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.