ANGPTL8, a metabolic factor that increases with age, drives adipose tissue senescence through AKT2–mTOR signaling and predicts biological aging and mortality risk in humans. Genetic deletion of ANGPTL8 in mice extended lifespan and reduced age-related functional decline, identifying this pathway as a potential therapeutic target for aging.
Key Points
- ANGPTL8 levels strongly predict biological aging and mortality in humans
- ANGPTL8 promotes adipocyte senescence via AKT2–mTOR signaling activation
- ANGPTL8 deletion extends lifespan and attenuates aging markers in mice
Longevity Analysis
Adipose tissue functions as an endocrine organ that communicates throughout the body via signaling molecules. When adipocytes enter senescence, they shift from supporting metabolic function to promoting inflammatory and dysfunctional signaling that accelerates systemic aging. This research identifies a specific molecular driver of that transition. ANGPTL8 emerges as both a measurable biomarker of biological aging risk and a mechanistic bottleneck — blocking the AKT2–mTOR pathway downstream of ANGPTL8 reversed senescence in cell studies. For practitioners, this suggests two actionable angles: ANGPTL8 measurement could improve risk stratification beyond chronological age, and interventions targeting this signaling axis (whether genetic, pharmacological, or through metabolic modification) warrant investigation as aging-delay strategies.
Original published by Wiley Aging Cell, by Yi He, Limeng Pan, WenJun Ping, Chen Meng, Xiaoyu Meng, Yaming Guo, Ranran Kan, Yuxi Xiang, Beibei Mao, Siyi Wang, Danpei Li, Xuefeng Yu .