OK - another very optimistic person (not quite as optimistic as Aubrey, but still… a long history of being very optimistic (some might say exceedingly so), David Sinclair.
I disagree with David on a lot of things… the value of resveratrol and NMN in fighting aging for example, but I actually do agree that the first person to live to 150 years is probably already alive / born. With a little luck, he or she is also over 50 years of age
Genetics professor outlines recent research on altering molecules that turn DNA on, off, reset cellular aging of body
Aging has been long believed to occur through accumulated mutations to DNA, which gradually interfere with the normal functioning of cells, tissues, and organs. In January, Harvard researchers reported that they’d turned the clock back on laboratory mice by altering the epigenome, a suite of molecules that turn DNA on and off in ways specific to different tissues. Because the epigenome is easier to alter than DNA itself, the finding raises the prospect of being able to reset the body to fight diseases such as Alzheimer’s, diabetes, cardiovascular disease, and cancer, whose incidence increases as we get older. The Gazette spoke with Genetics Professor David Sinclair, director of Harvard Medical School’sPaul F. Glenn Center for Biology of Aging Research, and postdoctoral fellow Jae-Hyun Yang about the work and its implications for human health and lifespan.
Sinclair is also overly optimistic but his optimism and hype has different roots than that of Aubrey’s. The mistake Sinclair does is to assume that aging is primarily programmed by genes and gene expression and that restoring the gene expression to a youthful one with cellular reprogramming is some holy grail that will solve aging. He ignores the fundamental role of entropy in aging. While programming plays a role in aging and reversing it can help slow down or reverse aging it’s not the fundamental cause of aging. What Sinclair and other proponents of programmed aging ignore is the fundamental damages that occur during aging that contribute to aging yet have nothing to do with programming and cannot be reversed with reprogramming. When I mention, to proponents of programmed aging, examples of damages that reprogramming cannot fix I am met with evasion and ignorance. In the case of Sinclair, I don’t know if he actually believes reprogramming will solve aging, or if he is just hyping it up to get more funding. Whichever the case I don’t think it’s good to give false promises.
Different people take different views. I agree with the idea that Gene Expression is at the core of aging, but I think it is moreso to do with a failure of long genes to express (through stalling of RNA Pol II). I think I have found a partial solution to this which I am trying on myself and a small group of other people (at varying levels). I think there is reasonable evidence that this partial solution is a partial success.
It’s not a matter of different views here. Some of the views are simply plain wrong and ignorant. Like I said, I can give examples of things that, even if we would have super advanced technology to reprogram all the cells back to youthfulness state, the things simply cannot be fixed by epigenetic reprogramming. That means it’s impossible for epigenetic reprogramming to reverse aging fully. It will only partially reverse aging.
To give you an analogy of the ignorance I’m talking about. No smart person that knows the basics of how computers work would think you can completely fix a laptop that has damaged hardware (like broken screen, broken keys) by simply configuring or even fully restoring the software. Even reinstalling the operating system won’t fix the broken screen or keys. The reason why is the same as the reason why epigenetics changes can’t fully reverse aging.
I have seen the study on the long genes. It’s interesting. What is quite ironic here is that this problem with long genes happens to be one example of something that can’t be fixed fully with epigenetic reprogramming. Some of the causes of long genes not working are surely epigenetic in nature and can theoretically be reversed with cellular rejuvenation therapies in future. However some of the causes are from DNA mutations and they cannot be fixed with epigenetic reprogramming.
Even if the majority of them are not caused by DNA mutations, some of them likely are. In any case, DNA mutations are one thing that cannot be fixed by epigenetic reprogramming.
I agree with this. If the staĺling is all caused by damage then the cells would be unlikely to function. It is worth reading the stalling paper on some detail.
Whichever cause you believe it is and three options are proposed: DNA Damage, splicing factors or acetyl coa shortage
The long genes hypothesis has a lot of support from different published papers written by people without conflicts of interest (in the main)
Maybe he would describe his views a little differently, but he certainly talks like epigenetic reprogramming is some holy grail that will solve aging and fails to mention all the problems that will never be solved with reprogramming. So either he is being misleading, by trying to convince people that reprogramming is pretty much all we need to solve aging, while simultaneously not believing so, or he actually believes so, in which case he is most certainly wrong.
I’m confident you’re correct that there is genetic entropy that epigenetics/reprogramming can’t fix .
But I’m not sure when such problems would really kick in. Are there attempts to put an upper age limit on where reprogramming might get us to?
It’s hard to make a guess on how far we could go with reprogramming. However I would guess we can get to at least the current maximum human lifespan of around 120 years. Maybe a few decades more. The fact that some people with exceptionally good genes have made it past 110 shows that some of the things that are never fixed, can last that long. Also the result of Harold Katcher’s experiment gives us some clues. In his experiments one of the rats given the E5 just barely broke the maximum life span for that species. The E5 is supposed to work by epigenetic reprogramming so the results are a clue that it can at least get us as far as the current maximum life span.
Using your same analogy, wiping the OS along with all the malware, spyware, and software and re-installing from scratch will probably extend the useful life of the computer. We need to do that as well as fix the physical damage by replacing the power supply, buying a new monitor, etc…
Yes definitely! I’m all in favor on pursuing reprogramming as a method to extend life. It will be super useful and necessary along with other methods. I’m only criticizing those that think that we only need reprogramming therapies to solve aging.
I don’t think the remarkable effects of OSKM can be largely explained merely by something as “simple” as increased autophagy. We don’t see autophagy inducers resulting in dedifferentiation or major rejuvenation of cells.
