Progesterone and the mTOR Aging System

Unraveling how and why we age is a research focus.  We are still captivated by the Ponce de Leon promise of the Fountain of Youth.  An enzyme system named mTOR (mammalian or mechanistic target of rapamycin) was identified in mouse studies as a significant aging mechanism.  Inhibition of mTOR by rapamycin, found in bacteria species: S. cerevisiae, C. elegans, D. melanogaster, or Mus musculus, helped identify mTOR as a central actor.

This schematic and the accompanying explanation help to illustrate the key role of mTOR. 

“Schematic representation of the role of the mTOR pathway in the regulation of hallmarks of aging (black arrows), such as nutrient availability (represented by amino acid availability), energy homeostasis, cellular senescence, cell stemness, and proteostasis. mTOR activity is regulated in part by amino acid levels, while mTOR in turn stimulates the synthesis of non-essential amino acids. The depicted hallmarks of aging are also interconnected (grey arrows), suggesting that aging is a coordinated process in which mTOR plays a significant role. mTOR, mechanistic target of rapamycin kinase.” (1)

Thus using rapamycin, which has been developed as an anticancer drug, emerged as a possible strategy by the anti-aging community.   

Dr. Ray Peat, writing in his newsletter (2,) discusses other mTOR inhibitors.  The hormone progesterone tops the list. Researchers found progesterone can bind directly to mitochondria (organelles within the cells that produce energy).   Progesterone can increase the energy production in the mitochondria as well as increase the size of the mitochondria.  Progesterone inhibits many catabolic (breaking down) processes. Including the aging caused by mTOR.

Other inhibitors include the bioflavonoid from citrus peel, nobiletin, and aspirin.

Substances that increase the aging promoted by mTOR are estrogen, radiation, the amino acids methionine and tryptophan, toxins, and lipofuscins.   The protein in gelatin is low in methionine and tryptophan and so becomes a favorable protein source. Lipofuscins are age spots caused by unsaturated fatty acids (PUFAS) and heavy metals. Reducing intake of PUFAS and exposure to heavy metals becomes an antiaging strategy.

As research continues to help unravel the mysteries of the human body, the solutions to optimizing our life span may be simple. 

(1)  Papadopoli, David et “alTOR as a central regulator of lifespan and aging”    02 Jul 2019, 8(F1000 Faculty Rev):998

(2) “Aging, Energy, Progesterone” Ray Peat’s Newsletter Q2 2022

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