Could the age-related decline in autophagy be partly to blame for the increased cellular senescence and accumulation of lipofuscin with age?
Autophagy is the clearing out of old, senescent cells to make room for newer, younger cells. The research group in this paper found that markers of autophagy declined during aging in rats.
This research group administered blood plasma from young rats into older rats and found autophagy in the old rats was enhanced. Remarkably, lipofuscin deposits in the liver were reduced, and the liver was protected from cellular senescence. Both positive effects were prevented if the enhanced autophagy was inhibited.
These results suggest that the accumulation of both lipofuscin and senescent cells might not be simple byproducts of the daily metabolism that keeps us alive. Lipofuscin accumulation and cellular senescence may occur partly because cellular cleanup and recycling processes—autophagy—ceases to work properly in advancing age. This is consistent with some other findings: other interventions that enhance autophagy, such as calorie restriction, fasting, and rapamycin, are also known to be positive for healthspan and longevity, if administered in the optimal doses.
These young plasma transfer experiments were done in rats, so it’s important to consider whether the same things happen in aging humans. And another question to consider is: why does autophagy decline during aging? Is there something we can do to keep it functioning at youthful levels indefinitely?
At the Methuselah Foundation, we are opposed to transfusion-based rejuvenation therapies. The ethical implications of these procedures compelled us to seek superior alternatives. Our proposed approach to a potential application of this knowledge is not to rejuvenate blood but rather to rejuvenate where the blood is produced: the bone marrow. This would provide an elegant systemic solution where young marrow would produce young blood without the need of a transfusion.