Geriatric unit, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Geriatr Gerontol Int. 2021 Feb;21(2):125-130. doi: 10.1111/ggi.14121. Epub 2020 Dec 28.
Historically, the findings from cellular lifespan studies have greatly affected aging research. The discovery of replicative senescence by Hayflick developed into research on telomeres and telomerase, while stress-induced senescence became known as a telomere-independent event. Senescence-inducing signals comprise several tumor suppressors or cell cycle inhibitors, e.g., p53, cyclin-dependent kinase inhibitor p16 Ink4a and others. Stress-induced senescence serves as a physiological barrier to oncogenesis in vivo, while it activates senescence-associated secretary phenotype, inducing chronic inflammation. Thus, beside telomere length, p16, p53 and inflammatory cytokines have been utilized as biomarkers for cellular senescence. Telomere lengths in human leukocytes correlate well with events of aging-related lifestyle diseases, indicating the importance of cellular senescence in organismal aging. As such, the development of senescence research will have significant future clinical applications, e.g., senolysis. Geriatr Gerontol Int 2021; 21: 125-130.
从历史上看，细胞寿命研究的发现极大地影响了衰老研究。Hayflick 发现的复制性衰老发展成为端粒和端粒酶的研究，而应激诱导的衰老则被认为是一种与端粒无关的事件。诱导衰老的信号包括几种肿瘤抑制因子或细胞周期抑制剂，例如 p53、细胞周期蛋白依赖性激酶抑制剂 p16 Ink4a 等。应激诱导的衰老作为体内致癌的生理屏障，同时激活衰老相关分泌表型，诱导慢性炎症。因此，除了端粒长度外，p16、p53 和炎性细胞因子已被用作细胞衰老的生物标志物。人类白细胞中的端粒长度与与衰老相关的生活方式疾病的发生密切相关，这表明细胞衰老在机体衰老中的重要性。因此，衰老研究的发展将具有重要的未来临床应用，例如衰老细胞清除。《老年医学与老年病学国际杂志》2021;21:125-130。
