Sirtuin 1 as an emerging exerkine in the aging process: unveiling its multifaceted biological roles

Apr 28, 2026Biogerontology

Sirtuin 1 as a new exercise-related protein with multiple roles in aging

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Abstract

SIRT1 levels can be increased through various exercise protocols in multiple vital organs of aged animals and older adults.

SIRT1 is involved in regulating key biological processes such as mitochondrial function, metabolism, and inflammation.
Optimal SIRT1 levels are associated with maintaining homeostasis and promoting healthspan during aging.
Exercise may stimulate SIRT1 activity, acting as a sensor for the benefits of physical activity.
The review highlights both short- and long-term effects of exercise on SIRT1 signaling in humans and rodents.
Different types of exercise, including aerobic and resistance training, can elevate SIRT1 expression in tissues like the heart and skeletal muscle.

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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. Optimal levels of SIRT1 help maintain homeostasis and a biochemical environment conducive to healthspan, influencing biological processes such as mitochondrial dynamics, metabolic pathways, tissue remodeling, autophagy, inflammatory responses, and redox balance. This indicates that SIRT1, a pleiotropic molecule, orchestrates multiple responses throughout aging. SIRT1 may act as a dynamic sensor for exercise benefits and protect against aging by maintaining genomic integrity. Different exercise protocols (acute and chronic) and modalities (aerobic, resistance, and combined training) can increase mRNA levels, activity, or protein levels of SIRT1 in various vital organs (adipose tissue, hippocampus, heart, liver, bone, and skeletal muscle) of aged animals and older adults, promoting health. Taken together, these observations support the notion that SIRT1 functions as a potential exerkine, and understanding its role in exercise-induced adaptations offers new insights into non-pharmacological strategies to enhance longevity.

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Sirtuin 1 as an emerging exerkine in the aging process: unveiling its multifaceted biological roles

Abstract

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