Age-related decline in the sirtuin AcSirt2 impairs mitochondrial quality control in honey bees, while restoring this protein activates a FOXO-dependent pathway that clears damaged mitochondria, reduces oxidative stress, and extends lifespan. This mechanism identifies a conserved axis for mitochondrial homeostasis relevant to aging across species.
Key Points
- AcSirt2 decline drives age-related mitochondrial dysfunction and ROS accumulation
- AcSirt2 restoration activates PINK1/Parkin mitophagy, clearing damaged organelles
- AcSirt2-FOXO axis extends lifespan and preserves locomotor function in vivo
Longevity Analysis
Mitochondrial dysfunction is a hallmark of aging in virtually all organisms. This research demonstrates that sirtuin-mediated deacetylation of FOXO coordinates a protective response—maintaining the balance between mitochondrial fusion and fission, activating selective autophagy of damaged organelles, and restoring energy production capacity. The pathway operates at the intersection of energy metabolism and cellular cleanup; when sirtuin activity declines with age, this dual failure accelerates senescence. Interventions that preserve or restore this axis offer a mechanism to sustain mitochondrial integrity and delay age-related decline, with direct implications for designing therapies that support cellular energy systems and reduce oxidative burden.
Original published by Wiley Aging Cell, by Qiang Ma, Zhengang Ma, Tingyue Huang, Qianmin Hai, Xiaoqun Dang, Jinshan Xu, Jialing Bao, Zachary Y. Huang, Zeyang Zhou .