Thread by @Mangan150

Aging is characterized by decline in autophagy, the cellular self-cleansing process that eliminates junk molecules.

Why does this happen?

Accumulation of lipofuscin - age pigment - which is insoluble, essentially gumming up the machinery. febs.onlinelibrary.wiley.com/doi/full/10.10…

Eventually this leads to the "garbage catastrophe of aging", in which cells do not function properly. tandfonline.com/doi/abs/10.117…

Increased autophagy is essential for extension of lifespan and healthspan.

Decreasing lipofuscin could prevent this.

Eliminating lipofuscin rejuvenates cells.

jci.org/articles/view/…

Lipofuscin is composed of oxidized proteins, lipids, and iron.

Iron is a crucial ingredient that does the oxidizing, and comes from the breakdown of iron-containing proteins.

The lipids are largely polyunsaturated.

europepmc.org/article/med/70…

Polyunsaturated fats are the main component of seed oils, and readily react with iron to form lipofuscin.

Logically, lower consumption of seed oils would reduce the amount of lipofuscin.

Lower body iron stores would reduce the amount of reactive iron in lysosomes.

Higher consumption of seed oils, as well as excess body iron stores, could accelerate aging.

Decreased autophagy leads to accumulation of dysfunctional mitochondria.

Rapamycin, a drug that extends lifespan and healthspan in animals, removes lipofuscin by increasing autophagic flux.

This mechanism may be the main way it extends lifespan.
sciencedirect.com/science/articl…