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Autophagy: The “self-digestion” longevity pathway

Autophagy is the natural, regulated mechanism of the cell that responds to senescence through the removal of unnecessary or dysfunctional cells, aka Zombie cells, and their cellular components. One of the best known and studied inducers of autophagy is dietary fasting. Autophagy allows the orderly degradation and recycling of senescent cellular components.

Autophagy: The “self-digestion” longevity pathway

Dysregulation or inhibition of autophagy processes have been linked to diabetes, cardiovascular disease, neurodegenerative diseases, Parkinson’s disease, and cancer.

Autophagy is the major degradation pathway in almost all eukaryotic cells and is essential for the removal of damaged organelles from the cytoplasm. Thus, autophagy is a way for the cell to recycle old and damaged materials by breaking them down into their smaller components, allowing for their reuse and resynthesis into newer and healthier cellular structures.

This is important to understand because when nutrients are over-abundant, as in the standard American diet, or SAD Diet, the ubiquitous survival protein mTORC1 will inhibit autophagy and promote over function. mTORC1’s ability to inhibit autophagy while at the same time stimulate protein synthesis and cell growth can result in accumulations of damaged proteins and organelles, contributing to damage at the cellular level.

Thus over expression of mTORC leads to dysregulation and inhibition of autophagy processes, and this is strongly linked to diabetes, cardiovascular disease, cancer, and neurodegenerative diseases, including Parkinson’s disease and Alzheimer’s disease.

mTORC1 inhibition in turn activates autophagy and starts a quality control program that removes damaged lysosomes, referred to as lysophagy. Chaperone mediated autophagy is when dysfunctional senescent cells are immunologically tagged for recycling of their cell components by autophagosomes.

Because autophagy appears to decline with age, activation of autophagy may help promote longevity in humans. The brain is particularly reliant on autophagy, and in fact, inactivating autophagy in mammals leads to rapid death from fatal neurodegenerative collapse.

Related references:

Mikhail V. Blagosklonny. From rapalogs to anti-aging formula. Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA Oncotarget, 2017, Vol. 8, (No. 22), pp: 35492-35507