May 19th, 2026

Despite the failure to produce any useful approach to therapy based on upregulation of sirtuin 1 expression, and an entirely unhelpful hype cycle that came and went associated with those efforts, research into sirtuin 1 continues apace. In the example here, researchers connect sirtuin 1 expression to the improved metabolism following exercise. As is usual in matters of cellular biochemistry, connecting specific benefits to specific mechanisms is challenging; a great deal changes with exercise, and it has hard to say which of those changes are more versus less important.

Sirtuin 1 (SIRT1) was initially identified as an enzyme that deacetylates histones and suppresses gene activity. Since then, its roles have expanded considerably, and it is now recognized as a multifunctional protein conserved across various organisms. Despite increasing interest, it remains essential to clarify how exercise-induced changes in SIRT1 counteract multiple hallmarks of aging, as well as the full scope of SIRT1's impact on different physiological systems. This review highlights recent findings on the short- and long-term effects of exercise on SIRT1 signaling in both rodents and humans during aging. We explore the molecular pathways activated in various tissues, providing insight into the specific biological functions of SIRT1 within aging cells.