Aging cellJul 26, 2026

How AcSirt2 and FOXO Control Mitochondrial Cleanup to Help Slow Aging in Asian Honey Bees

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jul 27, 2026

Abstract

AcSirt2 knockdown shortens honey bee lifespan and impairs locomotor ability.

Age-related decline of AcSirt2 in honey bee brain tissue is linked to mitochondrial damage and increased oxidative stress.
Overexpression of AcSirt2 promotes a balance between mitochondrial fusion and fission, improving mitochondrial function.
Activation of AcSirt2 enhances the mitophagy pathway, leading to better mitochondrial integrity and increased ATP production.
AcSirt2 interacts with the transcription factor FOXO and facilitates its deacetylation, which may contribute to its role in aging.
Findings suggest that the AcSirt2-FOXO-mitophagy axis could be important for delaying aging in social insects.

Simplified

Cellular senescence is closely associated with mitochondrial dysfunction. Sirtuin 2 (Sirt2), a member of the Sirtuin deacetylases family, plays a pivotal role in regulating energy metabolism and aging in mammals. However, its function in social insect aging remains unclear. Here, using the Eastern honey bee (Apis cerana) as a model, we demonstrate that the age-related downregulation of A. cerana Sirt2 (AcSirt2) in brain tissue is coupled with progressive mitochondrial damage, reactive oxygen species (ROS) accumulation, and a biphasic change in autophagy activity. Conversely, overexpression of AcSirt2 alleviates cellular senescence by promoting mitochondrial fusion/fission balance (via Mfn1, Mfn2, and Drp1), activating the PINK1/Parkin-mediated mitophagy pathway, improving mitochondrial integrity, reducing oxidative stress, and enhancing ATP production. In vivo, AcSirt2 knockdown shortens honey bee lifespan and impairs locomotor ability, whereas its activation reverses these aging phenotypes. Furthermore, we show that AcSirt2 interacts with the transcription factor FOXO and mediates its deacetylation. This study reveals for the first time that the AcSirt2-FOXO-mitophagy axis delays aging by maintaining mitochondrial homeostasis in a social insect, providing novel insights into the development of anti-aging strategies and the promotion of healthy beekeeping.

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How AcSirt2 and FOXO Control Mitochondrial Cleanup to Help Slow Aging in Asian Honey Bees

Abstract

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