The mitochondrial side of frailty
Emanuele Marzetti1,2, Rosa Di Lorenzo3, Anna Picca1,4
1Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS.
Current Opinion in Clinical Nutrition and Metabolic Care
|October 12, 2025
Summary
Mitochondrial dysfunction contributes to frailty in older adults, impacting muscles, metabolism, and immunity. Research highlights potential biomarkers and interventions like exercise to improve mitochondrial health and extend healthspan.
Area of Science:
- Gerontology
- Mitochondrial Biology
- Biomarker Discovery
Background:
- Frailty is a geriatric condition characterized by reduced physiological reserve and increased vulnerability.
- Mitochondrial dysfunction is increasingly recognized as a key factor in the development of frailty.
Purpose of the Study:
- To review current evidence linking mitochondrial quality control, bioenergetics, and signaling to frailty.
- To explore potential biomarkers and the translational applications of this research.
Main Methods:
- Review of preclinical and human studies on mitochondrial dysfunction in frailty.
- Analysis of data on mitochondrial biogenesis, dynamics, mitophagy, and cellular respiration.
- Exploration of metabolomic changes and potential biomarker candidates.
Main Results:
- Impaired mitochondrial function (biogenesis, dynamics, mitophagy) contributes to frailty, sarcopenia, and immune issues.
- Frail individuals show reduced mitochondrial DNA, lower respiratory capacity, increased reactive oxygen species, and altered metabolomics.
- Potential biomarkers include mitochondria-derived vesicles and peripheral blood mononuclear cell respiration.
Conclusions:
- Mitochondrial dysfunction is central to the musculoskeletal, metabolic, and immune changes in frailty.
- Integrative biomarker panels show promise, but early diagnosis and personalized therapies are needed.
- Longitudinal studies are crucial for establishing causality and guiding precision medicine for healthspan extension.
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