A review of sirtuin biology maps this NAD+-dependent enzyme family onto the established hallmarks of aging as they manifest in skin, covering genomic stability, mitochondrial function, cellular senescence, inflammation, and autophagy. Sirtuin activity declines with chronological age and is further suppressed by ultraviolet exposure, degrading barrier integrity and keratinocyte stem cell maintenance. Skin becomes a visible, accessible readout of enzymatic processes operating throughout the body.
Key Points
- Sirtuins regulate genomic stability, mitochondrial function, senescence, and autophagy
- UV exposure suppresses sirtuin activity beyond age-related decline alone
- Declining sirtuins compromise barrier integrity and keratinocyte stem cell maintenance
Longevity Analysis
Skin offers a rare opportunity to observe aging mechanics directly, and sirtuin decline links visible changes to the same mitochondrial and repair processes operating in less accessible tissue. The dual insult — chronological decline compounded by ultraviolet damage — places photoprotection ahead of any supplementation strategy in order of operations, since continued UV exposure actively suppresses the enzymes that support cellular repair and regulate the inflammatory signaling behind barrier breakdown. NAD+ availability constrains sirtuin function, making energy metabolism and the tissue's capacity to renew itself inseparable considerations rather than parallel ones.
Original published by Wiley Aging Cell, by Rishabh Kala, Antonella Rella, Whitby Eagle, Earl Goyarts, Jian Cao, Binwei Deng, Kelly Dong, Chloe Schmit, Matthew Cappock, Krystle Corallo, Jacqueline Trivero .