George Church on Reprogramming as a Treatment for Aging
In a recent interview, George Church offers opinions on partial reprogramming as an approach to rejuvenation. In the last few years this has moved from popular topic to becoming a sizable fraction of the longevity industry, given the large-scale funding that is now devoted to partial reprogramming groups. Short-term exposure to the Yamanaka factors can be used to reset the epigenetic patterns of a cell in old tissue to be more like those of a cell in young tissue, with corresponding gains in function. There are potentially serious issues to be worked out, such as how to eliminate the possibility of cancer due to the few cells that might fully reprogram into pluripotency in a short time, but this is nonetheless an exciting area of medical science that is now heavily funded. We should expect to see significant progress in the years ahead.
Do we understand how cellular reprogramming improves health and longevity?
There have been two major camps in aging since long ago. One says that aging happens due to damage, to proteins, lipids, RNA, and DNA, and that you have to go in there with your repair kit and fix it as a therapist. The other camp says that it's all epigenetic, and that if you convince the cell that it's young, it will get its own toolkit out and start repairing as much as it can. Some things are beyond repair. If you delete all copies of a tumor suppressor, that's not something a young cell can repair. But most things are fixable with epigenetics - at least, that's how the second hypothesis goes.
I believe in a hybrid model. I think most of the work can be done epigenetically. A surprising amount of it can be done via the bloodstream, but probably not all of it. Then, there's a residual amount that you can fix with the Yamanaka factors and another residual amount that you can fix by restoring genes. Since we do the epigenetic reprogramming by adding in genes, it's not that fundamental a difference between adding in genes that will go into the blood, adding genes that will reprogram the nucleus, and adding genes that are missing, like tumor suppressors. In a certain sense, they are all addressable by multiplex gene therapy. That's why being able to either use multiple rounds of dosing or to have bigger vectors will become increasingly important.
Given the rising popularity of partial reprogramming, what is its overall place in the longevity landscape?
I think there are subtle but important differences between anti-aging drugs and drugs that improve biomarkers in the way that statins improve cholesterol. That doesn't mean such drugs increase longevity, just that they improve this one biochemical. It could actually hurt you; for instance, it could improve cardiovascular chances for some subset of the population, but for another subset, it could hasten muscle pain. So, affecting biomarkers is one thing. Reversing diseases of aging is different. You could do it just by addressing that particular disease, or you could do it more broadly, affecting multiple diseases. You might get FDA approval for one of them, but it's actually affecting multiple ones, and maybe acting preventatively. Say, there might be a cure for muscle wasting that helps prevent a variety of diseases. Finally, you're really at the core of aging when you reprogram shared elements - with good feedback systems that already exist in the body or with feedback systems that you introduce as part of the therapy.
Are you bullish about longevity biotech?
I think the whole field is very healthy economically and scientifically. We have passed through multiple "valleys of death". We're now in the solid science phase, and this field is going to be very impactful, maybe more impactful than any other pharmaceuticals in history, including even antibiotics, because our very ability to fight off diseases is age-related. Almost every single form of human morbidity and mortality has an age-related component to it. If you want to have a pleiotropic effect on many different diseases, this is the way to go.
Link: https://www.lifespan.io/news/prof-george-church-on-cellular-reprogramming-and-longevity/
Checking in to take people's temperature on this subject, which I like to do from time to time as a layperson doing his best to parse the available info. It seems like this area is particularly promising and may be among the first to produce dramatic results. There's new and exciting news every couple of months. Overall, how are people feeling? Are we optimistic? How many years are we talking before there are real treatments available in the clinic to reverse aspects of aging? Will senolytics be first, or reprogramming? Which will have a more visible and substantial impact? I live in hope.
"How many years are we talking before there are real treatments available in the clinic to reverse aspects of aging?"
Likely many years before treatment(s) get approval for use in humans in the United States by the FDA. However you would probably be able to travel abroad much sooner to get said treatment; basically a so called "medical vacation/tourism" to receive the treatment in a foreign country.
I'm not optimistic at all and don't think these tratments will be for me - early 60s.
"I'm not optimistic at all and don't think these tratments will be for me - early 60s"
I am approximately the same age as you 63. My/our best bet would be Greg Fahy's Thymus regeneration therapy using Metformin, DHEA, HGH all relatively cheap and available. And the trial TRIIM study was done with people not rats/mice. First trial only had 9 subjects but the currently ongoing follow-up TRIIM-X trial has about 40-50 people
These responses aren't especially optimistic. Mcmp, you don't think senolytics or epigenetic reprogramming will be available in your lifetime? I would have anticipated we were looking at inside ten years for the former, unless we get unlucky.
I think Harold Katcher's young plasma fraction is the most promising. I think it will be tested in humans faster than you think.
@Tim, are you doing all of those things? Have you noticed any improvement? I don't have any background in science, biology or chemistry so, unless they come up with some pill or other easy treatment, I'm ph&cked!
@Ben, naaaa... I've been hearing these claims for decades now and nothing happened. I don't think it will be any different this time.
"@Tim, are you doing all of those things? Have you noticed any improvement? I don't have any background in science, biology or chemistry so, unless they come up with some pill or other easy treatment, I'm ph&cked!"
Myself personally no. Here is some info on Greg Fahy's experiments:
https://www.youtube.com/watch?v=Wqb9c5MRUAs&t=791s
"The Thymus As A Key Target For Aging Intervention - Dr. Greg Fahy - EARD 2022"
He (Fahy) is talking about measurable age reversal by DNA methylation clocks of approx 1.5 yrs per year of treatment. It is still in the experimental stage but unlike Harold Katcher's work it is being done on people not mice (though I understand he is currently running tests on dogs). Although I would agree that it will likely be a race between Fahy and Katcher as to who has treatments generally available to people like us first.
I doubt that it will take less than 30 years. Yamanaka factors were discovered in 2006, then it was 10 years before demonstrating that they could partially reprogram progeroid mice in 2016, and then it took 7 more years until Rejuvenate Bio showed extension of remaining lifespan in regular old mice, a result that needs to be replicated by other labs.
Add to this the fact that before trying to reprogram humans you want to make sure that by doing so you don't give them cancer, it will take at least 15 years before you have systemically rejuvenated larger animals to see if they get sick. Assuming that everything goes well - which it won't at the first try - that's another 10-15 years before the end of human trials.
Maybe a combination of thymus regeneration, plus senolytics, plus a cancer cure, plus degradation of atherosclerotic plaques plus something else will get many of today's 60 year olds to 90 in decent shape, at which point there should be epigenetic reprogramming and who knows what other tricks to reverse aging.
Personally, I am in my mid 40s and I am much less optimistic about my prospects than I was when I first became interested in the field almost 20 years ago. It's not that there hasn't been any progress or a seismic change of attitude as much as I have realised how long it really takes before something that works in a petri dish is made to work in humans.
After reading these pessimistic comments I am sadly concluding that most of us reading this blog are doomed to die.
We can try to slow AGEing and reduce suffering, and making dying painless.
"After reading these pessimistic comments I am sadly concluding that most of us reading this blog are doomed to die."
Well Dr Greg Fahy is in his 70's ( 72 I think but he looks younger) and he is on his protocol as well as Steven Horvath. Of course they have the advantage of being able to treat themselves. Also there is David Sinclair and his NMN/Resveratrol approach (less optimistic about that frankly). Between them and Katchers' work there is a "fighting chance" that people in their `60's might live long enough for stem cell therapies and/or epigenetic re-programming to be perfected. Likely you would have to take a "medical vacation/tourism" and pay for it out of pocket.
At least one person over 60 is thinking positively…
AI could/will change everything in short order
https://www.iflscience.com/futurist-predicts-humans-will-achieve-immortality-by-2030-67965
@Nicholas D, "We can try to slow AGEing and reduce suffering, and making dying painless" - and how do you do that? Have been hearing of some really painful undignified deaths lately and it scares the shit out of me. If you're talking of euthanasia, I don't think I'll ever have the balls to go trough with it, unless I'm in such great pain, I'd rather be dead.
Yea, many pessimistic people here, unfortunately.
I'm a bit over 60 but have hope for LEV.
1. Huge amount of money being put into longevity research. Big increase in last 5 years including Mellon's organization and Altos. Additionally, longevity is becoming more mainstream news.
2. AI should greatly speed up the process.
3. For us older people, it may make sense to use the comprehensive check up that several employees ( Ray K partner Dr. Terry Grossman) and Peter Diamondis offer which I assume also provides latest supplements and/ treatments. I believe their services are pricey, though.
4. And, yes, I'm saving my money ( well, investing) for that inevitably medical tourism. I'm assuming cost of 10 to 100K, but pure guess.
5. Finally, Ray K does have a point of exponential knowledge ( including computer and biological) which most of us can't really imagine.
Great post Robert. And thanks also august33, I read that article myself a few days ago. I'm a big fan of Peter Diamandis and he keeps reinforcing the fact that mindset is so important, especially for success and longevity. Yet so many on here are quick to fall into what I see as unfounded nihilism. AI is gonna change everything so quickly. The world we have now will be unrecognisable come 2030.
For what's worth I'm in my late 40's but can still pass the army PT test for 20 year olds, my blood pressure averages around 110/70 and I frequently get comments that I look much younger. In addition to the general health advice found in David Kekich's book I've been taking Mayo Clinic's fisetin senolytic protocol every three months, did the dasatinib + quercetin 5 day protocol 50 mg/day once and take NOVOS daily faithfully.
I feel highly optimistic that this will buy me enough time for everything Robert posted about LEV.
@Robert, I'm with you and around the same age. My bet is on gene therapy which seems promising to have significant & visible effects as exercise clearly do.
@Barbara T. you probably right with regards to the official FDA like channels. But I'm hoping for medical tourism to speed that up for at least a decade. Fingers crossed.
@ Joe, my bet is firstly on Senolytics treatments and secondly on Partial programming. TBH, not sure how much impact Partial programming will be but glad there are huge amount of funds being put into this besides the sentient cell research.
I understand other areas of anti ageing research are concurrently going on.
BTW, Ray K. believes we'll hit LEV by 2030. AdG is quoting it at about 2037. The exponential increase in knowledge between the 7 years is huge.
I am also assuming about a decade between FDA approval and medical approval.
I think we really like the idea of epigenetic reprogramming because it looks like a silver bullet. Thing is, it probably isn't (there are issues that it can't fix) and either way it will take decades before we find out whether it can produce serious, systemic rejuvenation in humans and whether it doesn't (or does) cause cancer.
I don't know how many people are willing to risk the latter with medical tourism. And even then, these businesses don't publish follow ups so we still won't know until a proper clinical trial tells us.
I think that we will much sooner see results, if more modest and incremental, from things like senolytics and rapamycin. But of course, even in this case it will take many years to find out how much life extension, exactly, you can get with a combination of interventions. It has been proved that sometimes less is more, so I don't think that throwing the kitchen sink at aging will necessarily yield the best results.
This doesn't mean that many 60 year olds won't live to see 100, but thinking that come 2050 we'll magically wake up in a teenage body is a pipe dream.
Hey there! Just a 2 cents. TL DR: It's a long message. We are not being 'nihilists...for being nihilists'...it's really the accumulation of 'being let down/and hoping hoping hoping...' some thing. Yes, some things do happen, some good things...but it oftenly, is very lackluster and just very underwhelming. People can us ''picky/difficult to please'', ''expecting the moon/immortality SoonTM''; but, it's only normal to hope that INDEED aging is defeated..just like this website is called : Fightaging.org....it should be renamed to ''FightawfulresultsAndLowballing-aimingOfHealhtyAgingMisnomerWhoAreYouKiddingButYourOwnSelfLULLedandGetALife.org''.
(/S)
Yes, obviously, nihilism (happening) is understandable; staying positive and optimistic is important/required; but when you 'are at it' for years and years...you can 'run out of steam/gas'
(burn out) and then you lose hope; ''You - Can't!!! (lose hope)''; (--never), if you do......you die.
Hope = live.
Lose hope = die.
Well...
It is not that people want to declare forfeit/give in, and abandon...it's that sometimes, that's exactly what happens; people abandonning things over a very long time and (very thence/late) realizing, that it will not go 'as planned'.
That it is not a 'happy ending' like in movies. (at least, American films....(some) European films, have 'sad endings'...translation: real(er) endings...; it's why people may like not watching them; prefer a nice happy ending ---- ''....and they were forever happy.'' ).
I mean, when I read/saw that AdG abandoned or let's say removed himself from his OWN SENSE thing...it's like..oh boy, I guess his predictions were a 'bit off' and now he realizes, that indeed, it might not happen as he planned; yes, he did say, it was 50/50 chance...but Trust is lost over time when so much hope/trust..is put in this. It's like we have to go blind in this 'and hope for the best'. which is 'asking a lot' for a lot of people...they don't like to 'put hopes and trust...in UN-tangibles and semi-truth/wild theories/outlandish possibilities''.
And, it's true...there is Nothing Else...we can...but hope...or despair and lose hope. So, instead of losing hope, we should - not. Then again, try doing that...over Decades...time passes and fades things....even your Resolve and your Confidence.
Doubt always comes back/seeps in/creeps in, again; years later. It's always there'...just in the background, as you try to keep it 'at bay. Like 'demons' in the closet; 'skeletons in the closet'.
Demons (of old/laying/sleeping), can resurface.
It is great that (older) people are more receptive and want to be optimistic about this; -Obviously, when you are older, time is running out, so ''it's now or never''; not all old people though...some are very nihilistic about it (me, more now) or not nihilistic...but you could be more? realist...about it. As some said....''it's been decades...and not much has changed...and it takes like 15-20 years for 'anything to happen''....I don't - have - 20 years...to wait''. Tangibility of things is what matters, 'concrete/tangible' results...that translate to some therapy or supplement or something..
Time is becoming a luxury, that we cannot afford anymore (to lose, because we running out of it).
Well, mostly, for people that are oldest and in their later mid-to-late life, as seniors; mostly, the baby boomers. Like some others, I am younger (very early 40s), and thus am Gen X (or late genx-old millenial hybrid'..) and like, I know that, though having more time being younger...means not much; sure, you know the saying going: 'live your life, that's all that matters'....but, anti-aging/ biorejuvenation..is about doing this Now...not later...starting 'early' like an early bird. And it's why, these scientists like AdG, Sinclair, Horvath and Mr. Church, are doing regimens (their own ones that tehy discovered), right now, to slow their own aging. And why, they will (possibly) live longer; preserving their bodies younger...longer.
The clock is ticking and we not getting any younger. ''you will be old...before you get any young(er)''. As for researchers that say that we can reverse epiclock by 1 year - each year of time passed....this, we are not there yet. I, sincerely, hope we do. That is tantamount to LEV.
But, getting to that '1 year rejuvenation - per 1 year of time advancement'...is Giant Leap (of faith).
But, alos, people need to temper their expectations (not being nihilist or pessimist) with a dose of realism (and less wishful thinking); as others stated...it just is LONG to 'market' the therapy or whatever (bureacratic red tape and secondary effects/unforeseen problems about a therapy needing to be fixed 'as safe'); and thus, the whole 'medical tourism' as solution in the mean time.
LEV -- seems -- possible, but from I gathered lately,, it still a bit of 'stretch/farfetched'...
not to say we could never make Eternal life/immortalty...we could; but, 'when' is the question..
the Quadrillion $ question. I predict that it will take roughly 50 yaers for anything Remotely close to LEV; we will be able to reach 120 with the technology/progress in the next 50 years ; but LEV, no way, nearly 100% certain.
Why would we not make LEV sooner -- like in 20-30 years time -- exclusind bureacratic red tape?
Mostly, because, of difficulty to make it work in humans, and the whole 'ethical' aspect to it; some people will refuse to do it or be 'guinea pig' for it...I read some comment on youtube about immortality and the person said: ''We are about to witness the highest number of premature deaths in human history''.
Basically, saying that with us trying to make LEV...means will have big consequence and huge sacrifice --> many will die...for LEV to happen.
I want to think that it will never happen that way, and that no one will die...but, if we look at COVID/Vaccine....as real example; then, I guess, ..then, that people will die.
It is nearly impossible to make it 100% reliable and that unforeseen problems (''secondary effects'') would never happen. Meaning, some may die, in the process, of LEV, 'tried' on them.
We know that epigenetic reprogramming, if longer than the reprogramming window - causes - teratoma formation/cancer/tumors to form in mice....and not just that, reprogramming Erases the signature/you lose the signature and the cell de-differentiates back to like a 'stem cell'...and that was tried in mouse, and they died; so you can't make Full Reprogramming it kills the animal because loses its 'signatuer/phenotype' of its cells...and that does not work with organs/animals. You can only PARTIALLY reverse epigenetic/epiclock. Think of it like a 'slate', a 'clean slate' is erased...and that is not possible (Full Reprogramming); you only clean-it...a bit. Not entirely.
We have to keep 'some signature' of ourselves...it's like trying to erase Neurons/content in your brain...we can'T do that.. if we do, we Erase the Person, their Existence; they exist no more and wake up 'not knowing they are' and having No Memory anymore of all they learned throughout their life...and makes them --- Them/TheirSelf/Person(a) (and nobody else). Their soul (it is said 'soul is in the cells', if you believe that).
Being older, you 'have no choice'...time (is) out (soon) and death approaches ('of aging/too old').
Now, it would be a 'roll of the dice' and 'taking your chances'...; because, if you knew the danger (just like taking the vaccine or having COVID), you would be careful Before taking any therapy that purports to reversing aging and obtain LEV. Because, if it did not work, and people died; doubt would creep n seep in your mind and you Doubt of taking it/the risk/chances (on your life).
(''Don't be scared...take it...we all took it.''. One man on the road biking..during COVID, asked me (I was wearing the covid mask) while biking -- ''Are you scared...?''. I could not answer him, that yes, I am/was scared and why I was wearing it, because I am scared of dying; people can have no fear of dying; and 'just accept it...why be afraid...right?...we all die, anyway'...because -- Fear keeps Alive...it is a mechanism to 'make you wake up and 'act' on a danger'; it saves your life; from a danger; by fearing, you do soemthing about it --> protect your life (against would-be danger). Because, sometimes, it is Really a danger (to your life); but beign 'fearful' in life..gets you nowhere; as the saying goes : ''no one went far in life...by being 'scared' all the time''. which is kind of true; we take Risks..and live with it (or die of it). Thus, you have to be fearful - 'Enough only...not TOO fearful, just enough and knowing 'you can' fear...you can Still fear. Because, fear is Highly Highly Stressful on the body and ages you fast. So you can't be in fear continously. It's a Negative Protective Mechanism, meant to get you out of danger/protect your life and used 'sporadically' (cortisol explosion/stress anxiety -> burn candles by both ends). If I had not Feared for my Life, I would be dead, as I suffer(ed) of atherosclerosis/pulmonary embolis, blood clot thrombus...and had I not done anything; I would not be here telling you about it; and this is why, I fear death, because I experienced it/was on my death bed ---- i nearly died, and fear it happening much sooner.). 80%+ die of my disease/atherosclerosis, silent killer that 'accumulates' in your over decades and then, one day, you die from it --- or your survive it (in younger age), like I did.
So, it is normal to doubt and even fear, (and we are not tring to do 'fear mongering').
Just like it happened during COVID. With 'freedom convoy' (in Canada, up here; some people called them 'freedumb clownvoy' or 'covidiots') refusing to take vaxx, for freedom, of their, personal choice vs the rest saying that you have no choice because you 'spread covid' willingly and compromise other's lives around (selfishly, as they said and not 'for the common good' 'of all -- 'to protect all' against virus; but only 'for yourself/your own body....fck the others...'); and you live in society; so you must co-operate (in it/with others, for you are a part of it/you cannot 'exclude yourself' of it, as independent) --or, be evicted/banished from the society, as outcast refusing to submit to the majority's will. majority vs minority.
Majority vs Individual.
So what rights or (single?) right ..do you have (anymore)...as 1, individual. It seems, you don't ahve any anymore. Only Majority / Collective Rights (supplanting, personal/individual right).
I am truly 'in the middle' (am apolitical) and 'meet me half-way'...moderation. Center. Don't make waves.
Thanks for reading,
Just a 2 cents.
PS: LEV is the holy grail, sacrosaint-thing, it will change the world, if AI, is the step to it; then that is the best thing that could ever happen to humans. I have never believed in anything more in my life, than this (and am catholic..can you believe that...if you believe, that/this, in the 1st place). We are at a cross-road Science vs Religion...''stay in the know....or be abandonned.''; ''adapt or perish..''. that is mother nature in its most primal form (as darwin said it). We have to survive. Or like that BeeGees 70s song : ''Staying Alive, Staying Alive....ah ah ah...Staying Alive.... Staaaaying Aliiiiive......Everybody, Must Stay A-Li-E-ve....''.
PPS:
Tehre are too many fatalists and selfdefeatists....it's not so much nihilism or pessimism, it's being Over-Realistic; Overt-realistic....let's be 'realistic enough' (and not dream in color neither). If you continue to believe (and say/repeat) : ''We die...nothing we can do about it...take supplements, calorite restriction, exercise...do your best...and then, close the curtains.''.
Then, no, LEV, will not happen anytime soon, because fatalism and self-defeatism is a killer' for 'funding'. And funds, are needed, to make LEV happen anytime soon. Lots, lots and lots of funds. The more people Belive in LEV/reversing aging and Defeating Aging -- as not some fairy tale/bs pseudo science/outlandish joke -- the more LEV has the chance of becoming a reality, rather than stay in the 'annals of 2020s pseudo-science' when people in 2073...look back at 2020s..
and giggle at our attempts (and failures) but admire our attempts 'for trying'. They can know, that we 'had no choice', cause some of us (older), will not/would not reach 2073. This akin to people in 1980s who thought : ''by 2010s...people will use 'flying cars and skateboard' and 'pigs will fly''.
The saying is: ''The more it changes...the more it's the same.''.
If someone over 60 says it....and I'm younger...and reading from someone OLDER...who saw it all before and realized, that no, nothing changed (much).
(not much confidence in things).
And that's what I fear, ...that, in 35 years, it's more the same and LEV is nary-a-sight,to be found.
The chances of that Being the Reality (by then) are much higher than people may think (despite All the Progress happening, including rejuvenation, etc...). It's just the Last/Major Step, like gravitating the mount everest, almost no one reaches the tip/top and for reason, because it'S the tallest mount and so many died trying. And people that say: ''you're complaining and pessimistic...stop, just hope and there is Nothing Else to do...but that...because we die anyway.''.
Well, that's true, but it gets to you after a while...or you must just 'abandon' and lose hope.
PPPS:
Last PS, Partial Reprogramming - will Not - make LEV; impossible, because from what was gathered is that there is a 'residual' effect and 'losing' effect of it...namely, it may reduce 'in potency' as you do it...you cannot Repeat On and On (loop-d-loop-d-loop....and obtain immortality), that's what I understood; I mean, you can repeat..but the effect may seem to reduce in power/result...Result: the effect loses itself..as you repeat it. So, it seems?, that there is 'limit' to 'intervening' in the methylome/epigenome...over DNA/in nucleus. And on Top of That, it was found that Epigenetic Reprogramming Yamana factors...helped the progeroid mice...but it slowed only a bit the Old 'normal' mice (control/wild type) in terms of epiclock reversal; sure, if we Do reverse the clock 40 years behind and Keep it that way...taht Works...but Only if we can/we do; so far, from what I gathered, there is this 'extreme aging' (like progeria) that can happen with this; meaning, if you reverse the epiclock by 30 yaers...you must 'keep at it' daily to maintain- this rejuvenation; so you are Forced to Rejuvnated - each day - or you lose 'the effect/potency' VEry Quickly; like you know the saying: 'greying over night'...well, you could turn to gray over night; if you do not continue to 'reverse the clock - Daily. Of course, with Nanorobots or things that do it 'Daily' - for us, that would solve the problem; until then; reversal may lose its effect rapidly...and you could go back to being 56 years old - almost 4 days later (!!)...that's scary; imagine looking 20, and the next day, 60...but that'S what may happen. Anyway, we will have to see (..won't we).
It's clear, we have to Repair DNA damage - this is Crystal Clear as Needed; not just reversing the epiclock; by repairing all the Y-H2AX/Telomeric/subtelomeric/centromeric/perimeric DNA damage, all the nuclear defects and chromosomal problems we accumulate with age (including Progerin and Lipofuscin, which happens in Accelerated form - in HGPS progeria people who live 15 years only).
@Robert: Aubrey de Grey knows perfectly well that there won't be any LEV or even greatly increased longevity by 2037. The reason he's throwing around these dates is that the field needs more interest and more investors (most of whom are at least middle aged), which is admirable and needed but won't save any of us reading this blog who aren't in their teens.
Here's why:
According to AdG himself, in order to get meaningful life extension you must target all seven root causes of aging at once. This would require for mice trials to start immediately and be successful in four years. Then, all these treatments would have to ace human trials, which means that there would have to be dozens of the latter going on simultaneously for each one of these root causes given that the failure rate of each trial is over 90%. And the treatments must be systemic since applying senolytics to, say, the retina may very well cure blindness but will do nothing to increase lifespan.
However, this is not simply an incredibly long shot but plain impossible since potential treatments for some of said root causes (glocosepane, mithocondria) are still in the early in-vitro phase.
Not only, the bar for moving something from murine models to humans is pretty low so even a "successful" trial might lead to small benefits: thio, which Aubrey raves about, has cured only some cancers in some mice, while senolitycs - which are arguably the lowest hanging fruit given that drugs that destroy senescent cells already exist - have been in human trials since 2018 and they have just managed to improve idiopathic pulmonary fibrosis a little.
I remember when around 2006 people thought that nanoshells would cure cancer within a decade because they had eradicated of 100% tumours in 100% mice. How could they fail? Meat is meat so it was reasonable to think that heat would believe in the same way in humans as it did in mice. Well, it turned out that tumours in people are too dense for the nanoparticles to accumulate in them properly so nanoshells aren't even a small part of today's cancer treatments.
In other words, progress is certainly exponential but we are still far from the take off point of the curve.
Finally, if anyone thinks that I am trolling they are wrong. I really believed all the hope and hype for almost two decades, but the truth is that the pace of science isn't the pace of wishful thinking. I am not sure that deluding myself in the face of the facts is the best strategy for my psychological well-being.
Maybe in two or three decades there will be treatments (More effective senolytics? Partial epigenetic reprogramming? Stronger cancer therapies?) that will grant some of us another couple of decades, but personally I have resigned myself that I will die. If I am lucky, by then cryonics will be scientifically advanced and logistically accessible enough to offer me a chance, however small, to see the future that way.
*"We will reach Longevity Escape Velocity (LEV) in the next 15 years. Your job is to live healthy enough to intercept those technologies coming your way.
How will you change your diet, exercise, sleep, and mindset to intercept these coming breakthroughs?"*
The above is a Tweet from Peter Diamandis from September last year.
@Barbara T I am not sure that deluding myself in the face of the facts is the best strategy for my psychological well-being. that is exactly my point too. i spent years listening to aubrey saying he thinks the first person to live to 1000 is alive today, and that we were going to reach lev in 20 years etc, but in recent years i have become smarter to the facts and understand how regulation works etc etc. and yes my head has been royally messed up with all this speculation and hype which has confused me and left my mental state in ruins. i only follow the news feeds on here and a couple of other longevity blogs once a week and if something looks interesting i will look into it. i do my own routine such as taking some supplements that have some promising human data behind them (glynac, novos core etc) also exercise daily and watch my diet, but im not pinning my hopes on any of the big stuff until i have seen it with my own eyes.
@Steven B.
Peter Diamandis, Aubrey de Grey, even David Sinclair now, they sound like astrologers.
It's good advice to take care of one's health but it does not mean that we have a shot at becoming 20 again. Thirty years - let alone 15 - are not enough time to do all the work that needs to be done to reverse aging comprehensively rather than partially and only in a couple of organs, no matter how much money you throw at the problem.
The truth is that these prophets sound like Jehovah witnesses: they hint at being in the know but don't explain how we can get to the elusive LEV step by step; when one of their dates passes without anything happening they just chalk it up to a calculation error and whip out a brand new date to draw in acolytes.
I would love to be made to reconsider, but it would have to be through a factual explanation of how we can get from a stage where we have one small trial that has doubled remaining life expectancy in mice (the equivalent of 10 years in humans) with a technique that is likely to cause cancer, to a point where a 70 year old can spend a couple of nights in a clinic and come out his 30 year old self.
@ scott emptage
I feel I would have taken better decisions if I had had more sense of urgency in life, a lack of which I partially blame on this conviction I had that I would live to 150. Like you, I try not to hasten my demise by being sensible about my health, but I also don't think that any of the hyper-preventative stuff pushed by the aforementioned financially motivated gurus (think whole body MRIs or continuous charting of your metrics) would add any significant benefit to a healthy lifestyle.
Even curing all cancer only adds 3 years to life expectancy, so catching an early cancer through MRI, which by no means gives you the certainty of curing it or that it wouldn't have been cured if you'd caught it through conventional means, would add very little, especially if we factor in what it takes away through stress and anxiety and legit medical harm when every little innocuous spot is biopsied or blasted with radiation for further imaging.
People can only live with hope - that's the purpose of religion. Personally I have more hope in the advances that cryonics will make over the next few decades with regard to preservation, even though I know that it's still a very long shot. At least I won't be pinning my hopes on some "breakthrough" just to have them dashed when the fog clears and it becomes clear how stupidly far we are from what we've been promised.
I'm really surprised at some comments in this thread like "returning back to 20 overnight" etc. Of course that won't happen anytime soon! All we can hope for is those elusive "Bridges" that give us 5 yrs, then maybe another 5 and so on. Keep adding yrs and before you even realize it LEV has arrived. As the author Steven Kotler recently stated, your mindset is so important when it comes to health.
@Steven B:
The argument is flawed: LEV isn't some magic state after which nobody dies anymore. Adding 5 years to someone who is biologically 75 will keep them 75, an age during which mortality is high. In other words, the cumulative probability is that you will die after you've crossed the third or fourth bridge.
When these gurus talk about rejuvenation they sell it as something that will make you strong and vigorous, not something that will keep you old for 20 years longer.
What I am saying is:
1) Comprehensive rejuvenation of the type Sinclair and de Grey talk about will take 50+ years if we are very lucky;
2) Only people young enough to have low baseline mortality will cross enough bridges to see a time when comprehensive rejuvenation is feasible.
3) There is a psychological bias that makes people believe that just because they stayed alive easily until 60, it will be as easy to stay alive in the future.
Having said that, I do agree that in two or three decades life expectancy for someone who takes advantage of the latest discoveries could be 100 - so basically 100 year olds will die of the same things 85 year olds die today. But this is a far cry from what most people on this blog and the wider community believed it would happen.
As for the mindset, it has never kept anyone alive beyond their biological expiration date.
I'm quite positive that we will have proper rejuvenation very soon.
Just look how little money was spent and how little time it took to make all these great working anti-wrinkle products available for the masses. Why would it be different for other rejuvenation products?
Especially now that George Church is involved. Man... I still remember so very fondly the time he resurrected the woolly mammoths and tasmanian tigers.
@Jones
Haha, until I got to the mammoth part I thought that you were serious. I wish someone disproved my negativity by pointing to facts I am unaware of, but alas.
@ Barbara,
I remember about 5 years ago some negative " Karen" got on the comment section here and said, " no, it will never work. You're all dillusional " Many of us responed with positive arguments. BTW, you also responded back to this person until she went away. Hmm, maybe that person is in fact " you".
This is my last comment, but following Reason blog since inception, Ray K, AdaG, and other longevity news in past 2+ decades, I can see the trends. You can believe what you want and I believe what I want, and finish:)
Very good comments from Barbara T, which confirm exactly my point.
@ Robert, ahaah! That Karen was probably me and, as you can see, I wasn't wrong. See you in another 5 years (if I'm lucky!)
@Robert:
I remember responding to that person. In fact, there were two of them, one was called MsKaoshin and the other Dog-something. All I can tell you is that no, I am not them - I just began to look at the evidence with a critical eye instead of wishful thinking and came to my senses. But yes, ultimately this is a question of faith and we are all entitled to believe what we want.
"I wish someone disproved my negativity by pointing to facts I am unaware of, but alas."
I think most of us here would agree that unless Dr. Fahy's results scale up very quickly in the next few years (also possibly Katchers') that it is unlikely that most of us here north of 60 would live to benefit from epigenetic reprogramming. (Those say 40 and under a different story.) If his (Fahy's) work does pan out & became available to myself I would give it even money that I would live long enough (say ~30yrs more) to benefit from the 2nd generation tech like the re-programming.
re: Katcher. We have been tinkering with blood factors since the 2005 Stanford parabiosis experiment and we are not even in human trials yet despite the proposed treatment being delivered by a cheap, safe, low-tech method that has been in use for a century. Also, Katcher's results aren't extraordinary and, according to Steve Horvath, treatments are still a long way off and "will emerge" in "the next 20 years."
So it's 40 years between the first mouse experiment and the clinic for a therapy that, if it works at all in humans, might add a couple of years to life expectancy.
Given how translational research works, why are we expecting much more complicated stuff like epigenetic reprogramming to succeed and have great results in a decade or two? Producing tens of thousands of academic papers is meaningless if we don't get rid of the translational bottleneck, and there is no evidence of exponential progress with regard to the latter.
Honestly, anyone who is over 20 should look into cryonics. Those of us who live in Europe may have a chance too thanks to Tomorrow Biostasis, a new German company with partners in Switzerland where it is easy to get euthanasia and therefore good cryopreservation.
"re: Katcher." So Barbara T. what are your views on Dr Greg Fahy's work on Thymus regeneration? He got measurable reversing in ageing on human test subjects using three over the counter available meds. Grant you his test subject pool was small in the original test (9) but about 50-60 in the follow-up currently running. Not only was there measurable age reversal by multiple DNA methylation clocks but in addition observable effects in some test subjects. Things like hair darkening becoming thicker etc. If these results pan out no way it would be anywhere close to 30yrs before it would be generally available to all who wanted it. Probably why big Pharma has largely ignored it; no easily patentable product so no money for them. Might be just the ticket to keep a currently 60 something alive until 2nd gen tech was ready.
"anyone who is over 20 should look into cryonics"
I assume that allot of progress has been made in so called "cryoprotectants" to prevent ice from forming during the freezing process and damaging cells tissues etc.? Thought that was the big hold up with cryonics the questionable optimism of hoping that future nano-tech or something would be able to repair the freezing damage.
I think the Fahy trial looks good, but how much life extension you get from improving your methylation profile is an open question. For example, the epigenetic age of the treated Katcher rats was 54% lower than the controls but the increase in their lifespan was only 10%.
But of course, if the results for TRIIM-X keep looking good I guess that there will be clinics offering the protocol in the future.
My objection isn't to a particular intervention being able to offer some modest lifespan gains here and there, rather to the belief that in 20 years time we will have aging under control. LEV is as much a real thing as quantum immortality: LEV is a theoretical argument, not a date in the future that we must strive to reach. At population level - assuming that life expectancy starts increasing one year every year that goes by - the risk of death for a 75 year old would be still very different from the risk of death for a 25 year old.
Real LEV is when you rejuvenate a 75 year old to the point where they have the risk profile of someone with negligible senescence, but given the sheer amount of damage you need to fix at old ages as well as the pace at which trials are moving and can move, it is not realistic to believe that this will happen in 20 years.
Have you noticed how rejuvenation is always two decades away? That's because 20 years is still far away enough into the future to be realistic on paper but not too far away to be of no interest to the reader. In practice, I think 50 to 100 years is a much more sensible prediction even though it is not what any of us wants to hear.
Re: cryonics. It is a super long shot and while there have been improvements in cryopreservation (preservation of a small mammal brain in 2016, large brain in 2018) there is no guarantee that there will ever be perfect preservation, let alone resuscitation.
Yet, I think that psychologically cryonics is the best anxiety-reducing option for those who aren't keen on dying because it doesn't entail constantly trying to divine the news about this or that "breakthrough" just to be bitterly disappointed when it doesn't work out or falls off the radar (think about nanoshells, Bill Andrew's Libella, Liz Parrish's gene therapy etc.)
I don't like living with these constant highs of hope and lows of depression, with the lows and the stress becoming more prevalent as I get older and start running out of time.
With cryonics you just need to organise your death. In any case, if you get run over by a bus or drop dead from a heart attack you won't realise what happened so it doesn't matter. And if you manage to get properly suspended, wherever the science goes after can't make you anxious because you are dead.
I guess my point is that cryonics is already here and, provided one has the funds, it could be used tomorrow if needed.
Hoping for rejuvenation means endlessly waiting for some treatment to become available. And even after receiving the treatment, we won't know whether we'll live any longer since there is no proof that epigenetic markers predict death once they have been messed with.
This is too much long-term insecurity for me. It's easier if I plan my life around dying at 85 and having everything in place to have another shot at being young in 100 or however many years time. I am looking at doing a mental health survey of rejuvenation hopefuls so I may reach out on this blog in the future.
"Bill Andrew's Libella, Liz Parrish's gene therapy etc.)"
Yes Barbara T. I agree that Bill Andrews telomerase therapy (Libella) is/was a colossal disappointment in a field full of such. Whatever happened to him/it? He also made (or was in) a movie with Aubrey De Grey in it a few years back as well. As for Liz Parrish her gene therapy seemed to be a "success" for herself (your hear from her occasionally) but as you say no word on when/if it will be available to us serfs...probably no time soon.
I admit, it's pretty sad to see the comments here are so universally negative. It seems there's been a real change of heart around this place in just the last few years for this to be the case. I wish Reason or DeGrey would weigh in to comment. It speaks to something significant that this has become the most common outlook at a place like FightAging, when the reverse used to be the case. Note that I am not disagreeing with any of you, and merely observing the sad state of affairs.
"It's easier if I plan my life around dying at 85 and having everything in place to have another shot at being young in 100 or however many years time. I am looking at doing a mental health survey of rejuvenation hopefuls so I may reach out on this blog in the future."
Cryonics..."long shot" indeed; not only if said nano-tech will be developed but also rather they would choose to use it to revive the "dead" frozen people. That might not be very high on the future folks' priority; they would rather spend your money that you set aside to preserve you than use it to revive you. Also on the subject of low probability "long shots" hope you don't wake up ~1000yrs from now surrounded by disconcerting (terrifying) looking UFO "Greys" with their big telepathic eyes scrutinizing your newly thawed body for spare parts/food/some sort of biological raw material that interest them. Good luck to you!
@Ben: I think it's easy to be optimistic when you have no failures to look back on, which was the case when this blog started. Twenty years on, the field is littered with corpses and the hopefuls are getting older as well as more knowledgeable about how long it really takes to move something from mice to humans. Also, about how results in humans are never as good as in mice (e.g. dasatinib + quercetin, various cancer "cures" etc.)
I still think that advocating for rejuvenation is the decent thing to do even if I won't benefit from it, just like opposing wars and climate change, but psychologically for me it is best to stop following the news and instead make other plans. Then if blood transfusions or whatever manage to turn Katcher into Kutcher (as someone on Reddit said) I will very happily eat my hat and listen.
@Tim: it is not about the odds of being revived versus the odds of having my life extended bit by bit until I can get properly rejuvenated - neither of which can be quantified, by the way.
It's about the stress of hanging on to every morsel of hope that comes out of the sensationalistic press (and attention hungry scientists) while I am slowly disintegrating into old age.
Both cryonics and rejuvenation aren't more real than religion at the present stage, but I find the former less anxiety provoking because all that it entails is one single leap of faith instead of the rollercoaster of hoping that this or that treatment pans out.
Will the folk at Alcor or Tomorrow Bio keep my money instead of waking me up? Possibly. Will there even be a world with flash and blood people walking around or will AI have taken over and turned us into hologram slaves? Also possible. But none of this is something I need to worry about now.
Again, it's psychologically less taxing than the alternative without conceding that permanent death will necessarily happen.
I'm so confused seeing Fahy mentioned so often.
His 'protocol' is nothing more than growth hormone with a bit of ancillaries added to mitigate assumed risks. Growth hormone and its secretagogues have been around for quite some time, are widely available and used by everyone and literally his dog of the fitness, beauty and anti-aging crowds. So far no one lived a bit longer than usual or had noticable better immune function. Some look 'younger' (GH->IGF1->skin, hydration state, etc.), but that's about it.
Anyone can try this NOW with very little risk.
1987!!! -> Effects of growth hormone on the adult canine thymus
https://www.researchgate.net/publication/19572204_Effects_of_growth_hormone_on_the_adult_canine_thymus
The ability of bovine growth hormone therapy to stimulate regeneration of age involuted thymus glands in adult dogs was evaluated. The thymuses of growth hormone treated dogs regenerated, resembling thymic tissue of young dogs. Some of the thymuses of bovine serum albumin treated control dogs also regenerated, but only 2 of 5 control dogs had marked regeneration. White blood cell counts in peripheral blood were not different between groups. Serum thymosin alpha 1 concentrations were not different between groups, but decreased in each group during the treatment period.
So... in humans this will be different, right? Because of a bit added DHEA, Metformin, zinc and Vitamin D? LOL?
@Jones. Oh wow, so no effect despite a rejuvenated thymus.
I agree that if these substances contributed to longevity we would have noticed by now, and the same goes for resveratrol, sirtuins, fisetin, metformin, blood transfusions, diy gene therapies etc.
At most they can add a couple of years of extra life, but thinking that together they will bridge anyone to immortality is naive. In fact, the beneficial effects of single treatments can even cancel each other out.
We'll get properly rejuvenated only with radical interventions at the molecular level that literally reassemble cells, tissues and organs back to the way they were when young.
But that's stuff for the 22nd century.
As an aside, I wonder whether all these youthful looking scientists with a vested interest in the success of the aforementioned therapies are so because of the pills they ingest or the botox they inject. Just sayin'.
@Barbara T.
'Oh wow, so no effect despite a rejuvenated thymus.'
GH promotes cell proliferation directly or through IGF1. There is that. It also promotes lipolysis. So your aged 'fatty' thymus looks a bit denser after GH treatment reduced the number of fat cells in its tissue. Voilà, rejuvenation!
Wrt youthful looking scientists... they don't get much sun in their labs. 😋
The truth is NONE of us know when significant rejuvenation or LEV will occur, including scientists. There are just too many unknown variables to predict future technological advancement.
The only thing we can do is try to promote longevity research as much as possible and work on our own personal longevity as much as possible. Perhaps this will result in a 70% chance of middle-aged people here making it to LEV, or perhaps it will just be 3%. The point is if your house is on fire you still try to do whatever you can to save yourself/others, no matter the odds.
And as far as getting your hopes up and dashed goes, this is only psychologically painful if you adopt a certain mindset. One can train oneself to not get one's hopes up but still keep learning and taking actions (For example, I got rejected dozens of times before getting my last job, but after the first few times I learned not to let it bother me much.)