基盤セッション
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1A-O-1112 PDF
細胞老化過程における分岐鎖アミノ酸代謝の変調
Aging is a process of reducing 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 such as DNA damage, oncogene activation, replicative stress and telomere shortening. Although the pieces of evidence of metabolic alterations in senescent cells have been piled up, the causes and consequences of cellular metabolic changes on cellular senescence are largely unknown.
We conducted metabolomic analysis in aged mice and senescent cells and found that the levels of branched-chain amino acids (BCAAs) 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 BCAA catabolic flow. Reduction of BCAA transamination alone was sufficient to induce cellular senescence, while improved BCAA catabolic flow inhibited replicative senescence mimicked by telomere shortening. Our findings identify novel metabolic contributions of BCAAs to cellular senescence.