Cryandian

Biologist

[Cryandian @cryandian]

@davidasinclair Wrong! New fixed mutations are acquired after each stem cell division.

[Cryandian @cryandian]

@CraigBrockie No! It is the result of mutation accumulation in hair follicle stem cells. These cells become senescent to protect from hair follicle cancer, resulting in graying.

[Cryandian @cryandian]

@LidskyPeter This is actually from a nature article. I will find it and send it. But right now I’m in Gøteborg with my family and about to eat do I’ll get back to you😊

[Cryandian @cryandian]

The naked mole rat can reach 30 years of age. Slow aging and cancer resistant bats can live up to 50 years. If the elephant were to age at the same as these species they would live to be 600 + years. They cannot do so because they have to age to fight cancer (which they do extremely well).

[Cryandian @cryandian]

@LidskyPeter No mutations are not preventable, but natural selection has clearly favored enhanced genome maintenance in some species. This is especially true for species with extended parental care.

[Cryandian @cryandian]

Yes it does, let me again use the elephant as an example. Elephants, with their multiple copies of TP53 (up to 19–20 retrogene copies compared to humans’ single copy), exhibit enhanced p53-mediated DNA damage response, leading to higher rates of apoptosis or cell cycle arrest in response to DNA damage. This results in low cancer rates despite their large body size and long lifespan, as it reduces the accumulation of deleterious mutations. However, this comes at the cost of accelerated aging relative to their body size, as the increased cell turnover and removal deplete stem cell pools or impair tissue homeostasis over time, leading to faster phenotypic aging (e.g., tissue degeneration, reduced regenerative capacity).

[Cryandian @cryandian]

@LidskyPeter Species with low risk of cancer already have low risk of passing on deleterious cells to their progeny, which allows for a slower rate of aging.

[Cryandian @cryandian]

@LidskyPeter No, this not correct. For example with constitutively activation of p53 cells are removed at a higher rate from the tissue (lower tolerance for DNA-damage) . This reduces the risk of cells passing on deleterious mutations to daughter cells, but at cost of accelerated aging.

[Cryandian @cryandian]

@LidskyPeter So if I correct, all very slow aging species will be highly cancer resistant and maintain high NAD/NADH ration, high SIRT activity.

[Cryandian @cryandian]

@LidskyPeter These species age slower because of their low risk of cancer.

[Cryandian @cryandian]

@LidskyPeter The main reason is that somatic mutations are irreversible.

[Cryandian @cryandian]

Well this is connected to their life history strategies. For example Humans, elephants, whales that have extended parental care have evolved higher efficiency in genome maintenance to be able to live long enough to not only raise their young, but to contribute in raising their grandchildren. Since mutations are unavoidable and irreversible we have to age to avoid cancer at an age where we would still be under influenced by the force underlying natural selection.

[Cryandian @cryandian]

@LidskyPeter And once fixed in the genome they are for ever invisible to DNA-repair pathways.

[Cryandian @cryandian]

@LidskyPeter Because mutations are 100% unavoidable due to evolutionary constraints in DNA-repair and proofreading mechanisms.

[Cryandian @cryandian]

@LidskyPeter So my model is very simple.