Sirtuin 1 - Peroxisome proliferator-activated receptor gamma coactivator 1-alpha pathway (SIRT1–PGC-1α pathway)

The Sirtuin 1 – Peroxisome proliferator-activated receptor gamma coactivator 1-alpha pathway (SIRT1–PGC-1α pathway) refers to the regulatory interaction between SIRT1, an NAD+-dependent protein deacetylase, and PGC-1α, a high-level transcriptional co-activator that controls genes involved in energy metabolism, mitochondrial biogenesis, and antioxidant responses. SIRT1 directly deacetylates PGC-1α, enhancing its transcriptional activity; this axis is central to adaptation to metabolic and oxidative stress, and has been implicated in multiple diseases including metabolic syndrome, neurodegeneration, and cardiovascular disease. The pathway, not a single protein, includes two distinct but interacting therapeutic targets—each regulated by different molecules and mechanisms. This entry is not suitable as a single structured target but refers to an important cellular pathway with multiple nodes for pharmacologic intervention. For SIRT1 or PGC-1α as individual targets, see entries under “Sirtuin 1” or “Peroxisome proliferator-activated receptor gamma coactivator 1-alpha.”

Other names

SIRT1–PGC-1α axisSirtuin 1–PGC-1α signaling pathwaySirt1-PGC1α pathway

SIRT1 activators promote deacetylation and activation of PGC-1α, leading to enhanced mitochondrial biogenesis and function. Drugs indirectly increase cellular energy metabolism, antioxidant defense, and reduce apoptosis through pathway activation.