ABSTRACT Sirtuin 1 (SIRT1) is a NAD + ‐dependent deacetylase belonging to the sirtuin family, which regulates a broad spectrum of cellular processes through deacetylation of both histones in the nucleus and non‐histone proteins in the cytosol. Accumulating evidence indicates that biological aging is associated with a marked decline in the expression and activation of SIRT1 /SIRT1, which contributes to the onset and progression of various age‐related diseases. Conversely, activation of SIRT1 has been shown to mitigate aging‐associated cellular anomalies including mitochondrial dysfunction, oxidative stress, and cellular senescence. In this review, we summarize recent advances in understanding the role of SIRT1 in aging and age‐associated diseases across various experimental models, and we also discuss current limitations in the field as well as potential future research direction.