[ExI] Autophagy and Aging
avant at sollegro.com
Sun May 5 11:55:06 UTC 2019
Rafal Smigrodzki wrote:
> Regarding the role of autophagy - this is indeed a crucial
> maintenance process which becomes suppressed by the continuous ad
> lib feeding typical of modern lifestyles. Humans have not evolved
> under conditions of continuous food availability and our metabolism
> is not adapted to it.
Agreed. Many paleo diet practitioners put too much emphasis on eating
what early humans ate, completely ignoring the timing of how often
they ate it.
> However, I doubt that recycling of proteins is really what matters
> in autophagy - my guess is that the real mechanism responsible for
> aging retardation by fasting is actually mitophagy, or the disposal
> of mitochondria. This process selectively removes metabolically
> defective mitochondria and their mutated genomes that are
> responsible for metabolic defects, thus slowing down the long-term
> accumulation of mitochondrial mutations, which is one of the key
> mediators of aging.
Well in the cases of age-related diseases like Alzheimer's, where
damaged proteins (beta-amyloid plaques) are implicated, the benefit of
protein recycling is pretty cut and dry. But the selective removal of
defective mitochodria is certainly no less important and could very
well be the primary anti-aging mechanism.
Fasting and autophagy have many complex downstream effects including
cross-talk with apoptotic signalling pathways involved in tumor
supression. Mitochondria and mitophagy might very well be one of the
mediators of that cross-talk between the autophagic and apoptotic
"Autophagy increases the threshold of stress required for the
induction of cell death by several mechanisms. These include the
selective removal of damaged, potentially apoptosis-inducing
mitochondria or that of other potentially lethal organelles, such as
damaged zymogen granules in the exocrine pancreas. Autophagy can also
lead to the selective elimination of pro-apoptotic signal transducers."
That passage suggests that autophagy is an attempt to directly prolong
the life of individual cells by removing and replacing damaged
components including mitochondria.
More information about the extropy-chat