Karl R. Pfleger’s Post

Aubrey de Grey & Peter Fedichev debated whether rejuvenation (reversal of biological age) is possible or not, 2024/5/27 https://lnkd.in/gasHcMhB My summary, personal take, & 3 suggested topics for further discussion: Background Peter published papers reportedly showing rejuvenation to be impossible. Aubrey's plan to defeat aging is well known to be a rejuvenation plan. The discussion made clear that they agree on many things & helpfully clarified Peter's position. Summary of the most important stuff: Both unashamedly say extreme progress vs aging is their goal, not only small healthspan extension or squaring the curve. Aubrey did not prove that rejuvenation is possible nor did Peter prove that it is impossible. Peter distinguishes 2 kinds of molecular damage that need to be reversed for rejuvenation: (A) Non-random damage that increases exponentially w/ aging & has strong correlations eg across cells/tissues/organs. This includes most well-known damage types that Aubrey & SENS typically discuss, eg senescent cells, lipofuscin, AGE crosslinks, etc. (B) Uncorrelated random damage that accumulates linearly, eg DNA mutations & epi-mutations, but not only these. He called this "configurational entropy" in analogy with a physics concept. Repairing this damage type requires undoing each individual change in each place (eg each cell) which is harder because each cell's random changes differ, so there's no simple enzyme or therapy for performing the same molecular change everywhere. The crux of Peter's pessimism about rejuvenation is that restoring every part of the body to its pristine pre-random-changes state is too hard. Aubrey thinks that epigenetic reprogramming (eg OSKM) strongly hints that this problem can be solved. Their overall positions are not as far apart as the hype & coverage of Peter's earlier papers suggest. Peter admits that biology is physics & the ability to manipulate molecules well enough in some distant future will enable full rejuvenation. His claim of impossibility refers specifically to a very short time scale of near future (he said initially 5 years, plus 10yrs for testing before availability). IIRC, he admitted that 100+ years is hard to predict, so the pessimism seems to be limited to achieving reversal of this type of damage within somewhere between 5 & 100 years, but that's enough for Peter to think that less effort should be devoted to damage repair & more to radically slowing aging. Aubrey thinks full damage repair is possible soon enough that it should have a big concerted effort behind it (as he has long advocated), so not only not be abandoned but should get increasing resources. Aubrey however admits that it's largely unknown how quickly certain levels of effectiveness can be achieved with this approach. Both in fact admit large levels of uncertainty with many remaining empirical unknowns & seem happy to have further conversations. My personal take & 3 suggested topics for further discussion in comments...