Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Cell Cycle. 2022 Jul;21(14):1456-1467. doi: 10.1080/15384101.2022.2054636. Epub 2022 Mar 31.
A hallmark of cellular senescence is proliferation-like activity of growth-promoting pathways (such as mTOR and MAPK) in non-proliferating cells. When the cell cycle is arrested, these pathways convert arrest to senescence (geroconversion), rendering cells hypertrophic, beta-Gal-positive and hyperfunctional. The senescence-associated secretory phenotype (SASP) is one of the numerous hyperfunctions. Figuratively, geroconversion is a continuation of growth in non-proliferating cells. Rapamycin, a reversible inhibitor of growth, slows down mTOR-driven geroconversion. Developed two decades ago, this model had accurately predicted that rapamycin must extend life span of animals. However, the notion that senescent cells directly cause organismal aging is oversimplified. Senescent cells contribute to organismal aging but are not strictly required. Cell senescence and organismal aging can be linked indirectly via the same underlying cause, namely hyperfunctional signaling pathways such as mTOR.
细胞衰老的一个标志是促进生长的途径（如 mTOR 和 MAPK）在非增殖细胞中的增殖样活性。当细胞周期被阻断时，这些途径将阻滞转化为衰老（衰老转化），使细胞肥大、β-Gal 阳性和功能亢进。衰老相关分泌表型（SASP）是众多功能亢进之一。形象地说，衰老转化是非增殖细胞中生长的延续。雷帕霉素是一种可逆的生长抑制剂，可减缓 mTOR 驱动的衰老转化。该模型在二十年前就已经开发出来，它准确地预测了雷帕霉素必须延长动物的寿命。然而，衰老细胞直接导致机体衰老的观点过于简单化。衰老细胞会导致机体衰老，但不是必需的。细胞衰老和机体衰老可以通过相同的潜在原因间接联系起来，即 mTOR 等功能亢进的信号通路。
