Here’s a really interesting paper from Steve Horvath. This aligns with my theory that our maximum lifespan is hardwired and it’s going to be very challenging to break the limit.
I’m excited by the treatments that are going to hopefully be available soon, but at most we’ll be able to restore a person to their maximum lifespan and not beyond. I don’t think repair is going to be enough.
Most likely the only way we’re going to reach longevity escape velocity is by bioengineering more resilience.
It probably won’t change without any intervention, but it can be reversed with gene therapy, namely Yamanaka factors. With rapamycin, you can maybe get close to the maximum programmed lifespan, but yes, rapamycin may not change the ceiling limit. I think the ceiling lifespan for humans is around 150. The article didn’t mention rapamycin.
I do not see anything in this paper that supports your pessimistic conclusion, on the contrary, there are numerous points where we can be rather optimistic in our interpretation. It is a regression based predictor of natural lifetimes, quite to be expected and little to do with what could be technically (unnaturaly) achieved. Moreover, it fails to predict the much longer lifetime of small dogs, so large Danes might hope to get to those with some trick. Or, for another example, they do predict age of sexual maturity, and yet we know how to stop puperty and let a human never mature. So let us find the trick to never die.
Actually the paper does address it, the epigenetic predictor couldn’t differentiate between dog breeds lifespan’s effectively. The methylation pattern mirrored the wolf, rather than variations created by selective breeding.
The variance in dog age has more to do with higher metabolic demand in larger dogs and increased growth rate- that’s why bigger humans tend to live slightly shorter than smaller people.
But the paper is saying is that all these variations occur within the species limit.
I’d like to point out that I didn’t say we definitely won’t cure aging, I just believe that repair isn’t going to be enough.
I think that only way to break maximal lifespan will be to engineer a more resilient organism, which is going to be extremely challenging- however challenging doesn’t mean impossible.
My feeling is that on an organismal level humans simple aren’t robust enough, we have a limited allostatic load.
But there’s lots to be excited about, nanotechnology might be able to improve cell resilience. Gene therapy like adding an additional Sirt 6 gene, and looking at ways to engineer human immunity to be more like bat immune systems might help us break the barrier.
Steve Horvath mentioned that partial reprogramming didn’t have any effect on maximal lifespan, but it might be that it’s just not effective enough to fully change the epigenome.
I did not say that the paper did not address certain issues, I say that your interpretation of what it means for advancing human lifespan is not anywhere supported in the paper. The dogs and wolves issue alone shows that the epigenetic regression prediction of natural maximum lifespan is useless for any particular breed, and this without even doing anything unnatural like feeding them rapamycine.
Just look at age of sexual maturity. Your interpretation is that humans can never delay it indefinitely just because one can predict natural limits?? Got news for you: Puperty blockers!
sure your point about genetic interventions affecting biological processes is valid. Though I think Kallmann syndrome is an interesting example that tests this - it completely prevents puberty, a major developmental process, yet doesn’t extend lifespan, which suggests that while we can modify biological timing (as you note with puberty blockers), this doesn’t necessarily alter the fundamental species limits the methylation patterns seem to show.
I recommend to work hard on first understanding what a text, whether paper or here a commenter, actually sais, the logic of the argument, why did I mention the age of sexual maturity for example.
I did not at all make the point you say I made.
People usually jump to the conclusion that these kinds of correlations between aging and epigenetic signatures mean that the epigenetics are causing aging. They don’t usually consider the alternative, which is that aging causes the epigenetics signature to become old. Correlation doesn’t always mean causation. Personally I think it’s both ways. Epigenetic changes cause some parts of aging (a lot is not caused by epigenetic changes), but aging also causes epigenetic changes.
I think this is basically true. I think the methylation changes indicate which genes are not being transcribed much like grass that grows on a road which has little traffic. Hence as the creature gets older some genes stop being transcribed.
The reason for the change in gene expression is the combination of a reduction in the power level of the cell (total from all mitochondria in the cell) and the presence of senescent cells creating SASP. (which inhibits SLC25A1)
I think the main thing that scientists interested in longevity should focus on is DNA methylation patterns. The ceiling limit of life is related to these hypermethylation and hypomethylation regions. If these methylation patterns are solved with an artificial intelligence-based program, that is, if it is known which genes are silenced by hypo or hypermethylation and which ones are made more active, the problem will be over. The rest can be done with crispr c9 enzymes.