Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
Department of Genetics, Graduate School of Pharmaceutical Science, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-0033, Japan.
Sci Rep. 2022 Apr 4;12(1):5593. doi: 10.1038/s41598-022-09424-1.
Tissue aging is a major cause of aging-related disabilities and a shortened life span. Understanding how tissue aging progresses and identifying the factors underlying tissue aging are crucial; however, the mechanism of tissue aging is not fully understood. Here we show that the biosynthesis of S-adenosyl-methionine (SAM), the major cellular donor of methyl group for methylation modifications, potently accelerates the aging-related defects during Drosophila oogenesis. An aging-related increase in the SAM-synthetase (Sam-S) levels in the germline leads to an increase in ovarian SAM levels. Sam-S-dependent biosynthesis of SAM controls aging-related defects in oogenesis through two mechanisms, decreasing the ability to maintain germline stem cells and accelerating the improper formation of egg chambers. Aging-related increases in SAM commonly occur in mouse reproductive tissue and the brain. Therefore, our results raise the possibility suggesting that SAM is the factor related to tissue aging beyond the species and tissues.
组织衰老（tissue aging）是与衰老相关的残疾和寿命缩短的主要原因。了解组织衰老的进展以及确定组织衰老的根本原因至关重要；然而，组织衰老的机制尚未完全阐明。在这里，我们发现 S-腺苷甲硫氨酸（SAM）的生物合成，即甲基化修饰的主要细胞供体甲基供体，有力地加速了果蝇卵子发生过程中的与衰老相关的缺陷。生殖系中 SAM 合酶（Sam-S）水平的与衰老相关的增加导致卵巢 SAM 水平的增加。SAM 依赖性 SAM 的生物合成通过两种机制控制卵子发生过程中的与衰老相关的缺陷，即降低维持生殖干细胞的能力和加速卵囊的不当形成。SAM 与衰老相关的增加通常发生在小鼠生殖组织和大脑中。因此，我们的研究结果表明 SAM 是超越物种和组织的与组织衰老相关的因素。
