Sirt1, also known as silent information regulator sirtuin 1 and silencing information regulator 2 related enzyme 1, is an NAD+-dependent deacetylase belonging to the sirtuin family. It post-translationally modulates various biological processes by deacetylating histones and non-histone proteins. Sirt1 is involved in pathways related to inflammation, aging, mitochondrial function, autophagy, and immune responses, which are crucial for maintaining cellular homeostasis and organismal health. Genetic models, especially KO/CKO mouse models, are valuable for studying Sirt1's functions in vivo [1,2,3,4,5,6].

In aging-related studies, Sirt1 expression declines with aging in mice, and increased Sirt1 expression can extend lifespan in yeast, C. elegans, and mice, indicating its role in regulating cellular senescence and aging [2]. In autoimmune diseases, Sirt1 regulates inflammation, oxidative stress, and immune responses, and its altered functions may be involved in the pathogenesis of these diseases. Inhibitors and activators of Sirt1 can affect the development of autoimmune diseases, suggesting it as a potential therapeutic target [4]. In myocardial ischemia-reperfusion injury, Sirt1 regulates autophagy, which is a double-edged sword in this injury. Sirt1-mediated autophagy plays different roles at different stages of myocardial I/R injury, and targeting this mechanism can lead to the development of new drugs [5].

In conclusion, Sirt1 is a multifunctional enzyme essential for regulating numerous biological processes. Studies using KO/CKO mouse models have revealed its significant roles in aging-related diseases, autoimmune diseases, and myocardial ischemia-reperfusion injury. Understanding Sirt1's functions provides potential therapeutic strategies for these disease areas.

References:

1. Yang, Yunshu, Liu, Yang, Wang, Yunwei, Tie, Jun, Hu, Dahai. 2022. Regulation of SIRT1 and Its Roles in Inflammation. In Frontiers in immunology, 13, 831168. doi:10.3389/fimmu.2022.831168. https://pubmed.ncbi.nlm.nih.gov/35359990/

2. Chen, Cui, Zhou, Min, Ge, Yuchen, Wang, Xiaobo. 2020. SIRT1 and aging related signaling pathways. In Mechanisms of ageing and development, 187, 111215. doi:10.1016/j.mad.2020.111215. https://pubmed.ncbi.nlm.nih.gov/32084459/

3. Tang, Bor Luen. 2016. Sirt1 and the Mitochondria. In Molecules and cells, 39, 87-95. doi:10.14348/molcells.2016.2318. https://pubmed.ncbi.nlm.nih.gov/26831453/

4. Shen, Pan, Deng, Xuan, Chen, Zhe, Yan, Jiahui, Tu, Shenghao. 2021. SIRT1: A Potential Therapeutic Target in Autoimmune Diseases. In Frontiers in immunology, 12, 779177. doi:10.3389/fimmu.2021.779177. https://pubmed.ncbi.nlm.nih.gov/34887866/

5. Ding, Xiaoqing, Zhu, Chenyu, Wang, Wenhong, Ma, Chunwei, Gao, Binghong. 2023. SIRT1 is a regulator of autophagy: Implications for the progression and treatment of myocardial ischemia-reperfusion. In Pharmacological research, 199, 106957. doi:10.1016/j.phrs.2023.106957. https://pubmed.ncbi.nlm.nih.gov/37820856/

6. Kim, Ji Yong, Mondaca-Ruff, David, Singh, Sandeep, Wang, Yu. 2022. SIRT1 and Autophagy: Implications in Endocrine Disorders. In Frontiers in endocrinology, 13, 930919. doi:10.3389/fendo.2022.930919. https://pubmed.ncbi.nlm.nih.gov/35909524/