细胞外小泡
能量代谢
线粒体
细胞外
新陈代谢
细胞生物学
小泡
化学
生物
生物物理学
生物化学
内分泌学
膜
作者
Hong Chen,Yang Luo,Qing Zhu,Jingzi Zhang,Huan Huang,Yi Kan,Dian Li,Min Xu,Shuohan Liu,Jianxiao Li,Juan Perucho,Li Zhang,Yan Hui Guo,Binghao Wang,Guantong Qi,Zhen Zhou,Chen-Yu Zhang,Lei Fang,Yanbo Wang,Xi Chen
出处
期刊:Nature Aging
日期:2024-04-16
标识
DOI:10.1038/s43587-024-00612-4
摘要
Abstract Recent investigations into heterochronic parabiosis have unveiled robust rejuvenating effects of young blood on aged tissues. However, the specific rejuvenating mechanisms remain incompletely elucidated. Here we demonstrate that small extracellular vesicles (sEVs) from the plasma of young mice counteract pre-existing aging at molecular, mitochondrial, cellular and physiological levels. Intravenous injection of young sEVs into aged mice extends their lifespan, mitigates senescent phenotypes and ameliorates age-associated functional declines in multiple tissues. Quantitative proteomic analyses identified substantial alterations in the proteomes of aged tissues after young sEV treatment, and these changes are closely associated with metabolic processes. Mechanistic investigations reveal that young sEVs stimulate PGC-1α expression in vitro and in vivo through their miRNA cargoes, thereby improving mitochondrial functions and mitigating mitochondrial deficits in aged tissues. Overall, this study demonstrates that young sEVs reverse degenerative changes and age-related dysfunction, at least in part, by stimulating PGC-1α expression and enhancing mitochondrial energy metabolism.
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