Research progress in the role of SIRT6 in aging and metabolism

SIRT6, a member of the sirtuin family of histone deacetylases, belongs to the class Ⅲ longevity proteins and exhibits NAD+-dependent deacetylase and mono-ADP-ribosyltransferase activities. SIRT6 is primarily located in the cell nucleus and plays a pivotal role in regulating genomic stability and relative gene expression, participating in the control of key processes such as energy metabolism and aging. Given its crucial role in maintaining cellular homeostasis and organismal health, SIRT6 has emerged as a potential therapeutic target, sparking significant research interest in the development of targeted modulators. Activating the longevity protein with drugs may provide therapeutic strategies for age-associated diseases, including aging, metabolic syndrome, inflammation, and reproductive health issues. The review elaborates the structural characteristics, enzymatic activities, and biological functions of SIRT6, as well as the mechanisms of action, pharmacological activities, and clinical applications of various SIRT6 activators.