Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University, Guilin 541100, China.
The Fifth Affiliated Hospital of Southern Medical University, Guangzhou 510900, China.
Acta Biochim Biophys Sin (Shanghai). 2023 Jul 3;55(8):1168-1183. doi: 10.3724/abbs.2023107.
Cellular senescence is a state of irreversible cellular growth arrest that occurs in response to various stresses. In addition to exiting the cell cycle, senescent cells undergo many phenotypic alterations, including metabolic reprogramming, chromatin rearrangement, and senescence-associated secretory phenotype (SASP) development. Furthermore, senescent cells can affect most physiological and pathological processes, such as physiological development; tissue homeostasis; tumour regression; and age-associated disease progression, including diabetes, atherosclerosis, Alzheimer's disease, and hypertension. Although corresponding anti-senescence therapies are actively being explored for the treatment of age-associated diseases, the specific regulatory mechanisms of senescence remain unclear. N -methyladenosine (m A), a chemical modification commonly distributed in eukaryotic RNA, plays an important role in biological processes such as translation, shearing, and RNA transcription. Numerous studies have shown that m A plays an important regulatory role in cellular senescence and aging-related disease. In this review, we systematically summarize the role of m A modifications in cellular senescence with regard to oxidative stress, DNA damage, telomere alterations, and SASP development. Additionally, diabetes, atherosclerosis, and Alzheimer's disease regulation via m A-mediated cellular senescence is discussed. We further discuss the challenges and prospects of m A in cellular senescence and age-associated diseases with the aim of providing rational strategies for the treatment of these age-associated diseases.
细胞衰老（Cellular senescence）是一种细胞在受到各种压力后不可逆的生长停滞状态。除了退出细胞周期外，衰老细胞还会经历许多表型改变，包括代谢重编程、染色质重排和衰老相关分泌表型（SASP）的发展。此外，衰老细胞可以影响大多数生理和病理过程，如生理发育、组织稳态、肿瘤消退以及与年龄相关的疾病进展，包括糖尿病、动脉粥样硬化、阿尔茨海默病和高血压。尽管针对与年龄相关的疾病的抗衰老治疗正在积极探索，但衰老的具体调节机制仍不清楚。N6 -甲基腺苷（m A）是一种普遍存在于真核 RNA 中的化学修饰，在翻译、剪切和 RNA 转录等生物学过程中发挥着重要作用。大量研究表明，m A 在细胞衰老和与衰老相关的疾病中起着重要的调节作用。在这篇综述中，我们系统地总结了 m A 修饰在氧化应激、DNA 损伤、端粒改变和 SASP 发展等方面对细胞衰老的作用。此外，还讨论了 m A 介导的细胞衰老对糖尿病、动脉粥样硬化和阿尔茨海默病的调节作用。我们进一步讨论了 m A 在细胞衰老和与年龄相关的疾病中的挑战和前景，旨在为这些与年龄相关的疾病的治疗提供合理的策略。
