Mitochondrial dysfunction and aging: multidimensional mechanisms and therapeutic strategies
Pei Wei1,2,3, Xiaoyan Zhang1,2,3, Chi Yan1,2,3,4
1Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
Biogerontology
|July 9, 2025
Summary
Cellular aging drives age-related diseases, with mitochondrial dysfunction playing a key role. This review explores how metabolic changes, epigenetics, telomere damage, autophagy, and the senescence-associated secretory phenotype contribute to aging and disease.
Area of Science:
- Gerontology
- Cell Biology
- Molecular Biology
Background:
- Aging is a complex process involving cellular and organelle dysfunction.
- Increasing life expectancy worldwide highlights the urgent need to understand aging mechanisms.
- Mitochondrial dysfunction is a central pathological factor in numerous age-related diseases.
Purpose of the Study:
- To systematically review the molecular pathways linking mitochondrial dysfunction to aging.
- To explore how various mechanisms contribute to age-related cellular decline and disease.
- To identify potential therapeutic targets for delaying aging and preventing age-related diseases.
Main Methods:
- Systematic review of molecular pathways driving aging.
- Analysis of mechanisms including metabolic reprogramming, epigenetic regulation, and telomere damage.
- Examination of the roles of autophagy and the senescence-associated secretory phenotype (SASP).
Main Results:
- Mitochondrial dysfunction drives aging via metabolic reprogramming (e.g., PI3K/Akt/mTOR), epigenetic changes, telomere shortening (p53-PGC-1α axis), autophagy imbalance, and SASP.
- Sirtuins (SIRT1, SIRT3) and other factors regulate mitochondrial homeostasis.
- SASP, mediated by pathways like cGAS-STING, promotes inflammation and disease progression.
Conclusions:
- Mitochondrial dysfunction is a critical driver of aging and age-related diseases.
- Targeting pathways like sirtuins, AMPK, telomerase, metabolic reprogramming, or SASP offers therapeutic potential.
- Future research should integrate multiomics and explore organelle interactions for precise interventions.
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