Loss of the lactate receptor GPR81 drives lipid accumulation and accelerates aging hallmarks in muscle tissue. Activating GPR81 reverses these changes in both cultured cells and progeroid mice, restoring lipid oxidation capacity and muscle regeneration.
Key Points
- GPR81 activation enhances lipid oxidation and reduces intramyocellular fat
- GPR81 agonists decrease DNA damage, ROS, and senescence markers
- Treatment improves muscle regeneration in aging and progeric models
Longevity Analysis
Lipid accumulation in muscle tissue is a recognized driver of age-related functional decline. This research identifies a specific receptor—GPR81—whose activity status determines whether muscle oxidizes or stores fat, directly affecting mitochondrial function and regenerative capacity. The mechanism operates at the intersection of energy production and cellular defense: when GPR81 signaling is intact, muscle prioritizes fat oxidation over accumulation, which reduces reactive oxygen species burden and preserves DNA integrity. Because this pathway can be pharmacologically activated, it represents a targetable point for slowing muscle aging independent of exercise or dietary intervention.
Original published by Wiley Aging Cell, by Pihu Mehrotra, Sai Harsha Bhamidipati, Pedro Lei, John Toftegaard, Debanik Choudhury, Maryam Elsayed, Yali Zhang, Jianmin Wang, Shweta Chitkara, G. Ekin Atilla‐Gokcumen, Song Liu, Stelios T. Andreadis .