Shenzhen Key Laboratory for Systemic Aging and Intervention (SKL-SAI), National Engineering Research Center for Biotechnology (Shenzhen), School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen, China.
School of Biomedical Sciences, Hunan University, Changsha, China.
Physiol Rev. 2024 Jan 1;104(1):253-280. doi: 10.1152/physrev.00044.2022. Epub 2023 Sep 7.
Aging is a chronic yet natural physiological decline of the body. Throughout life, humans are continuously exposed to a variety of exogenous and endogenous stresses, which engender various counteractive responses at the cellular, tissue, organ, as well as organismal levels. The compromised cellular and tissue functions that occur because of genetic factors or prolonged stress (or even the stress response) may accelerate aging. Over the last two decades, the sirtuin (SIRT) family of lysine deacylases has emerged as a key regulator of longevity in a variety of organisms. SIRT7, the most recently identified member of the SIRTs, maintains physiological homeostasis and provides protection against aging by functioning as a watchdog of genomic integrity, a dynamic sensor and modulator of stresses. SIRT7 decline disrupts metabolic homeostasis, accelerates aging, and increases the risk of age-related pathologies including cardiovascular and neurodegenerative diseases, pulmonary and renal disorders, inflammatory diseases, and cancer, etc. Here, we present SIRT7 as the seventh key to unlock the mystery of aging, and its specific manipulation holds great potential to ensure healthiness and longevity.
衰老是身体慢性但自然的生理衰退。在整个生命过程中，人类不断受到各种外源性和内源性应激的影响，从而在细胞、组织、器官以及机体水平上产生各种对抗性反应。由于遗传因素或长期应激（甚至应激反应）导致的细胞和组织功能受损，可能会加速衰老。在过去的二十年中，赖氨酸去乙酰化酶的 Sirtuin（SIRT）家族已成为多种生物长寿的关键调节因子。SIRT7 是 SIRTs 中最近被发现的成员，它作为基因组完整性的“看门狗”、应激的动态传感器和调节剂，维持着生理内稳态并提供对衰老的保护。SIRT7 的下降会破坏代谢内稳态，加速衰老，并增加与年龄相关的病理学的风险，包括心血管和神经退行性疾病、肺部和肾脏疾病、炎症性疾病和癌症等。在这里，我们将 SIRT7 作为揭示衰老之谜的第七把钥匙，并认为对其进行特定的操作具有确保健康和长寿的巨大潜力。
