Chapter 11 - Role of AMP-activated protein kinase and sirtuins as antiaging proteins

Abstract

AMP-activated protein kinase (AMPK) and sirtuins are fuel-sensing enzymes. AMPK is activated upon increased AMP/ATP ratio, and sirtuins activation increases by increased NAD+ levels. There are seven isoforms of sirtuin (SIRT1-SIRT7) expressed at different cellular compartments. The most studied sirtuin isoform in the context of aging is SIRT1. SIRT1 and AMPK pathways are correlated and might have coexisted during evolution. They are involved in various age-related processes as they share common cellular targets. Multiple studies have revealed that increased AMPK and sirtuin activity can extend the lifespan of an organism. However, with age, the responsiveness of AMPK and SIRT1 reduces, which affects mitochondrial function, metabolism, increases oxidative stress and promotes inflammation. Increased activity of AMPK and SIRT1 has antiaging effects as observed in different species, and therefore they are believed to serve as potential therapeutic targets to treat age-related disorders. AMPK and SIRT1 activators are considered promising treatment approaches for diabetes, metabolic and mitochondrial disorders, and neurodegeneration. However, the mechanism of action of AMPK and sirtuin modulators is a subject of future research, and rigorous validation of these compounds are required before exploiting these compounds in the treatment of age-associated disorders.