SIRT1 and SIRT6: The role in aging-related diseases

Aging is characterized by progressive functional deterioration with increased risk of mortality. It is a complex biological process driven by a multitude of intertwined mechanisms such as increased DNA damage, chronic inflammation, and metabolic dysfunction. Sirtuins (SIRTs) are a family of NAD⁺-dependent enzymes that regulate fundamental biological functions from genomic stability and lifespan to energy metabolism and tumorigenesis. Of the seven mammalian SIRT isotypes (SIRT1-7), SIRT1 and SIRT6 are well-recognized for regulating signaling pathways related to aging. Herein, we review the protective role of SIRT1 and SIRT6 in aging-related diseases at molecular, cellular, tissue, and whole-organism levels. We also discuss the therapeutic potential of SIRT1 and SIRT6 modulators in the treatment of these diseases and challenges thereof.