Longum
iter est per praecepta, breve et efficax per example
Vecuma
pārvarēšana
Mūsdienu civilizācijas sasniegumi ļauj
prognozēt, ka jau pašreiz ekonomiski attīstītajās valstīs dzīvojošajai vidējai
paaudzei tiks nodrošināti apstākļi būtiskai vidējās dzīves ilguma
palielināšanai (apmēram simt gadu robežās). Vienlaikus tiks radītas tādas
iespējas, kas ļaus veikt novecojušā organisma atjaunošanu. Veidojoties bioloģiskai un
kibernētiskai simbiozei, tiek ielikti pamati cilvēka personības nemirstībai.
Šeit sniegtas dažas publikācijas, lai
palīdzētu ieskatīties šajā prognozējamajā nākotnē.
Jāuzsver, ka šādi cilvēces progresa rezultāti var kļūt arī par reālu
apdraudējumu uz humānisma principiem organizētai sabiedriskajai iekārtai. Tas
var īstenoties:
1) ja
nemirstību iegūst valstu vadītāji – diktatori, kuri nevilcināsies izplatīt totalitārismu un pasludināt savas varas
pilnvaras par mūžīgām, bet autokrātiju - par labāko tautas pārvaldes
formu;
2) ja
mākslīgais saprāts kļūs par dominējošo spēku vēl pirms tā ētiskās
humanizācijas.
Lai šādus civilizācijas attīstības riskus novērstu, vitāli nepieciešams
pakāpeniski, soli pa solim reformēt demokrātiju par patiesu tautvaldību,
novēršot tās līdzšinējo manipulatīvo raksturu un veicinot gudra elektorāta
izaugsmi (sk. rakstu “Par reālpolitikas attīrīšanās
iespējām” https://ceihners.blogspot.com).
Ervins Ceihners
17.04.2017.
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
Zinātnieki atklājuši uzturvielu, kas
palēnina novecošanu
"Ko Ārsti Tev Nestāsta"
Neviens nevēlas novecot un ciest no
hroniskiem veselības traucējumiem. Pēc dažu zinātnieku domām, ja tiks gūts
apstiprinājums kādas uzturvielas spēcīgajai iedarbībai, šis process vairs nebūs
neizbēgams.
Pētnieki atklājuši, ka alfa
liposkābe novērš sekas, ko rada hroniskas slimības kā ateroskleroze,
kas nelabvēlīgi iespaido artērijas, un cukura diabēts.
Tas notiek tāpēc, ka
organisms tiek stimulēts pastiprināti izdalīt telomerāzes enzīmu, un tas
veicina telomēru (hromosomu beigu daļu) augšanu. Saīsināti telomēri liecina par
organisma novecošanu un vienlaikus paātrina šo procesu.
Alfa liposkābe
ir antioksidants, kuru izstrādā mūsu organisms, lai glikozi pārvērstu enerģijā.
To var uzņemt arī ar sarkano gaļu un alus raugu vai uztura bagātinātājiem (kas
ir laba ziņa cilvēkiem, kuri neēd gaļu).
Zinātnieki no Emorija
universitātes Medicīnas skolas gan atzīst, ka pagaidām minēto teoriju pamato
pētījumi, kas veikti tikai ar pelēm. Patiesībā zinātnieki nav pārliecināti, ka
cilvēki varētu panākt tādu pašu rezultātu alfa liposkābes noturīguma un
bioloģiskās pieejamības dēļ
http://jauns.lv/raksts/vesels/266846-zinatnieki-atklajusi-uzturvielu-kas-palenina-novecosanu
02.03.2019 00:04
Jaunas zāles labākai un garākai
dzīvei
Valters Bolēvics, Starptautisko
inovatīvo farmaceitisko firmu asociācija
Ar unikālu gēnu terapiju
atjaunot redzi, likt organismam uzsākt cīņu ar agresīvām vēža šūnām vai novērst
smagu invaliditāti, tā ļaujot dzīvot daudz ilgāk, bez sāpēm un ciešanām, – šie
un daudzi citi farmācijas nozares sasniegumi pēdējos gados no zinātniskās
fantastikas kļuvuši par taustāmu realitāti.
Latvijā pārstāvētie
starptautiskie zāļu ražotāji, kas apvienojušies Starptautisko inovatīvo
farmaceitisko firmu asociācijā (SIFFA), piedāvā iepazīties ar pēdējo gadu
spilgtākajiem atklājumiem, kā arī skaidro jauno zāļu ietekmi uz mūža ilgumu....
Unikāla gēnu terapija redzes atjaunošanai...
Būtisks jaunums multiplās sklerozes
slimniekiem...
Programmē šūnas, kas nogalina vēzi...:
Izmantotie avoti:
https://www.efpia.eu/media/25055/the-pharmaceutical-industry-in-figures-june-2016.pdf
https://www.novartis.com/news/media-releases/novartis-announces-landmark-eu-approval-one-time-gene-therapy-luxturna-restore-vision-people-rare-inherited-retinal-disease
https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/car-t-cell1.html
Kalifornijas
universitātes pētnieku eksperimentā gluži nejauši veikts unikāls atklājums –
pazemināts dalībnieku bioloģiskais vecums.
Par to raksta žurnāls "Nature".
Zinātnieku mērķis nemaz nebija mūžīgā jaunība, viņi tikai plānoja pārbaudīt, kā
uz imūnsistēmu iedarbojas trīs diezgan plaši lietoti medikamenti, tos patērējot
vienlaikus. Pēc gada atklājās, ka zāļu kokteilim ir blakne – visi brīvprātīgie bija kļuvuši vidēji par divarpus gadiem
jaunāki.
“Es biju gatavs redzēt [bioloģiskā] pulksteņa palēnināšanos, bet ne
atpakaļgaitu,” "Nature" citē ģenētikas profesoru, pētījuma
līdzautoru Stīvu Horvatu. “Tas izskatījās diezgan futūriski.”
Bioloģisko vecumu nosaka noteikti DNS marķieri, kas mainās novecošanas gaitā.
Tie rāda organisma funkcionālo stāvokli un var gan apsteigt kalendāro vecumu,
gan atpalikt no tā.
Novecošanas biomarķierus atklāja pirms pusgadsimta,
un kopš tā laika daudzi zinātnieki meklē iespējas pagarināt jaunību.
Stenforda Medicīnas centrā veiktajam eksperimentam sākotnēji bija cits uzdevums.
Imunologs Gregorijs Fahi no Losandželosas vēlējās noskaidrot, cik droši ir izmantot
augšanas hormona (somatotropīna) injekcijas, lai atjaunotu audus
aizkrūtes dziedzerī jeb tīmusā. Šim nelielajam orgānam ir svarīga loma
imūnsistēmā, bet ar laiku tas sarūk izmēros un aizaug ar taukaudiem.
Pētījumos ar dzīvniekiem atklāts, ka augšanas
hormons palīdz aizkrūtes dziedzera atjaunošanā, tomēr vienlaikus veicina cukura
diabētu. Tāpēc kopā ar somatotropīna injekcijām brīvprātīgie saņēma
divus plaši zināmus pretdiabēta preparātus – prasteronu un metformīnu.
Pētījuma autori gan atzīst, ka eksperimenta mērogs
bijis pārāk mazs un bez kontrolgrupas salīdzināšanai. Piedalījās tikai deviņi
cilvēki, visi baltie vīrieši vecumā no 51 līdz 65 gadiem. Gada laikā viņiem
regulāri ņēma asins analīzes un eksperimenta sākumā un beigās veica magnētiskās
rezonanses tomogrāfiju.
Septiņiem dalībniekiem bija novērota dziedzera reģenerācija, un visiem
uzlabojās asins rādītāji. Pēc tam imunologam Fahi ienāca prātā parādīt
rezultātus profesoram Horvatam, kurš ir izstrādājis vienu no precīzākajām
bioloģiskā vecuma mērīšanas metodēm. Viņš atklāja, ka dalībnieku bioloģiskais
vecums atpaliek no reālā, turklāt sešiem asins analīzes par to liecināja vēl
pusgadu pēc eksperimenta beigām – terapijas efekts bija ilgstošs. Tagad
zinātnieki gatavojas veikt daudz plašāku pētījumu tieši šajā virzienā.
Pētījumos noskaidrots, ka ticība Dievam
spēj ietekmēt fizisko veselību
Ja jums patīk
piedalīties derībās, kurās īsti nemaz nevar zaudēt, vai drīkstu jūs
iepazīstināt ar “Paskāla derībām”? Arguments, ko formulēja franču matemātiķis
un filozofs Blēzs Paskāls, skan aptuveni šādi: Dievs vai nu eksistē, vai ne,
mēs to nevaram uzzināt. Taču varam izvēlēties – ticēt Dievam vai ne. Ja
ticēsim, dzīvosim laimīgāku dzīvi. Ja Dievs eksistē, mēs nokļūsim debesīs; ja
Dievs neeksistē, mēs tāpat būsim nodzīvojuši laimīgāku mūžu.
Ateisti
ir kritizējuši Paskāla pieņēmumu, ka, tikai ticot Dievam, mēs dzīvosim
laimīgāk, tomēr kāds jauns pētījums apliecina, ka Paskālam bija taisnība. Cilvēki, kas tic Dievam vai augstākam spēkam, ir laimīgāki,
turklāt viņi ir veselīgāki.
Lielbritānijas
Nacionālais statistikas birojs ir izpētījis, ka cilvēki ar reliģisku pārliecību
biežāk nekā ateisti bija apmierinātāki ar savu veselību un retāk smēķēja.
Komentējot
pētījuma rezultātus, Londonas ekumeniskā centra Coexist House
programmu vadītājs Maikls Veiklins teica: “Tas ir saistīts ar attieksmi pret pateicību. Ja ticat domai, ka Dievs jūs
mīl un viņš jūs ir radījis, jums ir lielāka iespēja būt pateicīgiem par to, kas
jums ir. Tāpat, ja esat ticīgi, jūs biežāk nekā ateisti cerēsiet uz labāku
nākotni un ticēsiet – lai arī tagad dzīve nav viegla, ar laiku viss
uzlabosies.”
Bet
svarīga ir ne tikai pateicība. Citi pētnieki, kas analizējuši saistību starp
ticību un labsajūtu, ir ievērojuši arī divus citus faktorus: kopīguma un piederības izjūtu un nojautu, ka eksistē kaut kas augstāks par mums.
Vienā
pētījumā Kentas Universitātes zinātnieki secināja, ka ticība ir
tas, kas nodrošina “pozitīvu novecošanu” jeb gara, veselīga un jēgpilna mūža nodzīvošanu.
Reliģiska
ticība dod
dzīvei veidolu un jēgu, turklāt grūtos brīžos nodrošina sociālo atbalstu un
kopienu.
Djūka
Universitātes psihiatrs Harolds Kēnigs ir veltījis savu karjeru reliģijas
un garīguma ietekmes pētniecībai, lai noskaidrotu, kādu iespaidu tā atstāj uz
mūsu garīgo un fizisko veselību. Viņš atsaucas uz Djūka Universitātes
pētījumiem, kas liecina, kā reliģiska ticība palīdz uzveikt depresiju
un ka ticīgi slimnieku kopēji paši nodzīvo garāku mūžu.
Beidzamajā
pētījumā Kēnigs secināja, ka piederība reliģijai
palēnina novecošanas procesu. Šis fenomens ir novērojams fiziski,
jo pagarinās telomēru dzīves ilgums. Telomēri ir veidojumi hromosomu
galos, un tie ir saistīti ar novecošanu.
Telomēru
noturību visskaidrāk varēja novērot dalībniekiem ar visstiprāko ticību.
“Ticība sniedz mums jēgu, un, kad
kalpojam, mēs to darām ar nojausmu par augstāku spēku,” stāsta Kristīna
Pučalski no Džordža Vašingtona garīguma un veselības institūta.
Sapratne par šo kopīgo saikni mums ļauj būt iecietīgiem pret citu ciešanām,
jeb, kā teicis psihiatrs Viktors Frankls, cilvēku nesagrauj ciešanas. Viņu
sagrauj bezjēdzīgas ciešanas.
Savos
pētījumos Pučalski ievēroja, ka ticīgi cilvēki dzīvoja ilgāk, turklāt viņiem
bija zemāks interleikīna-6 līmenis. Šis proteīns ir hronisku slimību
bioloģiskais marķieris. Reliģiozi cilvēki arī bija garīgi noturīgāki
slimībās, sāpēs un stresā. Un, kā atklāja Hārvarda Universitātes kardiologs
Herberts Bensons un citi, kas pētījušo ticības ietekmi uz mūsu veselību, ticīgi
cilvēki ātrāk atlaba no slimībām un operācijām.
Tomēr
ir arī sliktas ziņas. Reliģiska ticība var veicināt garīgo veselību un palīdzēt
cilvēkiem grūtībās, īpaši tad, ja viņiem ir grupas vai draudzes atbalsts, taču
šādai ticībai var būt arī negatīva ietekme. Priekšstats par elli vai grēku var
bojāt cilvēka garīgo labsajūtu, tāpat kā ticība debesīm un piedošanai var
šķietami uzlabot psihisko pašsajūtu.
Iespējams,
psihologs vai psihiatrs, kam ar pacientu ir kopīga ticība, varētu sniegt labu
padomu un akcentēt reliģijas labvēlīgos aspektus. Nelaime tā, ka šādu
speciālistu nav daudz. Kādā pētījumā atklāts, ka, jautāti par svarīgiem
faktoriem viņu dzīvē, pacienti reliģiju minēja divreiz biežāk nekā
psihiatri. Varbūt psihiatri nebija dzirdējuši par Paskāla derībām.
https://jauns.lv/raksts/par-veselibu/438564-petijumos-noskaidrots-ka-ticiba-dievam-spej-ietekmet-fizisko-veselibu
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.
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
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
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.
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)
IMAGE: DISCOVERING THE KEY TO REVEALING THE SECRET OF REVERSIBLE AGING
RECOVERY. view more
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 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:
·
Jun Li, Michael S. Bonkowski, Sébastien Moniot, Dapeng
Zhang, Basil P. Hubbard, Alvin J. Y. Ling, Luis A. Rajman, Bo Qin, Zhenkun Lou,
Vera Gorbunova, L. Aravind, Clemens Steegborn, David A. Sinclair. A conserved
NAD binding pocket that regulates protein-protein interactions during aging.
Science, 24 Mar 2017: Vol. 355, Issue 6331, pp. 1312-1317 DOI:
10.1126/science.aad8242
Topics: Biomed/Longevity | Biotech
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.
How to program DNA like we do computers
Researchers program DNA molecules to follow specific
instructions to create sophisticated molecular machines for medical and
research uses
December 18, 2017
A programmable chemical
oscillator made from DNA (credit: Ella Maru Studio and Cody Geary)
Researchers at The
University of Texas at Austin have programmed DNA molecules to follow specific
instructions to create sophisticated molecular machines that could be capable
of communication, signal processing, problem-solving, decision-making, and
control of motion in living cells — the kind of computation previously only
possible with electronic circuits.
Future applications may
include health care, advanced materials, and nanotechnology.
As a demonstration, the
researchers constructed a first-of-its-kind chemical oscillator that uses only
DNA components — no proteins, enzymes or other cellular components — to create
a classic chemical reaction network (CRN) called a “rock-paper-scissors
oscillator.” The goal was to show that DNA alone is capable of precise, complex
behavior.
A systematic pipeline for
programming DNA-only dynamical systems and the implementation of a chemical
oscillator (credit: Niranjan Srinivas et al./Science)
Chemical oscillators have
long been studied by engineers and scientists. For example, the researchers who
discovered the chemical oscillator that controls the human circadian rhythm —
responsible for our bodies’ day and night rhythm — earned the 2017 Nobel Prize
in physiology or medicine.
“As engineers, we are very
good at building sophisticated electronics, but biology uses complex chemical
reactions inside cells to do many of the same kinds of things, like making
decisions,” said David Soloveichik, an assistant professor in the Cockrell
School’s Department of Electrical and Computer Engineering and senior author of
a paper in the journal Science.
“Eventually, we want to be
able to interact with the chemical circuits of a cell, or fix malfunctioning
circuits or even reprogram them for greater control. But in the near term, our
DNA circuits could be used to program the behavior of cell-free chemical
systems that synthesize complex molecules, diagnose complex chemical
signatures, and respond to their environments.”
The team’s research was
conducted as part of the National Science Foundation’s (NSF) Molecular
Programming Project and funded by the NSF, the Office of Naval Research, the
National Institutes of Health, and the Gordon and Betty Moore Foundation.
Programming a Chemical
Oscillator
Abstract of Enzyme-free
nucleic acid dynamical systems
An important goal of
synthetic biology is to create biochemical control systems with the desired
characteristics from scratch. Srinivas et al. describe the creation of a
biochemical oscillator that requires no enzymes or evolved components, but
rather is implemented through DNA molecules designed to function in strand
displacement cascades. Furthermore, they created a compiler that could
translate a formal chemical reaction network into the necessary DNA sequences that
could function together to provide a specified dynamic behavior.
references:
Niranjan Srinivas, James Parkin, Georg Seelig, Erik Winfree, David
Soloveichik. Enzyme-free nucleic acid dynamical systems. Science 15 Dec 2017:
Vol. 358, Issue 6369, eaal2052; DOI: 10.1126/science.aal2052
Ultrasound-powered nanorobots clear
bacteria and toxins from blood
The U.S. Defense
Threat Reduction Agency aims to create a broad-spectrum detoxification robotic
platform
June 5, 2018
Engineers at the University
of California San Diego have developed tiny ultrasound-powered nanorobots that
can swim through blood, removing harmful bacteria and the toxins they produce.
These proof-of-concept
nanorobots could one day offer a safe and efficient way to detoxify and
decontaminate biological threat agents — providing an fast alternative to
the multiple, broad-spectrum antibiotics currently used to treat
life-threatening pathogens like MRSA
bacteria (an antibiotic-resistant staph strain). MRSA is considered a
serious worldwide threat to public health.
Antimicrobial resistance
(AMR) threatens the effective prevention and treatment of an ever-increasing
range of infections caused by bacteria, parasites, viruses and fungi, according to the World Health Organization — an
increasingly serious threat to global public health.
Trapping pathogens
The researchers coated gold
nanowires with a hybrid of red blood cell membranes and platelets (tiny blood
cells that help your body form clots to stop bleeding).*
- The platelets cloak the nanowires and attract
bacterial pathogens, which become bound to the nanorobots.
- The red blood cells then absorb and neutralize
the toxins produced by these bacteria.
The interior gold nanowire
body of the nanorobots responds to ultrasound, causing the nanorobots to swim
around rapidly (no chemical fuel required) — mimicking the movement of natural
motile cells (such as red blood cells). This mobility helps the nanorobots
efficiently mix with their targets (bacteria and toxins) in blood and speed up
detoxification.
The coating also protects
the nanorobots from a process known as biofouling — when proteins collect onto
the surface of foreign objects and prevent them from operating normally.
The nanorobots are just over
one micrometer** (1,000 nanometers) long (for comparison, red blood cells have
a diameter of 6 to 8 micrometers). The nanorobots can travel up to 35
micrometers per second in blood when powered by ultrasound.
In tests, the researchers
used the nanorobots to treat blood samples contaminated with MRSA and their
toxins. After five minutes, these blood samples had three times less
bacteria and toxins than untreated samples.
Broad-spectrum detoxification
Future work includes tests
in mice, making nanorobots out of biodegradable materials instead of gold, and
tests of also using the nanorobots for drug delivery.
The ultimate research goal
is not to use the nanorobots specifically for treating MRSA infections, but
more generally for detoxifying biological fluids — “an important step toward
the creation of a broad-spectrum detoxification robotic platform,” as the researchers
note in a paper.
* The researchers
created the nanorobots in three steps:
1. They created
the hybrid coating by first separating entire membranes from platelets and red
blood cells.
2. They applied
ultrasound (high-frequency sound waves) to fuse the membranes together. (Since
the membranes were taken from actual cells, they contain all their
original-cell surface protein functions, including the ability of platelets to
attract bacteria.)
3. They coated
these hybrid membranes onto gold nanowires.
** A micrometer
is one millionth of a meter, or one thousandth of a millimeter.
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