Glutamine Supplementation in Old Age May Produce Similar Effects to mTOR Inhibition
Researchers here link lower levels of glutamine with rising activation of mTOR signaling in aging, showing that it increases the burden of cellular senescence and impairs the cellular maintenance processes of autophagy. Either glutamine supplementation or mTOR inhibition addresses these specific defects. This is an interesting addition to what is known of the role of mTOR in aging, an area of active interest, with numerous mTOR inhibitor small molecule drugs presently under development. If the less costly and more readily available approach of glutamine supplementation can produce much the same benefits, that is a promising development.
Glutamine is a conditionally essential amino acid involved in energy production and redox homeostasis. Aging is commonly characterized by energy generation reduction and redox homeostasis dysfunction. Various aging-related diseases have been reported to be accompanied by glutamine exhaustion. Glutamine supplementation has been used as a nutritional therapy for patients and the elderly, although the mechanism by which glutamine availability affects aging remains elusive.
Here, we show that chronic glutamine deprivation induces senescence in fibroblasts and aging in Drosophila melanogaster, while glutamine supplementation protects against oxidative stress-induced cellular senescence and rescues the D-galactose-prompted progeria phenotype in mice. Intriguingly, we found that long-term glutamine deprivation activates the Akt-mTOR pathway, together with the suppression of function. However, the inhibition of the Akt-mTOR pathway effectively rescued the autophagy impairment and cellular senescence caused by glutamine deprivation.
Collectively, our study demonstrates a novel interplay between glutamine availability and the aging process. Mechanistically, long-term glutamine deprivation could evoke mammalian target of rapamycin (mTOR) pathway activation and autophagy impairment. These findings provide new insights into the connection between glutamine availability and the aging process.
So confusing. You have this study positive on Glutamine - it inhibits mtor
then you have this one that's so negative
" A study in mice suggests that glutamine prevents senescent cells from being cleared, which promotes aging"
https://medium.com/predict/suppressing-glutamine-metabolism-to-slow-aging-2154e6f3b485
Can somebody make sense of this paradox?
At August, I personally don't even read any study done in China unless it is published in a very high impact journal
Here is the actual study
https://www.natap.org/2021/HIV/265.full.pdf
" Elimination of SnCs and protection from senescence by inhibition of glutaminolysis in the aged body may ameliorate tissue microinflammation, prevent age-associated disorders, and even extend life span and rejuvenate an aging individual."
Here is a study shown on fightaging suggesting that blocking the enzyme responsible for glutamine production kills scenecent cells.
My question: To take glutamine as a supplement or not?
"GLS1) is a mitochondrial enzyme found in endothelial cells (ECs) that metabolizes glutamine to glutamate"
https://www.fightaging.org/archives/2021/02/inhibition-of-gls1-selectively-destroys-senescent-cells/#comments
another :
" Glutamine metabolism is one of the hallmarks of cancers which is described as an essential role in serving as a major energy and building blocks supply to cell proliferation in cancer cells. Many malignant tumor cells always display glutamine addiction. "
https://link.springer.com/article/10.1007/s12094-021-02645-2
So here we are in 2024 and still no one has taken a stab at solving this Glutamine paradox. I was just about to order more of this until I read these comments. Now I don't know. If anyone has done any more reseach on this and has new info please enlighten us. and Thanks!