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Poster Presentations
Day 4, June 25（Wed.）
Room P (Maesato East, Foyer, Ocean Wing)
- 4P-PM-22
Branched-Chain Amino Acid Metabolism as a Crucial Modulator of Cellular Senescence
(Gunma Univ)
oHideru Obinata, Kazuki Irie, Yuma Aramaki, Junki Hoshino, Yoji Minamishima, Akimitsu Konishi
Aging is a process of losing the ability to maintain homeostasis in multiple tissues. This inability is attributed mostly to the accumulated senescent cells, a state of irreversible cell cycle arrest by various cellular stress. Although there are growing lines of evidence that various metabolic changes occur in senescent cells, the link between cellular metabolism and senescence is not yet fully understood.
We conducted metabolomic analysis both in aged mice and senescent cells and found that the branched-chain amino acids (BCAAs) levels were commonly altered. BCAAs were increased in the plasma from aged mice as well as in the cells in which premature cellular senescence was induced by various stress such as X-ray irradiation and telomere shortening. Further analyses revealed that premature cellular senescence reduced the expression of BCAA aminotransferase 2, thus resulted in decreased catabolism of BCAAs and reduced synthesis of glutamate. The reduction of BCAA catabolites, together with the consequent limitation in glutathione production, triggered cellular senescence. Furthermore, a reduction of BCAT2 levels alone was sufficient to induce cellular senescence, both in cultured cells and in mice. Our findings provide new insights into the metabolic mechanisms underlying cellular senescence, with a particular focus on the role of BCAAs.