Extracellular vesicles in disease
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It is found that physiologically aged bone marrow monocytes/macrophages can propagate senescence to multiple tissues in vivo, through extracellular vesicles containing PPARα-targeted microRNAs, and fenofibrate use is associated with a reduced risk of age-related chronic disease and higher life expectancy.
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The accumulation and systemic propagation of senescent cells contributes to physiological aging and age-related pathology. However, which cell types are most susceptible to the aged milieu and could be responsible for the propagation of senescence has remained unclear. Here we found that physiologically aged bone marrow monocytes/macrophages (BMMs) propagate senescence to multiple tissues, through extracellular vesicles (EVs), and drive age-associated dysfunction in mice. We identified peroxisome proliferator-activated receptor α (PPARα) as a target of microRNAs within aged BMM-EVs that regulates downstream effects on senescence and age-related dysfunction. Demonstrating therapeutic potential, we report that treatment with the PPARα agonist fenofibrate effectively restores tissue homeostasis in aged mice. Suggesting conservation to humans, in a cohort study of 7,986 participants, we found that fenofibrate use is associated with a reduced risk of age-related chronic disease and higher life expectancy. Together, our findings establish that BMMs can propagate senescence to distant tissues and cause age-related dysfunction, and they provide supportive evidence for fenofibrate to extend healthy lifespan.
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@article{Hou2024Aged,
title = {Aged bone marrow macrophages drive systemic aging and age-related dysfunction via extracellular vesicle-mediated induction of paracrine senescence},
author = {Jing Hou and Kaixuan Chen and Chen He and Xiaoxiao Li and Mei Huang and Yangzi Jiang and Yurui Jiao and Qiao-Ni Xiao and Wenzhen He and Ling Liu and Nan-Yu Zou and Min Huang and Jie Wei and Ye Xiao and Mi Yang and Xiang‐Hang Luo and Chao Zeng and Guanghua Lei and Changjun Li},
journal = {Nature Aging},
year = {2024},
doi = {10.1038/s43587-024-00694-0},
url = {https://doi.org/10.1038/s43587-024-00694-0}
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