Manipulating the Epigenome Can Drive Aging and Reverse Aging

Researchers developed a system called “ICE” (inducible changes to the epigenome) in DNA reparation, which actually advances aging, and also discovered that the process can be reversed by using OSK-mediated rejuvenation. Using the ICE system, young mice have aged quickly, but with dire consequences on the tissues in their bodies.

Journal Cell – Loss of epigenetic information as a cause of mammalian aging

• Cellular responses to double-stranded DNA breaks erode the epigenetic landscape
• This loss of epigenetic information accelerates the hallmarks of aging
• These changes are reversible by epigenetic reprogramming
• By manipulating the epigenome, aging can be driven forward and backward

All living things experience an increase in entropy, manifested as a loss of genetic and epigenetic information. In yeast, epigenetic information is lost over time due to the relocalization of chromatin-modifying proteins to DNA breaks, causing cells to lose their identity, a hallmark of yeast aging. Using a system called “ICE” (inducible changes to the epigenome), we find that the act of faithful DNA repair advances aging at physiological, cognitive, and molecular levels, including erosion of the epigenetic landscape, cellular exdifferentiation, senescence, and advancement of the DNA methylation clock, which can be reversed by OSK-mediated rejuvenation. These data are consistent with the information theory of aging, which states that a loss of epigenetic information is a reversible cause of aging.

Nearly 200 Companies Working on Aging Reversal and Dozens on Epigenome Modification

24 thoughts on “Manipulating the Epigenome Can Drive Aging and Reverse Aging”

  1. The epigenome is the set of chemical modifications to DNA and the proteins with which DNA is associated that can turn genes on or off. These modifications do not change the underlying DNA sequence, but instead affect how cells read the genes.

    Recent research has shown that manipulating the epigenome can drive aging and reverse aging in various organisms, including worms, flies, mice, and possibly even humans.

    One way that the epigenome can drive aging is through the accumulation of epigenetic changes over time. As cells divide, the epigenetic marks on the DNA can become disrupted or altered, leading to a decline in the function of certain genes. This can lead to the development of age-related diseases and the overall aging of the organism.

    On the other hand, reversing these epigenetic changes can have anti-aging effects. For example, scientists have been able to extend the lifespan of certain organisms by removing or reversing specific epigenetic marks.

    One promising area of research in this field is the use of drugs called epigenetic modulators, which can target specific epigenetic marks and potentially reverse age-related changes in the epigenome. However, more research is needed to fully understand the potential risks and benefits of these drugs in humans.

    Another way that the epigenome can drive aging is through the formation of senescence-associated heterochromatin foci (SAHF). SAHF are regions of tightly packed chromatin that form in senescent cells, which are cells that have stopped dividing. The formation of SAHF can cause the repression of genes that are important for maintaining healthy tissue, leading to the accumulation of damaged cells and the development of age-related diseases.

    Additionally, it has been suggested that the epigenome plays a role in the aging of stem cells. As we age, our stem cells become less able to repair and regenerate tissues. This is thought to be due in part to changes in the epigenetic marks on the genes that control stem cell function.

    On the other hand, reversing these epigenetic changes in stem cells can lead to anti-aging effects. For example, scientists have been able to rejuvenate stem cells in mice by removing specific epigenetic marks. This has led to the regeneration of damaged tissues and a reversal of age-related diseases.

    Another promising area of research is the use of epigenetic therapies to treat age-related diseases. For example, some studies have shown that drugs that target specific epigenetic marks can slow down the progression of cancer and other age-related diseases.

    In conclusion, the epigenome plays a critical role in the aging process and reversing aging. Manipulating the epigenome has the potential to provide new insights into the underlying causes of age-related diseases and to develop new therapies to treat these diseases and reverse aging. However, more research is needed to fully understand the complex mechanisms at play and to develop safe and effective treatments.

  2. I’m all aboard the age reversal wagon. But, the only way it works out is if it’s available to EVERYONE. There would need to be mechanisms in place to ensure that not only the middle to upper class in societies can utilize it.

    • Not realistic. The wealthy will have first access to any meaningful life extension techniques.

      Over time, it will be available to more people down the hierarchy.

      Follow the money, as usual is the most predictable filter.

      • Agreed. The free-market and trickle-down socio-economics, though morally repuganant, is the only thing that brought us past steam engine technology/ industrialization to the current day, in the rich world anyway. And since small town people, luddites, and other such ‘supporters of humanism (in the sense of technology as our tool not our Purpose)’ have almost-all moved into cities and other bastions of technology and productivity voluntarily in the rich world, it is universally accepted as a reasonable means to an acceptable ‘end’.

  3. Treating aging as a disease?

    “As chronicled in The Hill, under current regulatory rules, drug companies cannot produce products aimed at slowing or reversing aging—instead, they can only create drugs meant to target specific diseases. For decades, researchers have looked at curing symptoms of aging instead of the root causes. By changing the classification of aging to a disease under FDA rules, that opens the possibilities for researchers to really take a novel approach to the concept of slowing human cell degeneration.”


  4. The wealthy are providing a lot of money for antiaging research, but what are the long-term consequences of that?

    “So, if the rich can live longer, the rich can get richer longer, compounding the already imbalanced spectrum of money, power, and control, experts argue in a new Financial Times article.

    “The longer you’re around, the more your wealth compounds, and the wealthier you are, the more political influence you have,” Christopher Wareham, a bioethicist at Utrecht University, tells FT. The science of longevity will only widen existing gaps, he says.”



    • Depends on whether you want a Fair world or a Great world.
      A great world places personal choice above all else – wealth included. If you feel that enabling full personal choice will ultimately destroy or otherwise make miserable the World as a whole, well I guess that could be a thing.

    • “The longer you’re around, the more your wealth compounds, and the wealthier you are, the more political influence you have,”

      So I want to get my hands on rich people’s money so badly that I can’t wait for them to die so the guv can collect it. The fact that I, you, everyone has to die to facilitate that is beside the point.

    • ““So, if the rich can live longer, the rich can get richer longer, compounding the already imbalanced spectrum of money, power, and control”

      Nah, the rich don’t will it all to charity when they die. It goes to their progeny, who keep compounding it. This isn’t like the old days when the wealth was divided between ten children and they could each lose their stake by being incompetent with it. These days it goes to just a few kids while trust funds and asset managers remove most of the risk.

      One of the most widespread tax dodges is inheritance + capital gains. See, if you keep all your money in the stock market, you don’t get taxed as it appreciates in value (even though you get tax breaks on other income using the losses). You might think this doesn’t matter much – you have to pull it out to spend it, right? And at that point the increase in value is “realized” and you get taxed. Unless… you die. When that happens, spouses pay nothing on estate taxes, while for children the first $13 million that they inherit is tax free. They can inherit twice, first $13 mil when dad dies (the remainder goes to mom), then another tax free $13 mil when mom dies. And this is per child.

      It gets even worse when you borrow against your investment holdings, because that means you never have to sell in order to spend. At the time of your death the loan is settled – before inheritance is paid out – so capital gains on that wealth are never realized. Because these are highly secure loans, they typically are charged a very small interest rate – less than the average return rate from stocks. So instead of paying taxes they can pay a bank a couple of percent.

      Death doesn’t make this better, it makes it worse.

      • Oh sorry, I should have specified that I was talking about US federal inheritance/estate taxes. There are states that have some inheritance/estate taxes, and other countries with a variety of systems. But this doesn’t make it better either, because the wealthy can shop around for beautiful island countries to die in that don’t have any inheritance taxes at all.

  5. For the last 10 years I’ve been heavily into the anti -aging scene. I’m 42.

    I’ve taken NMN, NR, AKG, fisetin, krill oil, quercetin, hyaluronic acid, MSM, Metformin, resveratrol, multivitamins, astaxanthin, plasmalogens…

    There isn’t any cycle that I rotate on, I just take what I think would benefit me at the time, with what I’m able to afford. I also practice intermittent fasting coupled with a high protein diet with lots of exercise and sleep.

    I quit taking the NR and resveratrol a while ago because of the lactic acid buildup that was not cool. Other than that I feel great.

    Yeah I might be treating my body like a chemistry set, but these are based on real science, and I know that the REALLY high -tech treatments are on the way in a pill or a shot.

    • It’s one thing to be ‘cutting edge’ anti-aging and it’s another to be top 10% healthy. I recommend you get a ‘total tear down’ assessment of yourself. You may find that one leads to a better chance of succeeding at the other. The Mayo Clinic, etc., have week long ‘total’ physicals.

  6. It’s somewhat disingenuous talking about ‘reversing aging’. I can see removing damage. I can see creating systems/ therapies that create repair strategies that can fix faster than things break/ get used up/ change negatively. I can see switching out/ upgrading old or bad components. But let’s not talk about reversing the ‘arrow of time’, undoing entropy, or other such. You cannot ‘un-rust’ a car or de-age an adult human so they are pre-pubescent or embrionic – probably. Aging is more than just damage – it is development. It is moving from one stage to another (which isn’t to say THAT can’t be done). We are at a critical time when it is best not to make false promises or sensationalist claims – the FDA, public, investors are watching.

    • We do have cells in our bodies that do not age, which is to say they are constantly being repaired and restored. So it is possible. The problem is that these are only certain reproductive system cells. It is necessary or our children would be born old.

      The reason why it is only our reproductive cells is that it takes a great deal of energy to do this. From an evolutionarily standpoint, it was much more economical to grow a bunch of support structure that would be periodically replaced, making it disposable. This would be our bodies. Our bodies are just a gamete’s way of supporting and perpetuating itself. However, our bodies have evolved intelligence, which is us, and we don’t like the idea of being part of the disposable stuff.

      Energy costs are not a constraint anymore, either. So the trick is extending the rapid and near perfect repair of the reproductive system cells to the rest of the body, including our brains.

      Of course, sometimes there are changes or damage to reproductive system cells that result in suboptimal bodies. Evolution takes care of this through a kind of culling (for various reasons, you can’t really refer to it as ‘survival of the fittest’).

      We will probably keep seeking ways to ameliorate even this, in order to push through to the next plateau in defeating death, but first things first.

      • Even the reproductive cells only hold out against entropy because they go through the needle’s eye of reproduction, where all the critically damaged cells fail at their task, and get eliminated. And then the organism gets similarly filtered by life.

        Even the reproductive cells age eventually, but randomly, and those two filters limits the next generation to the ones that lucked out.

        • “Even the reproductive cells only hold out against entropy because they go through the needle’s eye of reproduction, where all the critically damaged cells fail at their task, and get eliminated. And then the organism gets similarly filtered by life.”

          Right, all cells are screened to some extent. Autophagy is important. White blood cells, of which we make about 100 billion per day, have an enormous number that get culled almost right away. But yes, more rigorous testing (and destroying or repairing the rejects) also involves greater expenditures of energy. Evolution determined that the very highest levels of this were only cost effective for reproductive cells.

          But we are willing to pay a far higher cost in energy (with the commensurately greater increase in entropy this entails) to ensure we are kept in tip-top shape from stem to stern. If having to eat 20 or 30 thousand calories a day was the price we had to pay for this, well, I reckon a lot of folks would be okay with that. (Buy stock in ice cream companies if this happens.)

    • Actually, thermodynamics certainly does allow for aging to be reversed. You can roll rocks up hill, chill things in a refrigerator, and so forth. Thermodynamics is perfectly consistent with entropy going down is a subset of the total system, it just dictates that doing so must increase TOTAL entropy.

      Life itself is an exercise in this: You turn low entropy food into high entropy waste products, and capture a bit of the flow to pump down your own entropy. All driven by extremely low entropy radiation from the Sun eventually being converted into higher entropy thermal radiation.

      The challenge is that lowering entropy requires detail work, it is NEVER the default result of an operation. On average, anyway.

      Anything that would reverse aging must be expected to consume energy to drive a reduction in entropy. But that’s all thermodynamics is telling us, not that it’s impossible.

      • I basically grasp what you’re getting at. Unfortunately, my physics background stopped at acquiring the post-Grad background to become a lowish level Engineer; so specific ramifications of the Laws of Thermodynamics, Entropy, most Enthalpy, fluids, most classical mechanics except statics and kinematics, most EM, and relativity/ quantum ideas are but cartoonish concepts in the back of my mind, not considered as part of my day-to-day.
        That being said: my take on entropy is less about energy and more about the likelihood (and inevitability) of disorder and its inability (or vastly increasing effort) to become ordered and thus useful, even if we are getting a vastly disordered ‘surrounding’ in exchange. If the amount of effort (which some may technically call work) is so large compared to the effect of creating a tiny isolated low entropy result, then we are effectively splitting hairs by saying though not impossible, is extremely unlikely. Thus the Parable of the Engineer: Be Practical on the Route to Invention and Discovery.
        David Christian gave an excellent TED talk in 2017 on the universe’s inevitable heat death under explanations of entropy.

        • Yep, some people point to the fact that life on Earth has evolved from primitive chemical reactions into us, and that we, in turn, will take in carbohydrates, fats, and proteins, and produce offspring that may become more advanced than we are as some sort of invalidation of the whole idea of entropy.

          What they don’t see or ignore is the massive amounts of entropy necessary to create and sustain the relatively trivial-by-comparison anti-entropic processes of life.

          But that’s business as usual. Even if we can make it far more efficient, there will always be more entropy than “anti-entropy.” The laws of thermodynamics guarantee it. Nonetheless, if we have to create even more entropy in order to reverse aging, which we will, then it is a pretty safe bet that this a price we will willingly pay, if at all possible.

          It seems unlikely it would require resources sufficient to bring about the early termination of the universe, or even the Sun.

  7. Cool. But I’m a bit weary of these breakthroughs end up producing nothing outside of GMO mice.

    The critters have such short lifespans that they seem to be booby tapped to die soon. Mechanisms that change lifespan on a mouse, are already in place on longer lived mammals like humans, so we get no benefit from them.

    They better show us a 10 years old mouse and then we can get excited. Or rejuvenate an elderly dog into visibly frolicking like a pup again.

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