Mitochondrial sirtuins, key regulators of aging

Abstract Mitochondrial dysfunction is a hallmark of aging, characterized by a decline in mitochondrial biogenesis and quality control, compromised membrane integrity, elevated ROS production, damaged mitochondrial DNA (mtDNA), impaired mitochondrial–nuclear crosstalk, and deregulated metabolic balance. Among the key longevity regulators, sirtuin family members SIRT3, SIRT4, and SIRT5 are predominantly localized to mitochondria and play crucial roles in maintaining mitochondrial function and homeostasis. This review explores how mitochondrial sirtuins mitigate aging-related mitochondrial dysfunctions and their broader implications in aging-related diseases. By elucidating the intricate interplay between mitochondrial dysfunction and mitochondrial sirtuins, we aim to provide insights into therapeutic strategies for promoting healthy aging and combating age-related pathologies.