Work on Senolytic Rejuvenation Therapies Begins to Attract More Mainstream Notice
This popular science piece on the development of senolytic therapies capable of clearing harmful senescent cells from aging tissues is a cut above the average. It is important to see more publicity for this line of work. Not because it will aid the industry, but because the more attention that is given to the field, the faster that existing senolytic treatments such as the dasatinib and quercetin combination will become available through off-label prescription and physician networks. Tens of millions of patients with inflammatory age-related diseases caused in part by senescent cells, and the many cancer survivors with high burdens of senescent cells due to chemotherapy, and diabetics whose condition is mediated by senescent cells, and the obese whose visceral fat tissue spurs cellular senescence might benefit in the US alone, if they only knew that senolytics exist today.
The choice on whether to try now or wait for more human data for dasatinib and quercetin (or fisetin, or piperlongumine, or other easily obtained senolytics) should be one that people are permitted to make, not one they remain ignorant of because nobody bothered to tell them that it exists. My one complaint about the content of this article is that the author does conspicuously fail to mention that it is possible to obtain access to the first senolytic treatments today, at very low cost, and that older people in the self-experimentation community are indeed choosing to do this.
Imagine if instead of a pill you could take to live for ever there was a pill that could push back the ageing process - a medicine that could stave off the frailty, osteoarthritis, memory loss, macular degeneration, and cancers that plague old age. It could happen, with the science of senolytics: an emerging - and highly anticipated - area of anti-ageing medicine. Many of the world's top gerontologists have already demonstrated the possibilities in animals and are now beginning human clinical trials, with promising results. If the studies continue to be as successful as hoped, those who are currently middle-aged could become the first generation of oldies who are youthful for longer - with a little medical help.
Researchers are at work on senolytics, a branch of medicine that targets senescent cells; the various faulty cells that have been identified as instrumental in our eventual demise. These so-called "zombie" cells linger and proliferate as we age, emitting substances that cause inflammation and turn other healthy cells senescent, ultimately leading to tissue damage throughout the body. In 2011 a team showed that "using a genetic trick to get rid of these senescent cells can significantly improve health and lifespan" in prematurely aged mice. In 2016, the same group achieved similar results in naturally aged mice, releasing an arresting image of two elderly rodents born of the same litter. The one cleared of its senolytic cells seems spry and glossy, while its sibling is shrunken, greying and looks its age.
A new company, called Unity Biotechnology, was formed to raise funds to develop medicine that could safely clear zombie cells from the human body. Trials in senolytics are initially targeting specific conditions such as age-related macular degeneration, glaucoma, and chronic obstructive pulmonary disease (which includes emphysema). Most are in the fledgling stages, working on rodents or human tissue in petri dishes, although in February a small early human trial showed an improvement in the distance patients were able to walk. Also this year, a pre-clinical pilot trial for injecting a senolytic drug into the knees of people with osteoarthritis showed promising, if mixed results. It is hoped that, eventually, there will be a number of senolytic drugs that could potentially target different senescent cell types, but currently much of the research has involved a combination of a leukaemia drug called dasatinib and quercetin, a polyphenol common in plants.
Senolytics are particularly exciting because "they seem to still work very late in life. So it will be possible to study more quickly whether they actually work in humans, and they are applicable to people already at the end of their lives." In theory at least, it should prove impossible to build up a resistance to the drugs, "because senescent cells cannot proliferate". Even more importantly, there is significant data to show "that you don't have to treat these patients every single day. You just treat them once a week or once a month. Intermittent treatment is more than enough to have huge benefits." These aren't the only potential added benefits. Senescent cells "play a big role after cancer treatment", developing as a result of chemotherapy and radiation therapy. "If senolytics can be used to help eliminate the damaged cells before they can spread, a detrimental side-effect of cancer treatment could be alleviated."
this will not happen again, last chance. biolife4d have now opened their crowd investing campaign again:
https://biolife4d.com
And headlines are as retarded as ever.
Puff piece as Unity waits for the moment of truth in next clinical trial
Stock down over 65%
Ridiculous short selling going on - https://finance.yahoo.com/quote/UBX/key-statistics?p=UBX
Admin, do you think those senolytics and other anti-aging therapies might become prescription drugs ? I mean why would a doctor prescribe a drug if you have no illness ? Unless aging is considered a disease by the FDA, but that's a long shot.
For example the senolytic for knee arthritis will be prescribed for people with arthritis, not for "healthy" people in their 40s or more.
@Jonathan Weaver:
They ARE and always will be prescription drugs. If you can prove they reduce the risk of a particular chronic disease for anyone above age X with biomarkers in certain ranges, they'll get prescribed to people in that age range. That's already done with statins and throxine.
@Dylan Mah
So there's no way we can rejuvenate legally to our 20-25 years old state then ?
@Jonathan Weaver
Of course. There will be doctors who are willing to prescribe senolytics for off-label use. But don't expect that costs will be covered by insurance from the get-go.
I wonder - if it is a newly developed drug or therapy, how long it's going to take for the European FDA to approve the drug. If its up to a year I might take my parents up to a trip to the US.
The title of the article is so hyperbolic it has persuaded me not to read the article.
"Even more importantly, there is significant data to show "that you don't have to treat these patients every single day. You just treat them once a week or once a month."
Is this correct? Until now I had the impression it is more like every couple of years.
@Chris: No-one knows what the optimal dose schedule is, but I would be surprised to see it turn out to be as often as even once every three months. Yearly doesn't sound unreasonable based on the pace of creation of these cells.
@Jonathan Weaver: We don't see senescent cells starting to build up in tissue until you're in your 40s or 50s. That age is when you start seeing chronic disease risks skyrocketing. Ultimately Getting people to a health state similar to the 20s is going to be extraordinarily difficult and would likely require therapies beyond anything currently conceived of; keeping the risk of age related diseases from rising past what we see in middle age is potentially doable, and there's very good reason to think we can attenuate the rate at which that risk increases and delay the onset of old age based on studies in multiple animal models.
@Reason: One peculiar thing I've noticed in Unity's data is that there seems to be a time lag after treatment before results become apparent. After 3 months, NSF was highly significant, WOMAC-A was just short of statistically significant, and WOMAC-C showed a clinically significant correlation, but that wasn't present in their second phase I study when they took measurements after 5 weeks.
The tests of Dasatanib + Quercitin in IPF also showed no statistically significant change from the control after 3 weeks in functional terms, but if there's a delayed response to senolysis a longer term study might reveal genuine efficacy for senolytics against IPF.
Actually Reason, those who've undergone chemo have a greater burden of DNA damaged cells - they're not necessarily senescent until they try and undergo division. This is why post chemo patients that put on weight become frail - the forced division of damaged mesenchymal stem cells to produce new adipocytes causes senescence. But yes, they would benefit from senolytics!
@Dylan Mah
You litterally shattered my dream of being 20 years old again. I'm not really interested in being a 30 or 35 years old, that's still too old for my taste. Rejuvenation have no point if you cannot go back to your early 20s...
Hi Jonathan! Just a 2 cents.
Dylan is quite right about this, getting back to 20 is one hell of a feat. The more 'general effect' could be about going back to your 30s...40s even...not 20s. Of course, We Wish that...but that is immense rejuvenation reversal. Going back to 20 for a 60-70 year old is, truly, a feat. Remember that there is a huge 'gulf' between 20 and 50s...some 50 year old 'keep a rejuvenated' appearance and could pass for 25-30 (mostly women, certain women of 50 look ultra-young, about 20, like a teenager 'biologically' basically but in older adult body...but, most, don't, and look about their chronological age, 40-50 or so, even higher than 50 for the fast agers). Studies that compared 20 year old vs 50-60 years old show that in those next 30-40 years...there is substantial loss and accumulation of damage (it is error to say 'damages start at 50'...they started long before that, even in 'whole life-healthy' people. I.e. there is Clear difference both epigenetically and in terms of damages between a person who is 20 (both bio and chronologically) and someone 60 (both bio and chronologically)). With taht said, as specified, certain people - are 50-60 chronologically...but not biologically (like say 35-40 (epi)biologically); hence, they look almost half their chronological 'years' age. A 20 body is Very Young...and that will be Very Hard to get back to; but, I'm confident we can make it; epigenetic reversal is the first step towards that for it allows to erase the aging signature (on the clock); and that's crucial, also reversing telomere loss, because we will Never/impossible go back to 20 if our telomeres continue shrinking/there is no change to them. The only 'possible' is that we would need an infinite intake of stem cells - which could rebuild all our tissues; don't count on it because studies with 'stem cells' have been very inconclusive in mouse and not some holy grail that reverses mice to young self; they still die on clock, stem cell injection or not.This means we must absolutely be able to make stem cells that cover All Cells/all tissues and can rebuild the body from top to toe; entirety; otherwise, stem cells will remain therapeutical/slow disease progression as the stem cell will differentiatie themselves to rebuild failing organs/cells. Hydras/Jellyfish (turritopsis nutricula) are *mmortal - because they reverse aging via 'asexual' reproduction and 'growth reversal' 'rejuvenation/youthning' epiprogram, they need primordial germ stem cells for their eternal lifespan; when their stem cells are blocked or when the - telomerase - in their stemm cells are blocked; they die like regular/become mortal; demonstrating, that stem cell can offer eternal lifespan; but so far, it only works, in 'simple' organisms (like jellyfish worm, not complex high-order mammals with many organs/'errors waiting to happen'; one doctor said: ''The cost of high complexity (in 'error-prone/mutation-prone' humans/bodies/mammals) is mortality...while very simple 'error-free' organisms (bacterias/jellyfishworm), obtain the *mmortality'')).
Just a 2 cents.
@Jonathan Weaver: When it comes to looking young externally that may be achievable, and there's always cosmetics. I think good health is far more important.
Honestly I would choose to live only 30 years with the look of a 20 years old rather than to live 200 years while looking 40 or 50. Everyone have differents priorities.
@Jonathan Weaver
now we are on the brink of being able to slow it down not really reverse . But once you can reverse it from 90 to 60, then why not from 60 to 40. From this point on, once proved and well funded, eventually 100 to 20 will be doable. And it might be easier to go from 30 to 20 then from 60 to 50. After all, there is less accumulated changes and damage.
@cuberat
" reversing the negative effects of aging will ultimately be far more feasible to implement than "slowing down" the rate at which damage occurs" Aubrey de Grey
It's quite the opposite of what you said.
Re
The way I see it, in order to reach 200 years lifespan, you must revert to a very young body and telomere elongation - is Unconditional, for that lifespan to happen. Meaning it has to be one of two things, or (preferably) both : telomere elongation and/or reduction of telomere attrition speed/rate. A very recent new study showed that indeed; telomeres/rate of shortening = epigenetic aging = telomeres/rate of shortening. And, it makes sense, both telomeres and epigenome are on chromosome; both are part of it, they talk to each other. Chromosomes need methylation/methylome to work/be silenced, just like telomeres and genes do. Tall telomeres are highly methylated and have high telomerase activity. Tall telomeres mean many cell cycles ahead and stable genome (tall telomeres do increase possibility of mutations because high telomerase) but, the negative of it is Less than having Short telomeres (meaning high telomeres = immunity = cancer killing power; inversely, short telomeres/fast telomere shortening = immunosenescence = cancer). Jellyfish are eternal and you can bet they keep tall telomeres in their stem cells; why they are eternal. Tall telomeres means protection of important proteins and DNA strands, histones, chromosomes, it also means less lipofuscin/lysosomal mass, more 'tidy' autophagy/mitophagy and healthy mitos (OXPHOS ETC) with low mtROS emission, and areduced redox milieu. It was even demonstrated that progerin (prelamin-a) accumulation is slowed when telomere attrition is slowed too. So is p53, p21, p16, Caspases, TNF-a, no Beta-Galactosidase staining, no flattening/widening of cells and stop the whole inflammatory circus. Plus, they saw reduced 'clumping' and 'aggregation' of 'proteins' (that form clump - tau, amyloid, plaques, fibrosis, etc). But, especially, chaperones (HSP/HSF/HEME-Oxygenase) and thiol/sulfur proteins (redox/NRF2/ARE/EPRE) which maintain homeostasis/autophagy functioning. Tall telomeres also mean higher SIR/DAF in nucleus, which they slow down cell growth and are crucial for longevity (Calorie restriction rely on SIR/DAF/FOXO/IGF/mTOR/autophagy)
Studies on naked mole rats showed that they have neglible senescence - they barely lose any telomeres with age (albatros have 'increase' of telomeres with age, they still die, but that's not because of telomeric biological reasons). It's simple no therapy can reverse aging if it does not affect the epiclock or telomeric DNA somehow; because these are the 'core clocks' (including the Circadian Clock (For sleep...one study showed that the Circadian Clock is actually directly related to telomeres...thus, sleep patterns, dramatically affect telomeres; because of the circadian clock; during your sleep, the body does 'telomerase boost' (by circadian clock activating 'night genes') and thus, there is telomeric consolidation during your sleep)). But, the bigger one above that 'sleep clock', is the epiclock (it's the one the keeps tabs 'time calendar' on cells).There is thus communication between the telomeric clock, the epiclock and the circadian clock; could be even other ones.
Just a 2 cents.
@Jonathan Weaver
Ultimately yes, but in the next 3 to 4 decades we will be slowing it with some partial reversal here and there.
Well done to the journalist Amy Fleming, I think this is the first mainstream journalistic piece that doesn't raise the usual knee jerk objections to keeping people healthier longer and alive longer such as overpopulation, only for the rich etc.
Hopefully this was a result of her being able to quickly find and read more informed coverage on places like fightaging! before composing her piece.
@Jonathan Weaver, you must be very young if all you think about is looks. Health is so much more important.
Jonathan, enjoy your 20's but what you'll find out is that as you grow older attraction tastes change. Most, not all, 40 year olds are attracted to people that look their own age. Few 40 year old women are attracted to 20 year old looking men, and believe it or not most 40 year old men are not into 20 year old women. Nature matures our tastes along with everything else as we age. What seems inconceivable at 22 - feeling sexy at 50 - actually comes to pass...That said, a healthy fit 50 year old is always going to be more attractive to their peers than someone who has let themselves go.