Cell metabolism · 2025
Body-wide multi-omic counteraction of aging with GLP-1R agonism.
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Huang Junzhe, Kwok Andrew J, Li Jason Chak Yan, Chiu Clement Lek Hin, Ip Bonaventure Y, Tung Lok Yi, Chan Roy C H, Chan Danny C W, Wang Ziyu, Zheng Xianyi, Chow Hoi Tung, Lo Michelle P S, Li Zhongqi, Lin Nenghan, Wang Manyu, Yan Leo Y C, Wu William K K, Chow Kim Hei-Man, Lin Wei-Jye, Tang Yamei, Zhang Yun, Song Weihong, Ng Billy Wai-Lung, Wong Sunny H, Leung Thomas W, Mok Vincent C T, Ko Ho
Аннотация
Identifying practical ways to counteract aging and associated degenerative disorders is urgently needed. We performed deep molecular profiling and functional assessments in aging male mice to show that glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment broadly counteracts age-related changes. In mice treated with a GLP-1RA from 11 months for 30 weeks, we observed strong body-wide multi-omic age-counteracting effects and improved selected physical functions. Importantly, the effects were specific to aged mice, not young adults, and were attained with a relatively low dose that minimally affected food intake or body weight. With GLP-1RA treatment beginning at 18 months for 13 weeks, the molecular age-counteracting effects were even stronger and largely dependent on hypothalamic GLP-1R, pointing to a brain-body axis of aging modulation. Comparison with mammalian target of rapamycin (mTOR) inhibition, a proven anti-aging strategy, revealed strong multi-omic similarities. Our findings have broad implications for the mechanisms behind GLP-1RAs' pleiotropic benefits, guiding clinical trials, and informing development of anti-aging-based therapeutics.