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Updated: Jun 13, 2025
Measurement of Protein Turnover Rates in Senescent and Non-Dividing Cultured Cells with Metabolic Labeling and Mass Spectrometry
Published on: April 6, 2022
Aged bone marrow macrophages drive systemic aging and age-related dysfunction via extracellular vesicle-mediated
Jing Hou1, Kai-Xuan Chen1, Chen He1
1Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, China.
Abstract:
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.
Insights
Physiologically aged bone marrow monocytes/macrophages (BMMs) spread senescence via extracellular vesicles (EVs), driving age-related dysfunction. Fenofibrate treatment restored homeostasis and may extend healthy lifespan.
Area of Science:
- Cellular senescence
- Aging biology
- Immunology
Background:
- Cellular senescence accumulation drives aging and age-related diseases.
- The specific cell types responsible for senescence propagation remain unclear.
Purpose of the Study:
- Identify cell types propagating senescence in aging.
- Investigate mechanisms of senescence propagation.
- Evaluate therapeutic interventions for age-related dysfunction.
Main Methods:
- Analysis of aged bone marrow monocytes/macrophages (BMMs) and their extracellular vesicles (EVs).
- In vivo studies in aged mice.
- MicroRNA analysis within EVs.
- Cohort study of 7,986 human participants.
Main Results:
- Aged BMMs propagate senescence to multiple tissues via EVs, causing age-associated dysfunction in mice.
- Peroxisome proliferator-activated receptor α (PPARα) was identified as a key target within aged BMM-EVs.
- Fenofibrate treatment restored tissue homeostasis in aged mice.
- Fenofibrate use in humans correlated with reduced chronic disease risk and increased life expectancy.
Conclusions:
- Bone marrow monocytes/macrophages are key drivers of senescence propagation and age-related dysfunction.
- PPARα signaling is a critical mediator of age-related dysfunction.
- Fenofibrate shows therapeutic potential for extending healthy lifespan and mitigating age-related diseases.
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