ORRAPA
#1
Senescent cell turnover slows with age providing an explanation for the Gompertz law
https://www.nature.com/articles/s41467-019-13192-4
According to this article much of aging (in mice) can be split between two factors. The first how how quickly senescent cells build up. This increases linearly with age. The second is how many senescent cells are already around, as they inhibit their own removal.
So how do current longevity treatments interact with this model.
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#3
@John_Hemming what do you think about this?
I think there are two main drivers, mitochondrial failure (low MMP) and senescence. If you consider the citrate supplementation experimentation with drosophila you see the lifespan curve move moreso towards a pure Gompertz style curve. I think that is because it is moving to be primarily mitochondrial.
The maths of this I think will derive from approaches similar to Drenick’s failure law
https://epubs.siam.org/doi/10.1137/0108051
Someone else’s summary:
The exponential distribution is inadequate as a failure time model for most components; however, under certain conditions (in particular, that component failure rates are small and mutually independent, and failed components are immediately replaced or perfectly repaired), it is applicable to complex repairable systems with large numbers of components in series, regardless of component distributions, as shown by Drenick in 1960. This result implies that system behavior may become simpler as more components are added. We review necessary conditions for the result and present some simulation studies to assess how well it holds in systems with finite numbers of components. Lastly, we also note that Drenick’s result is analogous to similar results in other systems disciplines, again resulting in simpler behavior as the number of entities in the system increases.
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