近日，香港中文大学教授Ho Ko及其课题组的最新研究提出了衰老与GLP-1R激动作用的全身多基因组对抗。相关论文于2025年11月19日发表在《细胞—代谢》杂志上。

该研究组对衰老雄性小鼠进行了深入的分子分析和功能评估，结果表明胰高血糖素样肽-1受体激动剂（GLP-1RA）治疗广泛地抵消了与年龄相关的变化。在用GLP-1RA治疗11个月至30周的小鼠中，研究小组观察到强大的全身多组年龄抵消作用，并改善了选定的身体功能。重要的是，这种效果是针对老年小鼠的，而不是年轻的成年小鼠，并且是在相对较低的剂量下达到的，对食物摄入或体重的影响最小。从18个月开始GLP-1RA治疗，持续13周，分子年龄抵消效果更强，很大程度上依赖于下丘脑GLP-1R，指向衰老调节的脑-体轴。与哺乳动物雷帕霉素靶点（mTOR）抑制的比较显示出强烈的多组相似性，雷帕霉素靶点抑制是一种成熟的抗衰老策略。他们的发现对GLP-1RAs多效性的机制具有广泛的意义，指导临床试验，并为抗衰老疗法的发展提供信息。

研究人员表示，迫切需要确定实际的方法来对抗衰老和相关的退行性疾病。

附：英文原文

Title: Body-wide multi-omic counteraction of aging with GLP-1R agonism

Author: Junzhe Huang, Andrew J. Kwok, Jason Chak Yan Li, Clement Lek Hin Chiu, Bonaventure Y. Ip, Lok Yi Tung, Roy C.H. Chan, Danny C.W. Chan, Ziyu Wang, Xianyi Zheng, Hoi Tung Chow, Michelle P.S. Lo, Zhongqi Li, Nenghan Lin, Manyu Wang, Leo Y.C. Yan, William K.K. Wu, Kim Hei-Man Chow, Wei-Jye Lin, Yamei Tang, Yun Zhang, Weihong Song, Billy Wai-Lung Ng, Sunny H. Wong, Thomas W. Leung, Vincent C.T. Mok, Ho Ko

Issue&Volume: 2025-11-19

Abstract: 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.

DOI: 10.1016/j.cmet.2025.10.014

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00474-7