Friday, February 28, 2020

Joe Rogan Experience #1432 - Aubrey de Grey





Comment: My problem with Aubrey is that he thinks solving aging is an engineering issue. But I think when handling the high metabolism nondividing neurons design, nature essentially solved aging at the cellular level. A mouse neuron transplanted to a rat lives twice as long as a mouse, just as long as a rat, and could potentially live even longer in an even longer lived species.
After essentially having a solution to aging baked in, nature had to adjust organism lifespan to their niche.
Michael Fossel, iirc, claims that many of the maintenance mechanisms are downregulated in an age related manner. And it is this downregulation of maintenance that leads to all the issues we see.
It was discovered that the rate of telomere shortening predicts species lifespan.
Researchers discover that the rate of telomere shortening predicts species lifespan. A flamingo lives 40 years and a human being lives 90 years; a mouse lives two years and an elephant lives 60.J What counts is not their length, but the rate at which they shorten | A better predictor than body size or heart rate https://phys.org/news/2019-07-telomere-shortening-species-lifespan.html
Would telomere lengthening work against aging? Maybe it wouldn't solve everything, but such therapies sound highly promising.
I think Aubrey's ideas might work but they seem like overengineering. We have seen that we had a mammal ancestor with mice like lifespan to reach our human lifespan nature did not need to transfer more genes from the mitochondria to the nucleus, nor did it abolish telomeres, etc. Even longer lived mammals, iirc, have not transfered additional mito genes to the nucleus.
We know there are superagers with brain functioning akin to 20 year olds. The brain functions at ultra high metabolism for decades, but when aging affects the support system and garbage clearance mechanisms, issues start to arise.
I think just like glymphatic systems helps transport garbage out of the brain, the lymphatic system does similar across the body. But aging compromises it too.
edit: Regards the idea that there's a trade off between cancer and aging. Mice engineered to have extra long telomeres had extended lifespan and did not have additional cancer rates.
Importantly, mice with hyper-long telomeres show an increased longevity and develop less tumors associated with aging. Together, these findings demonstrate that longer telomeres than normal show beneficial effects in mice, delaying metabolic aging and cancer, and resulting in longer lifespans. https://www.nature.com/articles/s41467-019-12664-x
edit2:There's also the fact that some mice appear cancer immune and a fraction of the human population might as well be( lifelong heavy smoker centenarians for example.). I think the additional copies of anticancer genes in extremely large animals are to protect against cancer during embryonic development, but theoretically the immune system might be sufficient at least in a fraction of the population.
IMHO, it is likely the body already has the capability for significantly longer lifespan. Rather than look for trying to redesign fundamental biological components past what nature has done, I think, in the short term, the search for small molecules that can restore epigenetic age and telomere length sounds more promising.

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