Age Resetting Genes Going to Human Studies in Two Years

David Sinclair is a geneticist at Harvard and author of Lifespan.

Nature – Reversal of biological clock restores vision in old mice

Sinclair and his team restored vision in old mice and in mice with damaged retinal nerves by resetting some of the thousands of chemical marks that accumulate on DNA as cells age. They are now working to rejuvenate the brains of old mice. This work is so promising that Sinclair believes he can get to human trials within two years. Sinclair is using three genes to reset the age of cells.

Sinclair says taht there are three main pathways or mechanisms in our bodies — our cells that can counteract aging. They sit at the top of a pyramid of defense functions in our body that we are learning how to tweak. He is studying sirtuins. there is also AMPK and mTOR pathways. These guardians of the body exist and we’re learning how to activate them and get them to work harder.

SOURCES- Nature, Inside Tracker, David Sinclair, Lex Fridman
Written by Brian Wang,

78 thoughts on “Age Resetting Genes Going to Human Studies in Two Years”

  1. Hopefully, we won't need to kill anyone. Just outlaw the technology. If that doesn't work then 120.

    But our current religion is the worship of money and billionaires so like sheep we will allow ourselves to be led to slaughter.

    There will only be one choice. Mankind or immortal billionaires. The immortals will not allow a free human race to co-exist with them because of the potential danger we present.

  2. Easy to blame the Elites. But what are the Normies doing to justify their existence? Or is the common person above criticism and need for improvement and having their every action questioned? If we really believed that Elites were so bad, we wouldn't move to their Cities, buy their high tech gadgets, and continue to partake in their health advances. If there were no elites, we would still be living in the 1920 – 1940s where everyhting could be homemade and nothing smart needed to be integrated into a worthwhile life. But hey – people consume tech, covet choice and wealth, and pursue capitalistic/ selfish goals – ubiquitously – and then turn up their noses to anyone else who has not 'made it'. Hypocrisy is rampant. Not wise to bite that hand that feeds you when you really have very little elsewhere to go or eat, frankly, without them.

  3. Agree with Jebz. Semantics matter. Reversal is non-sensical. Intervening so that the cosmetic/ localized conditions have a more optimum state (appear in some criteria to be the same 'in profile' as a creature with a lesser biological age) is correlation and a different idea. i.e: I have an injury. it has healed. Is that part of my body younger? no.

    I am sympathetic to the idea that 'your time before death' is causitively linked to damage, toxin build-up, vital resouces 'used up', and the degenerated functionality of organs — but that all these illnesses (that happened to be statistically significantly aligned with people of a greater biological age) are part of the grand illness 'of aging' is fundamentally disingenuous. Fix the different issues and/or upgrade the current parts equals greater amount of body functionality, likely means 'time before death' increases, even years of healthy usefulness 'increases'. That's it. You can sell it on that. I think that you'll find that most people would be very happy to extend their current functional lifestyle, but when re-phrased as 'do you want to live forever' – the crazies and traditionalists start to rant and obstruct and put forth isolated and cult-flavoured 'grievances'. Not worth it.

  4. Meh – such is the verbiage of the mainstream. Many political and cultural issues to deal with even before assessing the science. To me, the big one is availability, if treatments that extend the currently-agreed 'health-span' are many -x- $10k per month and unavailable through most insurance — the number of people with access to extended health will be tiny. Public pension plans will scream. AARP will scream. Woke wealth-re-distributionists will scream. Consider the new alzheimer's therapies of many $1ks per month – inaccessible to all but top 5%. Scream.

  5. But at what age would be people be legally required to step into the government gas chambers?

  6. This research is based on using OSKM factors to reverse the epigenetic marks of aging which are frequently called the "Horvath clock" or "Horvath epigenetic clock", named after their discoverer (Steve Horvath). These epigenetic changes correspond closely both to chronological and (it seems) to biological age. Exciting and surprising results have been obtained by changing an aged organism's epigenetic "backward", such that an old organism has the epigenetic profile of a young organism. Of course, there is debate whether the Horvath clock is merely an epigenetic response to aging (e.g. a response to intracellular damage), or whether it is an upstream and primary cause of aging. Several proponents of the view that the Horvath clock is a far-upstream driver of aging also hold the view that aging is largely a program of some sort.

    Regardless, in the case of this particular article, calling the goal of David Sinclair "reversing the clock" of aging is not scientifically misinformed.

  7. At a wild guess, a fair amount of energy is used in the digestive process itself.
    If you stop using that you might "have more energy" available, at least on a short term basis.

  8. I suspect the world is hardly going to get less diverse when people can live as long as they choose.
    So yes. Some places will outlaw arbitrary aging. Today you already have mormons, north korea, Saudi Arabia, Santa Monica CA, Tokyo, etc (etc etc), all on a single planet.

    Curing aging, culturally, is not going to make things simpler and less divergent.

  9. Not sure what you are saying. But the elites are already doing whatever it takes to expand their power. I doubt immortality will decrease their appetite for power.

  10. I suspect that killing immortals will be the in thing. And I fear there will be no peace between them and the rest of the human race. In the end, I expect immortality will be outlawed to maintain peace.

  11. The "Tree of Life" is guarded by the Cherubim with the flaming sword. I take it as a warning that should be heeded.

  12. It looks like he had some articles on the subject in 2018. Agreed, it would be nice to have an update. For a lot of people, this is the most realistic option.

  13. hard to wrap my head around the idea of : increased energy with intermittent fasting. Once you have all your essential minerals/ aminos, all energy is positive with maintaining/ re-building. I assume that energy inflow is nearly zero-sum – the more energy, the more benefit. Poor food choices will debilitate you, of course, but depriviing yourself of 'quality' energy seems counter-intuitive. I know many of the anti-aging websites speak of 'fasting' along the same level of impact as exercise, etc., but conceptually flawed, methinks. Even if it only about the cellular 'signalling' that happens upon reduced caloric intake – a short-term trick. If fasting doesn't help in your 90s then it certainly is a bandaid earlier on.

  14. Dermatology is one of the most prominent areas of non-neural, non-heart research. Great stuff coming out of castle Bioscience, etc., for assessment.

  15. Yes. Yes. Intervene Immune is designing human trials per your comment. A few programs, such as U.Pitts and something in LA is including it with other organ regeneration research. Not sure why I thought that the thymus was more accessible than being above the heart. Perhaps an alternative source of thymocytes can come from elsewhere. External sources of such immune-beneficial t-cells from an artificial in-vivo source/ supplemental therapy?? This and senescent clearance as an ongoing therapy is my biggest hope for an extra 20 years of driving and an extra 30 years of non-bedridden living.

  16. I'm expecting melanoma rates, at least, to drop drastically soon; My generation were very casual about sun exposure, we were unaware that sunburn was more than an acute problem that went away in a few days, that it could come back and bite you with skin cancer decades later. I lost track of how many severe sunburns I got as a child, several a year, at least.

  17. Of course, there's Fahy's research on thymus regeneration, it actually does appear to be feasible. The main obstacle his research faces is just that one of the drugs is legally prohibited from off label use, (Human growth hormone.) so you need government permission to even do the research.

  18. regulations have held this back (and mediocre tech) . Point of death requirements before whisking you off to your multi-generational stay in a hot water heater tank of vitrified destiny. Best to pass in Flagstaff, I guess.

    Brian: Go interview Alcor to see where vitirifcation and revivification is at.

  19. possibly an in-between idea: not fixing yourself with the same parts so much as incrementally upgrading as you go. Whose to say that the molecular engines of life, immune system interactions, and senescent cell clearing systems can not be switched out with better models. Same idea, improved material, etc. A cyborg at the cellular level. Mechanical hearts? why not bio-mechanical cells?

  20. Reasonable. Though I wonder if a certain mildly-deficient level of health, lack of annual check ups (who got those in their 20s?), and a certain lack of attention to moderate hygene/ activity necessarily increases 'asymptotic' cancer risk potential. Of course, expecting to be in the top 25% of physical health right out of one's teenage years may be much to ask — but interesting to see how background health affects 'the odds'. I guess that I struggle with the idea that some cancers are just utterly random.

  21. I'm sure you can find the 'balance'.
    Hmm… if I eat this 24oz steak and 1/4 pound cheese cake, how far will I need to run, detox, purge, etc. Your health is your bank account. Just keep it black.

    To me: the easiest way is to have an 'overcompensating' regimen done by the time you get to work… every M-F only – get up at 6a, eat your tasteless oatmeal, anti-oxident fruits, probiotics, and juice; do your 45 – 60min of high intensity cardio, non-failure strength, and minimal stretch/ flex training. Roll in to work at 8:30a. Have a tea — and no caffeine or sugar until 12-noon. After that. Its your own choice – reasonably. You have likely overcompensated for all future destruction. Besides, it makes the regimen easier if I can reward myself after 12 and on weekends with whatever slathering pile of spicy pork/ prime-rib/ flesh, drooling chocolate/ cream/ butter/ cheese, and over-alcoholized craft beer i want. Pre-health.

  22. "… there isn't any fundamental reason why repair processes can't more than keep up with damage…" An interesting concept. What does it mean to be repaired 'better than new'? – or is it just identifying each and every damage scrap and eliminating it immediately. I am of the opinion that just because something is not physically impossible that does not make it anywhere near plausible or likely. The key is to identify the earliest steps to 'proof of concept'. Is there such a path? The various scales and unpredictability of repair locations make it unlikely that such comprehensive and just-in-time action of monitoring, intervention, and re-check could be undertaken while still living a rich and full (and not absurdly poor) life. Can you imagine trying to chase all the cancer cells of a metastisized pathology?

    Re: ".. connectivity in the CNS relies on meter long cells that grow in infancy, and are never replaced…" Agreed. Some things just run out, such as the thymus or your adaptive immune (as opposed to innate immune system). My sense is that we would not still be human if we retained many of these things that may or may not have been more appropriate at various 'phases' or our existence (i.e. pre-pubesence, repro-age, post-, etc). Per above, I am not sure we are up to 'the chase'. Better to have a more robust system than constantly fix the current configuration in an unending and accelerating battle.

  23. The sort of lymphoma I had is usually asymptomatic until it has started spreading; As I said, the oncologist said it's usually only detected at stage 1 if you have a chest x ray for some unrelated reason. It goes from barely detectable to "he's dead, Jim" in the space of a few months.

    Then there's melanomas occurring on your back, where you can't see them. I get regular skin surveys due to a history of sunburn and my sister dying of it, but it's quite easy for somebody to not know they have one if it doesn't pop up somewhere obvious.

    So, yes, it's quite easy for somebody to go to stage 2 or three on a cancer without knowing they have it. it doesn't require being horribly oblivious.

  24. I can personally recommend intermittent fasting, it was unpleasant for the first week, but my energy levels are much higher now, and, really, after the first week it wasn't any big deal.

    But, aside from the weight loss and higher energy levels, I won't be seeing my blood work done again for a few months, so you've got a point there.

  25. Theoretically, there isn't any fundamental reason why repair processes can't more than keep up with damage, so that the amount of damage declines over time to some negligible background level. No law of physics precludes it, it's compatible with the laws of thermodynamics, and there are in fact living organisms which do not appear to age, at all.

    The problem with this in regards to our current biology are kind of long term. For instance, long distance connectivity in the CNS relies on meter long cells that grow in infancy, and are never replaced. We simply have no mechanism for replacing them as they die from random events like strikes by cosmic rays.

    Or what you might cal morphological drift: Even if you heal, you don't necessarily heal to the exact same shape, and gravity is pulling you down, like a statue crafted from tar. From your twenties to your 80's you lose inches of height, and that's not all due to joint wear, your actual skeleton is changing shape under the relentless force of gravity.

    So, even with perfect repair mechanisms, you'd lose functionality of the CNS in a few centuries, and eventually end up a pancake…

    Both of these could, in theory, be addressed with artificial mechanisms utilizing molecular nanotechnology, and I'm going to guess nobody is going to squish into a pancake before that's invented.

  26. Funny how this blog hasn't talked about cryo that much… vitrification… head storage.. prep for post-death survival and revivification success… alcor seems a great anti-aging hedge…

  27. I guess I have a hard time believing that someone could be so out-of-tune with their body and current annual check-up protocol and sensible lifestyle choices that cancer could just side-swipe them like that. I can see that many may not know their family's history or all the little chemicals they may be subject to living in some industrial town in Penn by the coal seams, etc. But 9 out of 10 Stage 2/3+ cancer diagnoses are likely negligence on the patient for not acting on some tell-tale sign or just indifference to regular monitoring…

  28. reply-attention-bait. Don't fall for it. No one is so simple as to believe this -or- that cyncial and still functional..

  29. Agreed. localized repair or larger-system (organ) rebuild or switch-out for better parts are the key. At the end of the day, there is no amount of 'resetting to the configuration as typical of a chronologically younger' creature is the same as immortality or current life-span +50%. There is never a time when your body is working so well that you are essentially immortal – just the rate of repair/damage may be appreciably different at different ages (i.e. hey look, I am dying slower)

  30. first associate yourself with a HMO-ish thing that will work with you in gerentology, geriatrics, etc., as appropriate over the years. I recommend Mayo clinic.

  31. Exciting, but I wish that they wouldn't insult intelligence by saying 'reverse the clock' or some other attention-grabbing, but overly simplistic headline. The arrow of time goes but one way. Put a chick back in an egg and I'll believe otherwise. Aging is either accumulated damage, pre-programmed, or a hybrid of the two. You are a rusted car – removing the rust does not make you younger, it just makes you less rusty. Treating yourself to not rust is a thing. Removing rust is a thing. Switching out parts of yourself so that they are not susceptible to rust is a thing. Creating an environment where one cannot rust is a thing. Changing yourself so you are no longer a car is a thing. These are the metaphor for solutions and approaches and methodologies. Please, science-people, just tell it how it is. We don't have to raise awareness or attract the public eye by dumbing-it-down; just get the research, trial, and commercialization done.

  32. Agreed. I would love to get a cholesterol check every other week and see how diet and exercise affects it.

    Currently my doctor tells me, don't eat anything you like, exercise daily, and then come in after 3 months for another blood test and see if anything happened. That's very hard to commit to, and I have no idea what part of that regimen is actually helpful. If I could focus hard on one aspect for 2 weeks, then I would start to build up an idea of what I really need to do to control my levels, and what habits are acceptable.

  33. High resolution skin survey could really be done with a simple camera, maybe in infrared range. You would need to line things up from one month to the next and compare differences. I could see this being done by a smartphone app.

    Smartphone apps are being rolled out in countries that can't afford western medical equipment, for instance ekg monitoring, ultrasounds, etc. You still need some kind of sensor to pick up the images but by removing the heavy lifting electronics and specialized RTOS to run them, it makes the system considerably cheaper, often by a factor of 100 or more.

    It's not done in the USA much because the heavily entrenched medical device companies have a big moat around them, protected by FDA regulations and processes.

  34. I actually directly addressed the cost issue. That could be dealt with by mass production and more efficient utilization. I believe $10 MRIs are a perfectly feasible target. The cost of MRI's is being driven sky high by availability limits, certificates of need to buy them assures a shortage.

    And we ARE talking screening here, not tests that would result in anything beyond a closer look.

    The chief reason for opposing large scale screening is that the cheapest treatment is a death certificate; Hospice is cheaper than chemotherapy. 

    The fact is, cancer is highly treatable at this point, if caught early. And it's getting more treatable all the time.

    There are some arguments about the value of screening for really slow growing cancers, like my prostate cancer: More men die "with" prostate cancer, than "of" it. (But the men who die of it, die horrible, horrible deaths.)

    But, as a general rule, the sooner you catch it, the better.

  35. the heck it was. by that point everybody should be dead by 30, when their most creative innovative years are behind them.

  36. “There's no real reason” ??!!
    How about cost?
    And false positives…… a major problem with large-scale medical screening, and the reason that there are usually strict criteria for when screening is appropriate

  37. Not only that but an almost inarguably superior balance of motivation and moderation, specifically because of the awareness that time is on their side.

    It's easy to mistake curing aging as a bad thing for many reasons. But those reasons are all based on a history of aging being involuntary and often random.

    Ironically enough. Because it makes everyone who argues that way, overly *conservative* servants of thousands of years of pro-aging tradition.

  38. Ridiculous exception is the small intersection of both agendas. E.g. hair loss.

    Which goes to show that it's all vanity. Not genuine altruism.

  39. Lot of variation between high end and low end scanners, in terms of speed and resolution. Pushing both up requires really strong magnetic fields, which is the main cost driver.

  40. It was a mediocre movie that actually attempted to appeal to the audience, rather than critics. That usually helps.

  41. If so, expect it to be banned.

    The law in our society has long shown that it is less important to help 1000 older people to be healthy than to prevent 1 professional athlete to get an "unfair advantage" in playing a children's game for an audience.

  42. Old people ARE a lot more conservative (in every sense of the word) than younger people.
    But is this because you naturally become more conservative when you have more experience? Or you become less adventurous when your hormones shut down and you become weaker and less able to recover from setbacks?

    Because if it's the second explanation, then a 150-year-old with the body of a 25-year-old might have a 25-year-old's level of innovation and risk taking, but with much more knowledge, experience, and likely resources.

  43. They are expensive. The other ones are actually young and cheaper. They are just modified to be fast aging.

    Sure, it raises doubts, but they can run the same tests again on actual old mice if they get a good result. Probably in motion now. Possibly a factor in that, 2 years to start human trials, comment.

    90 week old mice are all the way up to $450 each:
    25 weeks are $80-90.
    Young are cheap like $20. I am guessing the fast aging modified ones are a bit more but much less than the real deal.

  44. For a mediocre movie it seems to have stuck in the public memory for a lot longer time than average.

  45. Of course then you need the scan to be examined to see if there is anything there. Fortunately, our AI systems appear to be ideally suited to such applications.

  46. The assumption that nothing will change, when the single most decisive characteristic of human life changes, is based on… nothing. Because there exists no precedent.

    People, for the measly sum of a few decades of miserable life, have stormed "a few old men's" castles and upended countless "invincible" and often "divinely ordained" status quo. This is all over the thousands of years of human history.

    It is *not credible* to pretend that those revolutions would have been less motivated if not merely decades but potentially eternity had been at stake for the oppressed.

  47. I recently had one on ankle only amd they scanned for 30 mins. Not sure if they were getting extra resolution or what, but I asked if they would do whole body and they said it would take more time so no :(. I assume there is some trade off on resolution vs time. Computing surely can’t be the hurdle now? It makes me wonder if there is some combination scan which could dramatically improve imaging time.

  48. Eh, that was a decade ago, and the nice thing about aggressive cancers is that you're in the clear fairly fast; If it was going to come back, I'd have been dead years ago. I'm now in good health aside from some issues having to do with the chemo having killed every vein that was used for an IV; If you ever go through chemo, and it's possible to get a port, do it. In my case there wasn't time to install one.

  49. Why do they "prematurely age" these mice and then reverse the process when they could just use old mice? Seems like an unnecessary step.

  50. I did read recently (but can't put my hands on the link) of a new study of mechanism for getting the cancer treatment into the effected cells and then triggering it with ECT. Supposedly worked well for prostate cancer, but there were significant side effects with this trial. Also there was a recent study on getting cancer treatments past the blood-brain barrier.
    My point being there are significant advances occurring in cancer treatments simultaneously.

  51. I don't think you could put one in every gym, but you could run people through them like an assembly line. The high end machines cost $3M, mass production could probably cut that substantially. But if you set one up for industrial automation, basically "palatalized" the people in plastic cradles, and fed them through at the maximum rate the machine could sustain, using peak pricing to encourage people to schedule around the clock, you could easily hit 35K MRIs per machine year. Amortizing the cost of the machine over several years, you could get the cost of a scan down to $10.

    I'm betting you could make that even quicker if there were the incentive to build a 'mass production' MRI machine.

  52. Agreed! We treat health monitoring in an archaic way. Heavy equipment on construction sites gets better monitoring and preventative maintenance. I would love to know what mri machine should actually cost if you had one in every gym in the country

  53. You could deal with the cancer largely by vastly increasing diagnostic capabilities; Cancer is usually discovered much later than it was actually detectable. (As in my case.)

    There's no real reason you couldn't have people just routinely getting high resolution skin surveys and terahertz and MRI scans, on a weekly basis, with AI diagnostics. Once you'd established a baseline, the AI could flag questionable changes. It wouldn't require high level AI, just good pattern matching.

    Sure, the equipment is expensive today, but it isn't mass produced. It could be affordable if these tests became routine.

    With cancers routinely being detected at stage 1, the cure rate would skyrocket even with current treatments.

  54. Prostate and B cell lymphoma. The latter being discovered early thanks to the preoperative exam for the surgery for the former. I like to say that getting prostate cancer saved my life… By causing the lymphoma to be discovered at stage 1. (My oncologist told me that when my sort of lymphoma was found early enough to have a good chance of a cure, it was almost always because of a chest X-ray taken for some unrelated reason; By the time you got symptoms that would result in it being discovered, you'd be quite advanced.)

    Actually, the only reason I'd had the chest X-ray as part of the pre-op was that I'd had bronchitis a month earlier, and the anesthesiologist insisted on being sure it was totally cleared up. So I seriously lucked out there.

  55. If the old don't die, civilization will crystalize and become frozen. A few old men will control the world and do whatever it takes to keep their advantage.

  56. I've had cancer. Twice. At the same time, even. Sucked, big time, and I can't say much for the side effects of the treatment, either, aside from that being alive with them is better than being dead without them. (Though that was a close thing towards the end of the chemo.)

    We're getting better and better at treating it, though, and the knowledge they're gathering in this research is applicable to that. 

    I think we can't let the fear of cancer scare us away from these treatments. Getting cancer again might kill me. Getting old WILL kill me. I'll take my chances with anti-aging treatments.

  57. Can't wait to see how this pans out. Sign me up for those trials lol. Of course, it's always curious to me that attempts to reverse our biological clocks could potentially cause cancer (i.e. lengthening telomeres). Which, no thanks, has to be a way to do it without that risk. Then again, breathing carries risk of cancer. So, there's that.

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