellular senescence. None of the H2S donors were able to reduce senescent cell load in cells in which SRSF2 or HNRNPD expression had been abrogated. These data strongly suggest that mitochondria-targeted H2S is capable of rescuing senescence phenotypes in endothelial cells through mechanisms that specifically involve SRSF2 and HNRNPD.
Results: http://www.aging-us.com/article/101500/text


β-Hydroxybutyrate Prevents Vascular Senescence through hnRNP A1-Mediated Upregulation of Oct4
Published:September 06, 2018DOI:https://doi.org/10.1016/j.molcel.2018.07.036
Highlights
  • β-hydroxybutyrate prevents the vascular cell senescence
  • β-hydroxybutyrate upregulates Oct4 expression via interacting with hnRNP A1
  • Oct4-mediated quiescence is able to attenuate hallmarks of senescence
  • Circulating β-hydroxybutyrate alleviates the senescence of mouse aorta
Summary

β-hydroxybutyrate (β-HB) elevation during fasting or caloric restriction is believed to induce anti-aging effects and alleviate aging-related neurodegeneration. However, whether β-HB alters the senescence pathway in vascular cells remains unknown. Here we report that β-HB promotes vascular cell quiescence, which significantly inhibits both stress-induced premature senescence and replicative senescence through p53-independent mechanisms. Further, we identify heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) as a direct binding target of β-HB. β-HB binding to hnRNP A1 markedly enhances hnRNP A1 binding with Octamer-binding transcriptional factor (Oct) 4 mRNA, which stabilizes Oct4 mRNA and Oct4 expression. Oct4 increases Lamin B1, a key factor against DNA damage-induced senescence. Finally, fasting and intraperitoneal injection of β-HB upregulate Oct4 and Lamin B1 in both vascular smooth muscle and endothelial cells in mice in vivo. We conclude that β-HB exerts anti-aging effects in vascular cells by upregulating an hnRNP A1-induced Oct4-mediated Lamin B1 pathway. https://www.cell.com/molecular-cell/fulltext/S1097-2765(18)30605-1 


Prospectively Isolated Tetraspanin+ Neoblasts Are Adult Pluripotent Stem Cells Underlying Planaria Regeneration

Published: June 14, 2018DOI:https://doi.org/10.1016/j.cell.2018.05.006
Highlights
piwi-1 RNA and protein expression defined spectrum of functional neoblast states
scRNA-seq defined 12 neoblast sub-types; sub-type Nb2 contains pluripotent stem cells
Transplantation of single TSPAN-1 + Nb2 cells rescued lethally irradiated animals
Nb2 transcriptome differs during homeostasis, sublethal irradiation, and regeneration

Summary

Proliferating cells known as neoblasts include pluripotent stem cells (PSCs) that sustain tissue homeostasis and regeneration of lost body parts in planarians. However, the lack of markers to prospectively identify and isolate these adult PSCs has significantly hampered their characterization. We used single-cell RNA sequencing (scRNA-seq) and single-cell transplantation to address this long-standing issue. Large-scale scRNA-seq of sorted neoblasts unveiled a novel subtype of neoblast (Nb2) characterized by high levels of PIWI-1 mRNA and protein and marked by a conserved cell-surface protein-coding gene, tetraspanin 1 ( tspan-1). tspan-1-positive cells survived sub-lethal irradiation, underwent clonal expansion to repopulate whole animals, and when purified with an anti-TSPAN-1 antibody, rescued the viability of lethally irradiated animals after single-cell transplantation. The first prospective isolation of an adult PSC bridges a conceptual dichotomy between functionally and molecularly defined neoblasts, shedding light on mechanisms governing in vivo pluripotency and a source of regeneration in animals…:
https://www.cell.com/cell/fulltext/S0092-8674(18)30583-X



Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline-albumin
Published: May 30, 2020
Abstract

Heterochronic blood sharing rejuvenates old tissues, and most of the studies on how this works focus on young plasma, its fractions, and a few youthful systemic candidates. However, it was not formally established that young blood is necessary for this multi-tissue rejuvenation. Here, using our recently developed small animal blood exchange process, we replaced half of the plasma in mice with saline containing 5% albumin (terming it a “neutral” age blood exchange, NBE) thus diluting the plasma factors and replenishing the albumin that would be diminished if only saline was used. Our data demonstrate that a single NBE suffices to meet or exceed the rejuvenative effects of enhancing muscle repair, reducing liver adiposity and fibrosis, and increasing hippocampal neurogenesis in old mice, all the key outcomes seen after blood heterochronicity. Comparative proteomic analysis on serum from NBE, and from a similar human clinical procedure of therapeutic plasma exchange (TPE), revealed a molecular re-setting of the systemic signaling milieu, interestingly, elevating the levels of some proteins, which broadly coordinate tissue maintenance and repair and promote immune responses. Moreover, a single TPE yielded functional blood rejuvenation, abrogating the typical old serum inhibition of progenitor cell proliferation. Ectopically added albumin does not seem to be the sole determinant of such rejuvenation, and levels of albumin do not decrease with age nor are increased by NBE/TPE. A model of action (supported by a large body of published data) is that significant dilution of autoregulatory proteins that crosstalk to multiple signaling pathways (with their own feedback loops) would, through changes in gene expression, have long-lasting molecular and functional effects that are consistent with our observations. This work improves our understanding of the systemic paradigms of multi-tissue rejuvenation and suggest a novel and immediate use of the FDA approved TPE for improving the health and resilience of older people.


Transcend: Nine Steps to Living Well Forever

In 2004, Ray Kurzweil and Terry Grossman, MD, published Fantastic Voyage: Live Long Enough to Live Forever. Their groundbreaking book marshaled thousands of scientific studies to make the case that new developments in medicine and technology will allow us to radically extend our life expectancies and slow down the aging process. Soon, our notion of what it means to be a 55-year-old will be as outdated as an eight-track tape player.
TRANSCEND: Nine Steps to Living Well Forever presents a practical, enjoyable program so that readers can live long enough (and remain healthy long enough) to take full advantage of the biotech and nanotech advances that have already begun and will be occurring at an accelerating pace during the years ahead. To help readers remember the nine key components of the program, Ray and Terry have arranged them into a mnemonic:  Talk with your doctor Relaxation Assessment Nutrition Supplementation Calorie reduction Exercise New technologies Detoxification  This easy-to-follow program will help readers transcend the boundaries of our genetic legacy and live long enough to live forever. 





Key molecule of aging discovered

GERMAN CANCER RESEARCH CENTER (DEUTSCHES KREBSFORSCHUNGSZENTRUM, DKFZ)
Every cell and every organism ages sooner or later. But why is this so? Scientists at the German Cancer Research Center in Heidelberg have now discovered for the first time a protein that represents a central switching point in the aging process. It controls the life span of an individual - from the fly to the human being. This opens up new possibilities for developing therapies against age-related diseases.
Oxidative stress causes cells and entire organisms to age. If reactive oxygen species accumulate, this causes damage to the DNA as well as changes in the protein molecules and lipids in the cell. The cell ultimately loses its functionality and dies. Over time, the tissue suffers and the body ages. "The theory of oxidative stress or the accumulation of reactive oxygen species as the cause of aging has existed since the 1950s," says Peter Krammer of the German Cancer Research Center (DKFZ). "So far, however, the details of this process were unclear."
In fact, reactive oxygen species do more than just damage the body. For example, they are essential for the T-cells of the immune system to become active. DKFZ researchers led by Krammer and Karsten Gülow* have now discovered the key regulator that is responsible for shifting the sensitive balance from vital to harmful amounts of reactive oxygen molecules and thus accelerating the aging process: A protein molecule called TXNIP (thioredoxin-interacting protein).
One way in which the body disposes of harmful reactive oxygen species is their conversion by the enzyme thioredoxin-1 (TRX-1). TRX-1 has been proven to play a role in protecting DNA from oxidative stress and slowing down aging processes. Its antagonist TXNIP inhibits thioredoxin-1 and thus ensures that the reactive oxygen molecules are retained.
The DKFZ researchers led by Krammer and Gülow now wanted to know whether more TXNIP is formed in the body with increasing age, thereby undermining the protective mechanism against oxidative stress. To this end, they first compared T cells from the blood of a group of over 55-year-old volunteers with the T cells of younger blood donors, who were between 20 and 25 years old. In fact, it turned out that the cells of older subjects produce significantly more TXNIP. The DKFZ scientists have also observed similar findings in other human cell and tissue types.
The researchers also found out that more TXNIP is produced in the fly Drosophila with increasing age. In order to test whether TXNIP is actually responsible for aging, they bred flies that produce significantly more TXNIP than their relatives as well as flies in which TXNIP synthesis is greatly reduced. "Flies that produced more TXNIP lived on average much shorter, while flies with less TXNIP had a longer average life," sums up Tina Oberacker, who was responsible for the fly experiments.
"TRX-1 and its opponent TXNIP are highly conserved in the course of evolution; they hardly differ between flies and humans," explains Krammer. It can therefore be assumed that the two proteins perform similar functions in flies and humans. If more TXNIP is produced with increasing age, this means that TRX is gradually switched off with its protection function. This leads to more oxidative stress, which damages cells and tissue and eventually causes them to die.
Krammer is convinced that TXNIP is a key regulator for aging. "Scientists have found hundreds of genes that are somehow related to the aging process," says the DKFZ researcher summarizing the results. "But it is enough to switch off TXNIP to delay aging. Similarly, aging can be accelerated if we get the cells to produce TXNIP. "And that makes it an interesting candidate to intervene in the aging process in the future."
###
The research was funded by the European Union and the Wilhelm Sander Foundation.
Tina Oberacker, Jörg Bajorat, Sabine Ziola, Anne Schroeder, Daniel Röth, Lena Kastl, Bruce A. Edgar, Wolfgang Wagner, Karsten Gülow, Peter H. Krammer: Enhanced expression of thioredoxin interacting protein regulates oxidative DNA damage and aging. FEBS Letters, 2018, doi: 10.1002/1873-3468.13156
*Current affiliation: University of Regensburg
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.
https://www.eurekalert.org/pub_releases/2018-06/gcrc-kmo062018.php


Ageotypes’ provide window into how individuals age, Stanford study reports
Stanford scientists have identified specific biological pathways along which individuals age over time....: https://med.stanford.edu/news/all-news/2020/01/_ageotypes_-provide-window-into-how-individuals-age--stanford-st.html

Personal aging markers and ageotypes revealed by deep longitudinal profiling

Small molecule cognitive enhancer reverses age-related memory decline in mice

Abstract

With increased life expectancy age-associated cognitive decline becomes a growing concern, even in the absence of recognizable neurodegenerative disease. The integrated stress response (ISR) is activated during aging and contributes to age-related brain phenotypes. We demonstrate that treatment with the drug-like small-molecule ISR inhibitor ISRIB reverses ISR activation in the brain, as indicated by decreased levels of activating transcription factor 4 (ATF4) and phosphorylated eukaryotic translation initiation factor eIF2. Furthermore, ISRIB treatment reverses spatial memory deficits and ameliorates working memory in old mice. At the cellular level in the hippocampus, ISR inhibition i) rescues intrinsic neuronal electrophysiological properties, ii) restores spine density and iii) reduces immune profiles, specifically interferon and T cell-mediated responses. Thus, pharmacological interference with the ISR emerges as a promising intervention strategy for combating age-related cognitive decline in otherwise healthy individuals.: https://elifesciences.org/articles/62048



Chemical Conversion of Human Fetal Astrocytes into Neurons through Modulation of Multiple Signaling Pathways
Highlights
Chemical reprogramming of human astrocytes into neurons with three to four small molecules
Notch/GSK-3/TGF-β/BMP pathways are critical for astrocyte-to-neuron conversion
Human fetal astrocytes are chemically converted into glutamatergic neurons
In vivo administration of four core drugs increases hippocampal adult neurogenesis
Summary
We have previously developed a cocktail of nine small molecules to convert human fetal astrocytes into neurons, but a nine-molecule recipe is difficult for clinical applications. Here, we identify a chemical formula with only three to four small molecules for astrocyte-to-neuron conversion. We demonstrate that modulation of three to four signaling pathways among Notch, glycogen synthase kinase 3, transforming growth factor β, and bone morphogenetic protein pathways is sufficient to change an astrocyte into a neuron. The chemically converted human neurons can survive >7 months in culture, fire repetitive action potentials, and display robust synaptic burst activities. Interestingly, cortical astrocyte-converted neurons are mostly glutamatergic, while midbrain astrocyte-converted neurons can yield some GABAergic neurons in addition to glutamatergic neurons. When administered in vivo through intracranial or intraperitoneal injection, the four-drug combination can significantly increase adult hippocampal neurogenesis. Together, human fetal astrocytes can be chemically converted into functional neurons using three to four small molecules, bringing us one step forward for developing future drug therapy….:


An evolutionary transcriptomics approach links CD36 to membrane remodeling in replicative senescence

Abstract
Cellular senescence, the irreversible ceasing of cell division, has been associated with organismal aging, prevention of cancerogenesis, and developmental processes. As such, the evolutionary basis and biological features of cellular senescence remain a fascinating area of research. In this study, we conducted comparative RNAseq experiments to detect genes associated with replicative senescence in two different human fibroblast cell lines and at different time points. We identified 841 and 900 genes (core senescence-associated genes) that are significantly up- and downregulated in senescent cells, respectively, in both cell lines. Our functional enrichment analysis showed that downregulated core genes are primarily involved in cell cycle processes while upregulated core gene enrichment indicated various lipid-related processes. We further demonstrated that downregulated genes are significantly more conserved than upregulated genes. Using both transcriptomics and genetic variation data, we identified one of the upregulated, lipid metabolism genes, CD36, as an outlier. We found that overexpression of CD36 induces a senescence-like phenotype and, further, the media of CD36-overexpressing cells alone can induce a senescence-like phenotype in proliferating young cells. Moreover, we used a targeted lipidomics approach and showed that phosphatidylcholines accumulate during replicative senescence in these cells, suggesting that upregulation of CD36 could contribute to membrane remodeling during senescence. Overall, these results contribute to the understanding of evolution and biology of cellular senescence and identify several targets and questions for future studies.



Anti-aging stem cell treatment proves successful in early human trials

Rich Haridy October 24th, 2017
A landmark stem cell therapy to treat frailty in senior citizens is all set to move into the final phase of human clinical trials(Credit: vshivkova/Depositphotos)
The results of two human clinical trials into a stem cell therapy that can reverse symptoms of age-associated frailty have been published, and the indications are that this landmark treatment is both safe and strikingly effective in tackling key factors in aging.
Scientists have been making significant headway recently, studying a variety of anti-aging targets from discovering a protein that can restore hair and improve fitness in old mice to revealing how fecal transplants increase the lifespan of some fish. But the arena of stem cell transplantation has offered some of the most exciting anti-aging research outcomes.
Mesenchymal stem cells (MSCs) are a particular type of adult stem cell generating a great deal of interest in the world of science. MSCs are currently being trailed as treatment for no less than a dozen different types of pathological conditions from cancer to heart disease.
This new MSC treatment is targeted at reducing the effects of frailty on senior citizens. This is the first anti-aging stem cell treatment directed specifically at the problem of age-associated frailty to move close to a final FDA approval stage.
The treatment derives human mesenchymal stem cells from adult donor bone marrow and in these clinical trials involves a single infusion in patients with an average age of 76. Both Phase 1 and Phase 2 human trials have demonstrated the treatment to have no adverse health effects.
Although the two human trials were ostensibly designed to just demonstrate safety they do offer remarkable results in efficacy as well, paving the way for larger, Phase 3 clinical trials.
In the first trial 15 frail patients received a single MSC infusion collected from bone marrow donors aged between 20 and 45 years old. Six months later all patients demonstrated improved fitness outcomes, tumor necrosis factor levels and overall quality of life.
The second trial was a randomized, double blind study with placebo group. Again no adverse affects were reported and physical improvements were noted by the researchers as "remarkable".
"There are always caveats associated with interpreting efficacy in small numbers of subjects, yet it is remarkable that a single treatment seems to have generated improvement in key features of frailty that are sustained for many months," writes David G. Le Couter and colleagues in a guest editorial in The Journals of Gerontology praising the research.
The next stage for the research is to move into an expanded Phase 2b clinical trial involving 120 subjects across 10 locations. After that a final, large randomized Phase 3 clinical trial will be the only thing holding the treatment back from final public approval.
"With the aging of the population, stem cells hold great promise to treat aging-related disability and frailty, improving physical capacity and quality of life," says one of the scientists working on the project Joshua M. Hare, Director of the Interdisciplinary Stem Cell Institute at the University of Miami Miller School of Medicine.
"There is no FDA approved treatment for aging frailty and an enormous unmet need that will only increase with the changing demographics."

Source: University of Miami, Miller School of Medicine

Stem cell study may result in stronger muscles in old age

February 26, 2018, Karolinska Institutet
Muscular function declines with age. A new study by researchers at Karolinska Institutet in Sweden shows how an unexpectedly high number of mutations in the stem cells of muscles impair cell regeneration. This discovery may result in new medication to build stronger muscles throughout aging. The study is published in Nature Communications.
It has already been established that natural aging impairs the function of skeletal muscles. We also know that the number and the activity of the muscles' stem cells decline with age. However, the reasons are not fully understood. In a new study, researchers at Karolinska Institutet have investigated the number of mutations that accumulate in the muscle's stem cells (satellite cells).
"What is most surprising is the high number of mutations. We have seen how a healthy 70-year-old has accumulated more than 1,000 mutations in each stem cell in the muscle, and that these mutations are not random, but there are certain regions that are better protected," says Maria Eriksson, professor in the Department of Biosciences and Nutrition at Karolinska Institutet.
The mutations occur during natural cell division, and the regions that are protected are those that are important for the function or survival of the cells. Nonetheless, the researchers were able to identify that this protection declines with age.
"We can demonstrate that this protection diminishes the older you become, indicating an impairment in the cell's capacity to repair their DNA. And this is something we should be able to influence with new drugs," explains Maria Eriksson.
The researchers have benefited from new methods to complete the study. The study was performed using single stem cells cultivated to provide sufficient DNA for whole genome sequencing. "We achieved this in the skeletal muscle tissue, which is absolutely unique. We have also found that there is very little overlap of mutations, despite the cells being located close to each other, representing an extremely complex mutational burden," explains the study's first author, Irene Franco, Postdoc in Maria Eriksson's research group.
The researchers will now continue their work to investigate whether physical exercise can affect the number of accumulated mutations. Is it true that physical exercise from a young age clears out cells with many mutations, or does it result in the generation of a higher number of such cells?
"We aim to discover whether it is possible to individually influence the burden of mutations. Our results may be beneficial for the development of exercise programmes, particularly those designed for an aging population," says Maria Eriksson.:
 https://medicalxpress.com/news/2018-02-stem-cell-result-stronger-muscles.html  

Yale-NUS researchers discover drug cocktail that increases lifespan

23 October 2018
Life-extending effects in worms could one day translate into treatments that delay ageing in humans
A team of researchers led by Principal Investigator Dr Jan Gruber from Yale-NUS College has discovered a combination of pharmaceutical drugs that not only increases healthy lifespan in the microscopic worm Caenorhabditis elegans (C. elegans), but also delays the rate of ageing in them, a finding that could someday mean longer, healthier lives for humans.
The study, published in the peer-reviewed international journal Developmental Cell on 8 October 2018, lays crucial groundwork for further research into designing drug combinations that produce the same effect in mammals.
“Many countries in the world, including Singapore, are facing problems related to ageing populations,” said Dr Gruber, whose lab and research team made the discovery. “If we can find a way to extend healthy lifespan and delay ageing in people, we can counteract the detrimental effects of an ageing population, providing countries not only medical and economic benefits, but also a better quality of life for their people.”
Dr Gruber is an Assistant Professor of Science (Biochemistry) at Yale-NUS College and Assistant Professor at the Department of Biochemistry of the Yong Loo Lin School of Medicine at the National University of Singapore (NUS). The study was carried out by Dr Gruber’s research team in collaboration with researchers from the Singapore Lipidomics Incubator (SLING) at the Life Sciences Institute of NUS.
Dr Gruber’s team wanted to find out to what extent healthy lifespan could be extended by combining drugs targeting several pathways (underlying biological mechanisms) known to affect lifespan. For instance, the drug rapamycin is currently administered following organ transplants to prevent the body’s immune system from rejecting the transplanted organs, but previous experiments by other research groups showed that it extends the lifespan of many organisms, including the C. elegans worms, fruit flies and mice.
Dr Gruber’s team administered combinations of two or three compounds targeting different ageing pathways to C. elegans. Results showed that two drug pairs in particular extended the mean lifespan of the worms more than each of the drugs individually, and in combination with a third compound almost doubled mean lifespans. This effect is larger than any lifespan extension that has previously been reported for any drug intervention in adult animals.
The drug treatments had no adverse effect on the worm’s health. The researchers also discovered that across all ages, the treated worms were healthier and spend a larger percentage of their already extended lifespans in good health.
This is an important point for potential future human ageing interventions as increased health span, not just increased lifespan, would have significant medical and economic benefits. “We would benefit not only from having longer lives, but also spend more of those years free from age-related diseases like arthritis, cardiovascular disease, cancer, or Alzheimer’s disease,” Dr Gruber said. “These diseases currently require very expensive treatments, so the economic benefits of being healthier for longer would be enormous.” He cited a 2017 study that determined that if US citizens’ ageing rate was decreased by 20 percent, the US government would save US$7.1 trillion in public health costs over the next 50 years.
Dr Gruber’s lab also collaborated with Yale-NUS Associate Professor of Science (Life Science) Nicholas Tolwinski, who is also an Associate Professor with the Department of Biological Sciences at the NUS Faculty of Science, and found that a species of fruit flies (Drosophila melanogaster) treated with a similar drug cocktail also experienced significant lifespan extension. That two such evolutionarily-distinct organisms experience similar lifespan extensions suggests that the biological mechanisms that regulate these drug interactions on ageing are ancient, making it more likely that similar interactions between ageing pathways could be targeted in humans.
According to Dr Gruber, this study is a proof-of-principle, showing that pharmacological intervention targeting multiple ageing pathways is a promising strategy to slow ageing and dramatically extend healthy lifespan in adult animals.
The next steps for this research will focus on three large areas. The first will be to extend this approach with the aim of designing interventions even more effective than the ones developed in this study. The second area will involve determining the molecular and biological mechanisms of how the drugs interact to delay ageing and increase lifespan in order to develop computer models to simulate these interactions, allowing researchers to test thousands more combinations through computer modelling. The ultimate goal of this line of research would be to develop drug interventions safe enough slow ageing in humans, a goal that is also pursued by many other research teams around the world.


 ‘Smart stent‘ detects narrowing of arteries

Jun 19, 2018   
For every three individuals who have had a stent implanted to keep clogged arteries open and prevent a heart attack, at least one will experience restenosis—the renewed narrowing of the artery due to plaque buildup or scarring—which can lead to additional complications.
Now, a team led by UBC electrical and computer engineering professor Kenichi Takahata has developed a type of “smart stent” that monitors even subtle changes in the flow of blood through the artery, detecting the narrowing in its earliest stages and making early diagnosis and treatment possible.
“We modified a stent to function as a miniature antenna and added a special micro-sensor that we developed to continuously track blood flow. The data can then be sent wirelessly to an external reader, providing constantly updated information on the artery’s condition,” said Takahata.
The device uses medical-grade stainless steel and looks similar to most commercial stents. Researchers say it’s the first angioplasty-ready smart stent—it can be implanted using current medical procedures without modifications.
Research collaborator Dr. York Hsiang, a UBC professor of surgery and a vascular surgeon at Vancouver General Hospital, noted that monitoring for restenosis is critical in managing heart disease.
“X-rays such as CT or diagnostic angiograms, which are the standard tools for diagnosis, can be impractical or inconvenient for the patient,” said Hsiang. “Putting a smart stent in place of a standard one can enable physicians to monitor their patient’s health more easily and offer treatment, if needed, in a timely manner.”
The device prototype was successfully tested in the lab and in a swine model. Takahata, who holds patents for the technology, says his team is planning to establish industry partnerships to further refine the device, put it through clinical trials and eventually commercialize it.
The research is described in the May issue of Advanced Science and featured on its front cover. Engineering researcher Xing Chen, now a research associate at the Johns Hopkins School of Medicine, and Babak Assadsangabi, a postdoctoral fellow at UBC’s faculty of applied science, also contributed to the study.


 Research suggests that humans could one day regrow limbs


Scientists have identified the specific type of planaria flatworm pluripotent stem cell that is capable of regenerating an entire organism
June 15, 2018
In the June 14, 2018, issue of the journal Cell, researchers at Stowers Institute for Medical Research published a landmark study whose findings have important implications for advancing the study of stem cell biology and regenerative medicine, according to the researchers.*
Over a century ago, scientists traced regenerative powers in a flatworm known as planaria to a special population of planaria adult stem cells called neoblasts (a type of adult pluripotent stem cell — meaning a cell that can transform into any type of cell). Scientists believe these neoblasts hold the secret to regeneration. But until recently, scientists lacked the tools necessary to identify exactly which of the individual types of neoblasts were actually capable of regeneration.
However, with a special technique that combined genomics, single-cell analysis, and imaging, the scientists were able to identify 12 different subgroups of neoblasts. The problem was to find the specific neoblasts that were pluripotent (able to create any kind of cell, instead of becoming specific cells, like muscle or skin). By further analyzing the 12 neoblast markers (genetic signatures), they narrowed it down one specific subgroup, called Nb2.
Planarian flatworm adult stem cells known as neoblasts can be clustered based on their gene expression profiles (left panel). A neoblast subpopulation termed Nb2 expresses the cell membrane protein TSPAN-1 (center panel, a representative Nb2 cell with TSPAN-1 protein shown in green and DNA in blue). Nb2 neoblasts were found to be able to repopulate stem cell-depleted animals (right panel, representative animals at different time points after Nb2 single-cell transplants). (credit: Stowers Institute for Medical Research)
To see if the Nb2 type of neoblast was truly capable of regeneration, they irradiated a group of planaria and then inserted the Nb2 into the planaria. They found the Nb2 subgroup was in fact able to repopulate the planaria.
“We have enriched for a pluripotent stem cell population, which opens the door to a number of experiments that were not possible before,” says senior author Alejandro Sánchez Alvarado, Ph.D. “The fact that the marker we discovered is expressed not only in planarians but also in humans suggests that there are some conserved mechanisms that we can exploit.
“I expect those first principles will be broadly applicable to any organism that ever relied on stem cells to become what they are today. And that essentially is everybody.”
* The work was funded by the Stowers Institute for Medical Research, the Howard Hughes Medical Institute, and the National Institute of General Medical Sciences of the National Institutes of Health.

Genome wide association study of epigenetic aging rates in blood reveals a critical role for TERT

HEBREW SENIORLIFE INSTITUTE FOR AGING RESEARCH
Researchers from several institutions, including, UCLA, Boston University, Stanford University and the Institute for Aging Research at Hebrew SeniorLife, analyzed blood samples from nearly 10,000 people to find that genetic markers in the gene responsible for keeping telomeres (tips of chromosomes) youthfully longer, did not translate into a younger biologic age as measured by changes in proteins coating the DNA. This study was recently published in the journal Nature Communications.
DNA methylation age is a biomarker of chronological age and predicts lifespan, but its underlying molecular mechanisms are unknown. In this genome-wide association study, researchers found gene variants mapping to five loci associated with intrinsic epigenetic age acceleration (IEAA) and gene variants in three loci associated with extrinsic epigenetic age acceleration. Variants in the gene called Telomerase Reverse Transcriptase (TERT) on chromosome 5 that were associated with older IEAA were also associated with longer telomeres indicating a critical role for TERT in regulating the epigenetic clock, in addition to its established role of compensating for cell replication-dependent telomere shortening.
Co-author Douglas P. Kiel, M.D., M.P.H, Director, Musculoskeletal Research Center and Senior Scientist at Hebrew SeniorLife's Institute for Aging Research said, "We calculated the epigenetic aging rate for each person using a previously described epigenetic clock method. Next, we related the epigenetic aging rate to millions of genetic locations (SNPs) across all of the chromosomes. Then we studied the SNPs that had very significant associations with epigenetic aging rates. To our surprise, one of these locations was the TERT locus. The finding is surprising because this was not a study of telomere length. TERT is a subunit of the enzyme telomerase, which is a widely known enzyme because it has been touted as an anti-aging enzyme. It has been called a modern fountain of youth. However, some scientists have pointed out that it is unlikely to become a source of anti-aging therapies. Our study highlights the error in the notion that activation of telomerase (as advocated by some) will cure aging. Instead, our study shows that an anti-aging therapy based on telomerase expression would be accompanied by continued aging."
About Institute for Aging Research
Scientists at the Institute for Aging Research seek to transform the human experience of aging by conducting research that will ensure a life of health, dignity and productivity into advanced age. The Institute carries out rigorous studies that discover the mechanisms of age-related disease and disability; lead to the prevention, treatment and cure of disease; advance the standard of care for older people; and inform public decision-making. The Musculoskeletal Center within IFAR studies conditions affecting bone, muscle, and joint health with aging.
About Hebrew SeniorLife
Hebrew SeniorLife, an affiliate of Harvard Medical School, is a national senior services leader uniquely dedicated to rethinking, researching and redefining the possibilities of aging. Based in Boston, the non-profit, non-sectarian organization has provided communities and health care for seniors, research into aging, and education for geriatric care providers since 1903. For more information about Hebrew SeniorLife, visit http://www.hebrewseniorlife.org, follow us on Twitter @H_SeniorLife, like us on Facebook or read our blog.
https://www.eurekalert.org/pub_releases/2018-02/hsif-gwa020218.php


Loss of mitochondrial SIRT4 shortens lifespan and leads to a decline in physical activity

Sweta Parik, Sandipan Tewary, Champakali Ayyub, Ullas Kolthur-Seetharam
doi: https://doi.org/10.1101/248831
Abstract

Mitochondrial mechanisms and pathways have recently emerged as critical determinants of organismal aging. While nuclear sirtuins have been shown to regulate aging, whether mitochondrial sirtuins do so is still unclear. Here, we report that mitochondrial dSirt4 mediates organismal survival. We establish that absence of dSirt4 leads to reduced lifespan independent of dietary inputs. Further by assaying locomotion, a key correlate of aging, we demonstrate that dSirt4 null flies are severely physically impaired with a significant reduction in locomotion. In summary, we report for the first time that mitochondrial dSirt4 is a key determinant of longevity and its loss leads to early aging. https://www.biorxiv.org/content/early/2018/01/16/248831

Gene Expression-Based Drug Repurposing to Target Ageing
 View ORCID ProfileHandan Melike Donertas, Matias Fuentealba Valenzuela, Linda Partridge, Janet Thornton
https://doi.org/10.1101/253344
Abstract

Ageing is the largest risk factor for a variety of non-communicable diseases. Model organism studies have shown that genetic and chemical perturbations can extend both life- and health-span. Ageing is a complex process, with parallel and interacting mechanisms contributing to its aetiology, posing a challenge for the discovery of new pharmacological candidates to ameliorate its effects. In this study, instead of a target-centric approach, we adopt a systems level drug repurposing methodology to discover drugs that could combat ageing in human brain. Using multiple gene expression datasets from brain tissue, taken from patients of different ages, we first identified the expression changes that characterise ageing. Then, we compared these changes in gene expression with drug perturbed expression profiles in the Connectivity Map. We thus identified 24 drugs with significantly associated changes. Some of these drugs may function as anti-ageing drugs by reversing the detrimental changes that occur during ageing, others by mimicking the cellular defense mechanisms. The drugs that we identified included significant number of already identified pro-longevity drugs, indicating that the method can discover de novo drugs that meliorate ageing. The approach has the advantages that, by using data from human brain ageing data it focuses on processes relevant in human ageing and that it is unbiased, making it possible to discover new targets for ageing studies. https://www.biorxiv.org/content/early/2018/01/24/253344


Mild depolarization of the inner mitochondrial membrane is a crucial component of an anti-aging program

PNAS first published March 9

Significance

The mitochondria, organelles that produce the largest amounts of ATP and reactive oxygen species (mROS) in living cells, are equipped with a universal mechanism that can completely prevent mROS production. This mechanism consists of mild depolarization of the inner mitochondrial membrane to decrease the membrane potential to a level sufficient to form ATP but insufficient to generate mROS. In short-lived mice, aging is accompanied by inactivation of the mild depolarization mechanism, resulting in chronic poisoning of the organism with mROS. However, mild depolarization still functions for many years in long-lived naked mole rats and bats.

Abstract

The mitochondria of various tissues from mice, naked mole rats (NMRs), and bats possess two mechanistically similar systems to prevent the generation of mitochondrial reactive oxygen species (mROS): hexokinases I and II and creatine kinase bound to mitochondrial membranes. Both systems operate in a manner such that one of the kinase substrates (mitochondrial ATP) is electrophoretically transported by the ATP/ADP antiporter to the catalytic site of bound hexokinase or bound creatine kinase without ATP dilution in the cytosol. One of the kinase reaction products, ADP, is transported back to the mitochondrial matrix via the antiporter, again through an electrophoretic process without cytosol dilution. The system in question continuously supports H+-ATP synthase with ADP until glucose or creatine is available. Under these conditions, the membrane potential, ∆ψ, is maintained at a lower than maximal level (i.e., mild depolarization of mitochondria). This ∆ψ decrease is sufficient to completely inhibit mROS generation. In 2.5-y-old mice, mild depolarization disappears in the skeletal muscles, diaphragm, heart, spleen, and brain and partially in the lung and kidney. This age-dependent decrease in the levels of bound kinases is not observed in NMRs and bats for many years. As a result, ROS-mediated protein damage, which is substantial during the aging of short-lived mice, is stabilized at low levels during the aging of long-lived NMRs and bats. It is suggested that this mitochondrial mild depolarization is a crucial component of the mitochondrial anti-aging system…:


Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging
 modified FOXO4-p53 interfering peptide causes p53 nuclear exclusion in senescent cells
·         This FOXO4 peptide induces targeted apoptosis of senescent cells (TASC)
·         TASC neutralizes murine liver chemotoxicity from doxorubicin treatment
·         TASC restores fitness, hair density, and renal function in fast and naturally aged mice
Summary

The accumulation of irreparable cellular damage restricts healthspan after acute stress or natural aging. Senescent cells are thought to impair tissue function, and their genetic clearance can delay features of aging. Identifying how senescent cells avoid apoptosis allows for the prospective design of anti-senescence compounds to address whether homeostasis can also be restored. Here, we identify FOXO4 as a pivot in senescent cell viability. We designed a FOXO4 peptide that perturbs the FOXO4 interaction with p53. In senescent cells, this selectively causes p53 nuclear exclusion and cell-intrinsic apoptosis. Under conditions where it was well tolerated in vivo, this FOXO4 peptide neutralized doxorubicin-induced chemotoxicity. Moreover, it restored fitness, fur density, and renal function in both fast aging XpdTTD/TTD and naturally aged mice. Thus, therapeutic targeting of senescent cells is feasible under conditions where loss of health has already occurred, and in doing so tissue homeostasis can effectively be restored.


Scientists decipher mechanisms in cells for extending human longevity
A sirtuin-dependent intermittent pattern of chromatin silencing during yeast aging that is crucial for longevity

November 6, 2017
A team of scientists at the University of California San Diego led by biologist Nan Hao have combined engineering, computer science, and biology technologies to decode the molecular processes in cells that influence aging.
Protecting DNA from damage
As cells age, damage in their DNA accumulates over time, leading to decay in normal functioning — eventually resulting in death. But a natural biochemical process known as “chromatin silencing” helps protect DNA from damage by converting specific regions of DNA from a loose, open state into a closed one, thus shielding DNA regions. (Chromatinis a complex of macromolecules found in cells, consisting of DNA, protein, and RNA.)
Among the molecules that promote silencing is a family of proteins — broadly conserved from bacteria to humans — known as sirtuins. In recent years, chemical activators of sirtuins have received much attention and are being marketed as nutraceuticals (such as resveratrol and more recently, NMN, as discussed on KurzweilAI) to aid chromatin silencing in the hopes of slowing the aging process.
To silence or not to silence? It’s all about the dynamics.
However, scientists have also found that such chromatin silencing also stops the protected DNA regions from expressing RNAs and proteins that carry out biological functions, so excessive silencing could derail normal cell physiology.
To learn more, the UC San Diego scientists turned to cutting-edge computational and experimental approaches in yeast, as described in an open-access study published in Proceedings of the National Academy of Sciences. That allowed the researchers to track chromatin silencing in unprecedented detail through generations during aging.
Here’s the puzzle: They found that a complete loss of silencing leads to cell aging and death. But continuous chromatin silencing also leads cells to a shortened lifespan, they found. OK, so is chromatin silencing or not silencing the answer to delay aging? The answer derived from the new study: Both.
According to the researchers, nature has developed a clever way to solve this dilemma. “Instead of staying in the silencing or silencing loss state, cells switch their DNA between the open (silencing loss) and closed (silencing) states periodically during aging,” said Hao. “In this way, cells can avoid a prolonged duration in either state, which is detrimental, and maintain a time-based balance important for their function and longevity.”
What about nutraceuticals?
So are nutraceuticals to aid chromatin silencing still advised? According to a statement provided to KurzweilAI, “since the study focused on yeast aging, much more investigation is needed to inform any questions about chromatin silencing and nutraceuticals for human benefit, which is a much more complex issue requiring more intricate studies.”
“When cells grow old, they lose their ability to maintain this periodic switching, resulting in aged phenotypes and eventually death,” explained Hao. “The implication here is that if we can somehow help cells to reinforce switching, especially as they age, we can slow their aging. And this possibility is what we are currently pursuing.
“I believe this collaboration will produce in the near future many new insights that will transform our understanding in the basic biology of aging and will lead to new strategies to promote longevity in humans.”
The research was supported by the National Science Foundation, University of California Cancer Research Coordinating Committee (L.P.); Department of Defense, Air Force Office of Scientific Research, National Defense Science and Engineering; Human Frontier Science Program; and the San Diego Center for Systems Biology National Institutes of Health.

Nan Hao | This time-lapse movie tracks the replicative aging of individual yeast cells throughout their entire life spans.

Nan Hao | periodic switching during aging


Abstract of Multigenerational silencing dynamics control cell aging
Cellular aging plays an important role in many diseases, such as cancers, metabolic syndromes, and neurodegenerative disorders. There has been steady progress in identifying aging-related factors such as reactive oxygen species and genomic instability, yet an emerging challenge is to reconcile the contributions of these factors with the fact that genetically identical cells can age at significantly different rates. Such complexity requires single-cell analyses designed to unravel the interplay of aging dynamics and cell-to-cell variability. Here we use microfluidic technologies to track the replicative aging of single yeast cells and reveal that the temporal patterns of heterochromatin silencing loss regulate cellular life span. We found that cells show sporadic waves of silencing loss in the heterochromatic ribosomal DNA during the early phases of aging, followed by sustained loss of silencing preceding cell death. Isogenic cells have different lengths of the early intermittent silencing phase that largely determine their final life spans. Combining computational modeling and experimental approaches, we found that the intermittent silencing dynamics is important for longevity and is dependent on the conserved Sir2 deacetylase, whereas either sustained silencing or sustained loss of silencing shortens life span. These findings reveal that the temporal patterns of a key molecular process can directly influence cellular aging, and thus could provide guidance for the design of temporally controlled strategies to extend life span.

Walking DNA nanorobot could deliver a drug to a precise location in your body
Future uses could include creating programmable drugs or delivering them when a specific signal is received in the bloodstream or cells
Caltech scientists have developed a “cargo sorting” DNA nanorobot programmed to autonomously “walk” around a surface, pick up certain molecules, and drop them off in designated locations.
The research is described in a paper in the Friday, September 15, 2017 issue of Science.
The major advance in this study is “their methodology for designing simple DNA devices that work in parallel to solve nontrivial tasks,” notes Duke University computer scientist John H. Reif in an article in the same issue of Science.
Such tasks could include synthesizing a drug in a molecular factory or delivering a drug only when a specific signal is present in bloodstreams, say the researchers. “So far, the development of DNA robots has been limited to simple functions,” the researchers note.
Walking nanobots that work in parallel
The DNA nanorobot, intended as a proof of concept, has a “leg” with two “feet” for walking, and an “arm” and “hand” for picking up cargo. It also has a segment that can recognize a specific drop-off point and signal to the hand to release its cargo. Each of these building blocks are made of just a few nucleotides (molecules that form DNA) within a single strand of DNA.*
As the robot encounters cargo molecules tethered to pegs, it grabs them with its “hand” components and carries them around (with a 6-nm step size) until it detects the signal of the drop-off point.
In experiments, the nanorobots successfully sorted six randomly scattered molecules into their correct places in 24 hours. The process is slow, but adding more robots to the surface shortened the time it took to complete the task. The very simple robot design utilizes very little chemical energy, according to the researchers.**
“The same system design can be generalized to work with dozens of types of cargos at any arbitrary initial location on the surface,” says lead author Anupama Thubagere. “One could also have multiple robots performing diverse sorting tasks in parallel,” [programmed] like macroscopic robots.”
Future applications
“We don’t develop DNA robots for any specific applications. Our lab focuses on discovering the engineering principles that enable the development of general-purpose DNA robots,” explains Lulu Qian, assistant professor of bioengineering.
“However, it is my hope that other researchers could use these principles for exciting applications, such as synthesizing a therapeutic chemical from its constituent parts in an artificial molecular factory, or sorting molecular components in trash for recycling. Just like electromechanical robots are sent off to faraway places, like Mars, we would like to send molecular robots to minuscule places where humans can’t go, such as the bloodstream.”
Funding was provided by Caltech Summer Undergraduate Research Fellowships, the National Science Foundation, and the Burroughs Wellcome Fund.
* The key to designing DNA machines is the fact that DNA has unique chemical and physical properties that are known and programmable. A single strand of DNA is made up of four different molecules called nucleotides—abbreviated A, G, C, and T—and arranged in a string called a sequence. These nucleotides bond in specific pairs: A with T, and G with C. When a single strand encounters a “reverse complementary strand” — for example, CGATT meets AATCG —the two strands zip together in the classic double-helix shape.
** Using these chemical and physical principles, researchers can also design “playgrounds,” such as molecular pegboards, to test them on, according to the researchers. In the current work, the DNA robot moves around on a 58-nanometer-by-58-nanometer pegboard on which the pegs are made of single strands of DNA complementary to the robot’s leg and foot. The robot binds to a peg with its leg and one of its feet — the other foot floats freely. When random molecular fluctuations cause this free foot to encounter a nearby peg, it pulls the robot to the new peg and its other foot is freed. This process continues with the robot moving in a random direction at each step.
Abstract of A cargo-sorting DNA robot
Two critical challenges in the design and synthesis of molecular robots are modularity and
algorithm simplicity.We demonstrate three modular building blocks for a DNA robot that
performs cargo sorting at themolecular level. A simple algorithm encoding recognition between
cargos and their destinations allows for a simple robot design: a single-stranded DNA with
one leg and two foot domains for walking, and one arm and one hand domain for picking up and
dropping off cargos.The robot explores a two-dimensional testing ground on the surface of
DNA origami, picks up multiple cargos of two types that are initially at unordered locations, and
delivers them to specified destinations until all molecules are sorted into two distinct piles.
The robot is designed to perform a random walk without any energy supply. Exploiting this
feature, a single robot can repeatedly sort multiple cargos. Localization on DNA origami allows
for distinct cargo-sorting tasks to take place simultaneously in one test tube or for multiple
robots to collectively perform the same task.
references:

Miniature MRI simulator chip could help diagnose and treat diseases in the body at sub-millimeter precision
September 13, 2017
Caltech researchers have developed a “Fantastic Voyage” style prototype microchip that could one day be used in “smart pills” to diagnose and treat diseases when inserted into the human body.
Called ATOMS (addressable transmitters operated as magnetic spins), the microchips could one day monitor a patient’s gastrointestinal tract, blood, or brain, measuring factors that indicate a patient’s health — such as pH, temperature, pressure, and sugar concentrations — with sub-millimeter localization and relay that information to doctors. Or the devices could even be instructed to release drugs at precise locations.
An open access paper describing the new device appears in the September issue of the journal Nature Biomedical Engineering. The lead author is Manuel Monge, who now works at Elon Musk’s new Neuralink company.
Abstract of Localization of Microscale Devices In Vivo using Addressable Transmitters Operated as Magnetic Spins
The function of miniature wireless medical devices, such as capsule endoscopes, biosensors and drug-delivery systems, depends critically on their location inside the body. However, existing electromagnetic, acoustic and imaging-based methods for localizing and communicating with such devices suffer from limitations arising from physical tissue properties or from the performance of the imaging modality. Here, we embody the principles of nuclear magnetic resonance in a silicon integrated-circuit approach for microscale device localization. Analogous to the behaviour of nuclear spins, the engineered miniaturized radio frequency transmitters encode their location in space by shifting their output frequency in proportion to the local magnetic field; applied field gradients thus allow each device to be located precisely from its signal’s frequency. The devices are integrated in circuits smaller than 0.7 mm3 and manufactured through a standard complementary-metal-oxide-semiconductor process, and are capable of sub-millimetre localization in vitro and in vivo. The technology is inherently robust to tissue properties, scalable to multiple devices, and suitable for the development of microscale devices to monitor and treat disease.
references:
These fast, low-cost medical technologies will replace ultrasound and X-rays for specific uses
September 8, 2017
Smartphone instant heart diagnosis (credit: Caltech)
A radical software invention by three Caltech engineers promises to allow your smartphone camera* to provide detailed information about a critical measure of your heart’s health: the “left ventricular ejection fraction” (LVEF) — the amount of blood in the heart that is pumped out to the blood system with each beat. This figure is used by physicians as a base for diagnostic and therapeutic decisions.
You’ll simply hold your phone up to your neck for a minute or two.
In an experiment, the technique was found to be as accurate as a 45-minute echocardiography scan, which currently requires a trained technician operating an expensive ultrasound machine.
The smartphone technique measures how much the carotid artery displaces the skin of the neck as blood pumps through it. In a normal heart, the LVEF measure ranges from 50 to 70 percent. When the heart is weaker, less of the total amount of blood in the heart is pumped out with each beat, and the LVEF value is lower.
Carotid arterial waveform captured using an unmodified iPhone 5S camera by placing the iPhone camera over the carotid pulse (credit: Niema M. Pahlevan et al./Critical Card Medicine)
To test the app, clinical trials were conducted with 72 volunteers between the ages of 20 and 92 at an outpatient magnetic resonance imaging (MRI) facility. MRI is the gold standard in measuring LVEF but is seldom used clinically due to its high cost and limited availability. The measurements made by smartphone had a margin of error of ±19.1 percent compared with those done in an MRI. By way of comparison, the margin of error for echocardiography is around ±20.0 percent.
 “This has the potential to revolutionize how doctors and patients can screen for and monitor heart disease, both in the U.S. and the developing world,” says Caltech’s Mory Gharib, the Hans W. Liepmann Professor of Aeronautics and Bioinspired Engineering and senior author of a paper on the study in the July issue of the Journal of Critical Care Medicine.
The researchers have founded a start-up named Avicena, LLC that has licensed this technology and will market the app. They also plan to use this approach to diagnose heart-valve diseases, like aortic stenosis and coronary artery blockage.
* For the study, the team used an iPhone 5, but they say any smartphone with a camera will work.
Seeing through the body
University of Edinburgh and Heriot-Watt University researchers have used a near-infrared camera to see through the chest to track the location of a fiber-optic endomicroscope (a long flexible tube with a light on the end) — replacing X-rays.
A “time-of-flight” camera detects light emitted from an endoscope in sheep lungs. Left: light emitted from the tip of the endoscope, revealing its precise location in the lungs. Right: an image using a conventional camera, with light scattered through the structures of the lung. (credit: Proteus)
Near-infrared light can readily pass through the body, but much of it scatters or bounces off tissues and organs rather than traveling straight through — making it nearly impossible to get a clear picture of where an object is in the body. So this camera uses a “time-of-flight” system: It calculates the distance to the endomicroscope light based on the time it takes individual photons to arrive directly (ignoring scattered photons, which take longer). That’s similar to how this camera can see an object around a corner.
The technology is so sensitive it can detect the miniscule amount of light that passes through 20 centimeters (about 8 inches) of the body’s tissue.
The research is described in an open-access paper in the journal Biomedical Optics Express.
Abstract of Noninvasive iPhone Measurement of Left Ventricular Ejection Fraction Using Intrinsic Frequency Methodology
Objective: The study is based on previously reported mathematical analysis of arterial waveform that extracts hidden oscillations in the waveform that we called intrinsic frequencies. The goal of this clinical study was to compare the accuracy of left ventricular ejection fraction derived from intrinsic frequencies noninvasively versus left ventricular ejection fraction obtained with cardiac MRI, the most accurate method for left ventricular ejection fraction measurement.
Design: After informed consent, in one visit, subjects underwent cardiac MRI examination and noninvasive capture of a carotid waveform using an iPhone camera (The waveform is captured using a custom app that constructs the waveform from skin displacement images during the cardiac cycle.). The waveform was analyzed using intrinsic frequency algorithm.
Setting: Outpatient MRI facility.
Subjects: Adults able to undergo MRI were referred by local physicians or self-referred in response to local advertisement and included patients with heart failure with reduced ejection fraction diagnosed by a cardiologist.
Interventions: Standard cardiac MRI sequences were used, with periodic breath holding for image stabilization. To minimize motion artifact, the iPhone camera was held in a cradle over the carotid artery during iPhone measurements.
Measurements and Main Results: Regardless of neck morphology, carotid waveforms were captured in all subjects, within seconds to minutes. Seventy-two patients were studied, ranging in age from 20 to 92 years old. The main endpoint of analysis was left ventricular ejection fraction; overall, the correlation between ejection fraction–iPhone and ejection fraction–MRI was 0.74 (r = 0.74; p < 0.0001; ejection fraction–MRI = 0.93 × [ejection fraction–iPhone] + 1.9).
Conclusions: Analysis of carotid waveforms using intrinsic frequency methods can be used to document left ventricular ejection fraction with accuracy comparable with that of MRI. The measurements require no training to perform or interpret, no calibration, and can be repeated at the bedside to generate almost continuous analysis of left ventricular ejection fraction without arterial cannulation.
Abstract of Ballistic and snake photon imaging for locating optical endomicroscopy fibres
We demonstrate determination of the location of the distal-end of a fibre-optic device deep in tissue through the imaging of ballistic and snake photons using a time resolved single-photon detector array. The fibre was imaged with centimetre resolution, within clinically relevant settings and models. This technique can overcome the limitations imposed by tissue scattering in optically determining the in vivo location of fibre-optic medical instruments.
references:
Niema M. Pahlevan; Derek G. Rinderknecht; Peyman Tavallali; Marianne Razavi; Thao T. Tran; Michael W. Fong; Robert A. Kloner; Marie Csete; Morteza Gharib. Noninvasive iPhone Measurement of Left Ventricular Ejection Fraction Using Intrinsic Frequency Methodology. Critical Care Medicine. 45(7):1115–1120, JUL 2017; DOI: 10.1097/CCM.0000000000002459
M. G. Tanner, T. R. Choudhary, T. H. Craven, B. Mills, M. Bradley, R. K. Henderson, K. Dhaliwal, and R. R. Thomson, "Ballistic and snake photon imaging for locating optical endomicroscopy fibres," Biomed. Opt. Express 8, 4077-4095 (2017); DOI: 10.1364/BOE.8.004077 (open access)

Intercellular competition and the inevitability of multicellular aging
1.     Paul Nelsona,1 and Joanna Masela

Significance
We lay out the first general model of the interplay between intercellular competition, aging, and cancer. Our model shows that aging is a fundamental feature of multicellular life. Current understanding of the evolution of aging holds that aging is due to the weakness of selection to remove alleles that increase mortality only late in life. Our model, while fully compatible with current theory, makes a stronger statement: Multicellular organisms would age even if selection were perfect. These results inform how we think about the evolution of aging and the role of intercellular competition in senescence and cancer.
Abstract

Current theories attribute aging to a failure of selection, due to either pleiotropic constraints or declining strength of selection after the onset of reproduction. These theories implicitly leave open the possibility that if senescence-causing alleles could be identified, or if antagonistic pleiotropy could be broken, the effects of aging might be ameliorated or delayed indefinitely. These theories are built on models of selection between multicellular organisms, but a full understanding of aging also requires examining the role of somatic selection within an organism. Selection between somatic cells (i.e., intercellular competition) can delay aging by purging nonfunctioning cells. However, the fitness of a multicellular organism depends not just on how functional its individual cells are but also on how well cells work together. While intercellular competition weeds out nonfunctional cells, it may also select for cells that do not cooperate. Thus, intercellular competition creates an inescapable double bind that makes aging inevitable in multicellular organisms.: http://www.pnas.org/content/early/2017/10/25/1618854114

Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets

Summary
Here, we present a large (n = 107,207) genome-wide association study (GWAS) of general cognitive ability (“g”), further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with general cognitive ability. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis implicated the biological processes of neurogenesis and synaptic regulation, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker, and LY97241, a potassium channel inhibitor. Transcriptome-wide and epigenome-wide analysis revealed that the implicated loci were enriched for genes expressed across all brain regions (most strongly in the cerebellum). Enrichment was exclusive to genes expressed in neurons but not oligodendrocytes or astrocytes. Finally, we report genetic correlations between cognitive ability and disparate phenotypes including psychiatric disorders, several autoimmune disorders, longevity, and maternal age at first birth.: http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31648-0

Does Religion Stave Off the Grave? Religious Affiliation in One’s Obituary and Longevity

Abstract
Self-reported religious service attendance has been linked with longevity. However, previous work has largely relied on self-report data and volunteer samples. Here, mention of a religious affiliation in obituaries was analyzed as an alternative measure of religiosity. In two samples (N = 505 from Des Moines, IA, and N = 1,096 from 42 U.S. cities), the religiously affiliated lived 9.45 and 5.64 years longer, respectively, than the nonreligiously affiliated. Additionally, social integration and volunteerism partially mediated the religion–longevity relation. In Study 2, exploratory analyses suggested that the religion–longevity association was moderated by city-level religiosity and city-level personality. In cities with low levels of trait openness, the nonreligiously affiliated had reduced longevity in highly religious cities relative to less religious cities, consistent with the religion-as-social-value hypothesis. Conversely, in cities with high levels of openness, the opposite trend was observed, suggesting a spillover effect of religion. The religiously affiliated were less influenced by these cultural factors.

http://journals.sagepub.com/doi/full/10.1177/1948550618779820

Phenotypic Age: a novel signature of mortality and morbidity risk
July 5, 2018.

doi: https://doi.org/10.1101/363291


How to predict the side effects of millions of drug combinations
Doctors have no idea, but Stanford University computer scientists have figured it out, using artificial intelligence

July 11, 2018

An example graph of polypharmacy side effects derived from genomic and patient population data, protein–protein interactions, drug–protein targets, and drug–drug interactions encoded by 964 different polypharmacy side effects. The graph representation is used to develop Decagon. (credit: Marinka Zitnik et al./Bioinformatics) Ref.: Bioinformatics (open access). Source: Stanford University.


Research shows it's possible to reverse damage caused by aging cells

August 15, 2018, University of Minnesota
What's the secret to aging well? University of Minnesota Medical School researchers have answered it- on a cellular level.
Aging starts in our cells, and those aging cells can hasten cellular senescence, leading to tissue dysfunction and related health impacts.
New research involving University of Minnesota Medical School faculty Paul D. Robbins and Laura J. Niedernhofer, recently published in Nature Medicine, shows there are types of small molecules called senolytics that can reverse the impact of aged, senescent cells.
"We've always thought of aging as a process, not a disease," said Dr. Robbins, Associate Director of the newly founded Institute on the Biology of Aging and Metabolism (iBAM). "But what if we can influence the impacts of aging at a cellular levelto promote healthy aging? That's what senolytics seeks to achieve."
The research determined whether introducing senescent cells to human and animal tissue would impact the cellular health of surrounding cells. Surprisingly, the transplant of a relatively small number of senescent cells caused persistent physical dysfunction as well as the spread of cellular senescence in previously healthy cells.
In addition, researchers found that a high fat diet, which causes a type of metabolic stress, or simply being old, enhances the physical dysfunction that comes from senescent cells.
"Previous research has shown that our immune system's ability to eliminate or deal with senescent cells is based 30 percent on genetics and 70 percent on environment," said Dr. Robbins, noting that what we eat and how often we exercise can affect senescence or aging of cells.
Conversely, the researchers determined that treatment with senolytic drugs, able to eliminate senescent cells, can reverse physical dysfunction and actually extend lifespan even when used in aged animal models.
"We saw greater activity, more endurance, and greater strength following use of senolytics," said Dr. Robbins.
The paper notes that the results provide proof-of-concept evidence that improved health and lifespan in animals is possible by targeting senescent cells. The hope is that senolytics will prove effective in alleviating physical dysfunction and resulting loss of independence in older adult humans as well.
"This area of research is promising, not just to address the physical decline that comes with aging, but also to enhance the health of cancer survivors treated with radiation or chemotherapy—two treatments that can induce cell senescence," said Laura Niedernhofer, Director of iBAM.
More information: Ming Xu et al, Senolytics improve physical function and increase lifespan in old age, Nature Medicine(2018). DOI: 10.1038/s41591-018-0092-9 


Coalition for radical life extension

Our Purpose
is to unite a critical mass of like-minded people who support radical life extension and physical immortality in order to inspire revolutionary change in how radical life extension is viewed in our world.
But we need you.
Make a tax deductible donation
The Coalition for Radical Life Extension is a Not-for-Profit 501 (C)(3), EIN: 84-0581094: http://www.rlecoalition.com/

Human Longevity Inc

Take Control of Your Health with Health Nucleus
Stay ahead of aging and illness

United Therapeutics

United Therapeutics Corporation focuses on the strength of a balanced, value-creating biotechnology model. We are confident in our future thanks to our fundamental attributes, namely our obsession with quality and innovation, the power of our brands, our entrepreneurial culture and our bioinformatics leadership. We also believe that our determination to be responsible citizens – having a positive impact on patients, the environment and society – will sustain our success in the long term.
Through our wholly-owned subsidiary, Lung Biotechnology PBC, we are focused on addressing the acute national shortage of transplantable lungs and other organs with a variety of technologies that either delay the need for such organs or expand the supply. Lung Biotechnology is the first public benefit corporation subsidiary of a public biotechnology or pharmaceutical company.

Calico google's human longevity project

Our culture is shaped by our values—they are a framework that sets expectations and guides employees’ behavior.
Our values inform the big and small decisions we make every day: the science and business decisions, and also how we decide to collaborate with our colleagues within and outside the company. We may succeed. We may fail. But, by working together, with integrity and respect, we will always be doing things the right way, and we just might achieve something that others may not believe possible.
We use the following core values to guide us on our journey:
  • INNOVATION: We believe tackling aging and increasing healthspan can only succeed with cutting-edge science and transformative technology and that both are fueled by intellectual freedom and creativity
  • INTEGRITY: We expect everyone to be honest, ethical and trustworthy
  • COURAGE: We aim high, make tough decisions and take smart risks
  • ACCOUNTABILITY: We value taking personal responsibility and look inward first when things do not go well
  • COLLABORATION: We understand that working together can expand possibilities and capabilities
  • GENEROSITY OF SPIRIT: We strive to be kind and considerate, respect each other’s individuality and perspectives and graciously share both ideas and credit


We are builders. We create tools that put health data into action.
Verily lives at the intersection of technology, data science and healthcare. Our mission is to make the world's health data useful so that people enjoy healthier lives.
Verily is developing tools to collect and organize health data, then creating interventions and platforms that put insights derived from that health data to use for more holistic care management. We have three guiding product design principles: start with the user, simplify care, and lead on security and privacy.


The technologies that could transform ageing

By Frank Swain 5th November 2020

Providing a growing older generation with a dignified and independent life means doing more with less – and governments and industry are looking to cutting-edge technology to help.

https://www.bbc.com/future/article/20201104-the-technologies-that-could-transform-ageing

‘The Longevity Code: Secrets to Living Well for Longer from the Front Lines of Science’

by Kris Verburgh 

We all know that we age—but do you know exactly how, and why? And do you wonder what you can do-whatever your age-to slow the process so you can live well, for longer? This book comprehensively answers these questions. Medical doctor and polymath scientist Kris Verburgh illuminates the biological mechanisms that make our bodies susceptible to heart attacks, strokes, dementia, diabetes, and other aging-related diseases. We learn about the crucial role of poorly functioning mitochondria, shortened telomeres, proteins and carbohydrates, and more. Having explained the aging process at work, Dr. Verburgh then provides the tools we need to slow it down: his scientifically backed Longevity Staircase. This simple yet innovative step-by-step method offers better health and a longer life span through nutrition-currently our best defense in the fight against aging and disease. And with each passing day, advances in biotechnology-once the stuff of science fiction-are emerging as part of the "longevity code". Dr. Verburgh discusses how new types of vaccines, mitochondrial DNA, CRISPR proteins, and stem cells may help us slow and even reverse aging-now and in the future.

https://www.goodreads.com/book/show/51482371-the-longevity-code

Death, Physics and Wishful Thinking

Fear of mortality might underlie physicists’ fondness for the anthropic principle, multiverses, superdeterminism and other shaky ideas

Terror-management theory can account for puzzling political trends, such as our attraction to outlandish conspiracies and authoritarian leaders. Last year I invoked the theory to explain why Donald Trump’s popularity surged at the beginning of the COVID-19 pandemic. Recently I have begun to wonder whether terror-management theory can explain trends in physics, too….: https://www.scientificamerican.com/article/death-physics-and-wishful-thinking

TRANSCEND 9 steps to living well forever.
publication year: 2010
In 2004, Ray Kurzweil and Terry Grossman, MD, published Fantastic Voyage: Live Long Enough to Live Forever. Their groundbreaking book marshaled thousands of scientific studies to make the case that new developments in medicine and technology will allow us to radically extend our life expectancies and slow down the aging process. Soon, our notion of what it means to be a 55-year-old will be as outdated as an eight-track tape player.
TRANSCEND: Nine Steps to Living Well Forever presents a practical, enjoyable program so that readers can live long enough (and remain healthy long enough) to take full advantage of the biotech and nanotech advances that have already begun and will be occurring at an accelerating pace during the years ahead. To help readers remember the nine key components of the program, Ray and Terry have arranged them into a mnemonic:  Talk with your doctor Relaxation Assessment Nutrition Supplementation Calorie reduction Exercise New technologies Detoxification  This easy-to-follow program will help readers transcend the boundaries of our genetic legacy and live long enough to live forever.


Chasing immortality | The Future is Now

https://www.youtube.com/watch?v=P5GntKFGjtE

 

IMMORTALITY: How close is it?

https://www.youtube.com/watch?v=d85q7s3Q1E4





                 
   


26.04.2017.

1 komentārs:

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