The sirtuin family of proteins has attracted research interest for its involvement in mechanisms that may influence the pace of aging. While the overhyped work on the effects of sirtuin 1 on aging unraveled to produce no practical applications, sirtuin 3, sirtuin 4, and sirtuin 5 are localized in the mitochondria and there is a range of more convincing evidence to suggest that they can be manipulated to meaningfully adjust mitochondrial function in later life.
Sirtuins, colloquially termed "longevity proteins," are central regulators in the intricate molecular networks of aging. These proteins function as nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases or adenosine diphosphate (ADP)-ribosyltransferases, operating within multiple cellular regulatory pathways crucial to the aging process. The mammalian sirtuin family comprises seven members (SIRT1-7), with SIRT3, SIRT4, and SIRT5 specifically localized to the mitochondria.
These mitochondrial sirtuins have garnered significant scientific interest due to their potential roles in aging and age-associated disorders, primarily through their involvement in maintaining mitochondrial function and energy metabolism. Through the regulation of mitochondrial metabolism, stress response pathways, and other cellular processes, these proteins contribute to the maintenance of mitochondrial integrity and function, thereby supporting overall cellular homeostasis.
The diverse actions of mitochondrial sirtuins contribute to delaying age-related functional decline in various organs and extending lifespan in model organisms, positioning them as central players in the complex biology of aging. Given their critical roles in regulating aging, a systematic review of SIRT3, SIRT4, and SIRT5 functions in aging and age-related diseases is warranted. This review aims to provide a comprehensive overview of the current understanding of mitochondrial sirtuins, focusing on their involvement in various aging processes and their roles in age-related pathologies.
Link: https://doi.org/10.1093/lifemedi/lnaf019
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