Garmendia-Berges Maider, Sola-Sevilla Noemi, Mera-Delgado MCarmen, Puerta Elena
Pharmaceutical Sciences Department, Division of Pharmacology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain.
Biology (Basel). 2023 Nov 29;12(12):1476. doi: 10.3390/biology12121476.
Sirtuin 2 (SIRT2), one of the seven members of the sirtuin family, has emerged as a potential regulator of aging and age-related pathologies since several studies have demonstrated that it shows age-related changes in humans and different animal models. A detailed analysis of the relevant works published to date addressing this topic shows that the changes that occur in SIRT2 with aging seem to be opposite in the brain and in the periphery. On the one hand, aging induces an increase in SIRT2 levels in the brain, which supports the notion that its pharmacological inhibition is beneficial in different neurodegenerative diseases. However, on the other hand, in the periphery, SIRT2 levels are reduced with aging while keeping its expression is protective against age-related peripheral inflammation, insulin resistance, and cardiovascular diseases. Thus, systemic administration of any known modulator of this enzyme would have conflicting outcomes. This review summarizes the currently available information on changes in SIRT2 expression in aging and the underlying mechanisms affected, with the aim of providing evidence to determine whether its pharmacological modulation could be an effective and safe pharmacological strategy for the treatment of age-related diseases.
沉默调节蛋白2（SIRT2）是沉默调节蛋白家族七个成员之一，由于多项研究表明其在人类和不同动物模型中呈现与年龄相关的变化，它已成为衰老及与年龄相关疾病的潜在调节因子。对迄今发表的关于该主题的相关研究进行详细分析表明，SIRT2随衰老发生的变化在大脑和外周似乎是相反的。一方面，衰老会导致大脑中SIRT2水平升高，这支持了其药理学抑制在不同神经退行性疾病中有益的观点。然而，另一方面，在外周，SIRT2水平随衰老而降低，而维持其表达可预防与年龄相关的外周炎症、胰岛素抵抗和心血管疾病。因此，全身性给予该酶的任何已知调节剂都会产生相互矛盾的结果。本综述总结了目前关于衰老过程中SIRT2表达变化及其潜在影响机制的可用信息，旨在提供证据以确定其药理学调节是否可能成为治疗与年龄相关疾病的有效且安全的药理学策略。
