Mitochondrial dysfunction as a biomarker of frailty: The FRAMITO study protocol
Edoardo Locatelli1, Barbara Torsello2, Sofia De Marco2
1Department of Medical Science, University of Ferrara, 44121 Ferrara, Italy; Geriatrics and Orthogeriatrics Unit, Azienda Ospedaliero-Universitaria of Ferrara, 44121 Ferrara, Italy.
Archives of Gerontology and Geriatrics
|March 5, 2025
Summary
This study investigates mitochondrial dysfunction in older adults with frailty and multimorbidity. Findings may reveal new biomarkers and therapeutic targets for these complex conditions.
Area of Science:
- Gerontology
- Mitochondrial Biology
- Biomarker Discovery
Background:
- Frailty syndrome frequently co-occurs with multimorbidity in older adults.
- Shared risk factors and outcomes highlight the interconnectedness of these conditions.
- Current research on frailty biomarkers primarily focuses on inflammation, neglecting mitochondrial dysfunction markers.
Purpose of the Study:
- To evaluate mitochondrial dysfunction in individuals with frailty, both with and without multimorbidity.
- To explore potential synergistic effects of frailty and multimorbidity on mitochondrial health.
- To identify novel biomarkers associated with mitochondrial dysfunction in aging and complex health conditions.
Main Methods:
- Cross-sectional study of 75 participants aged ≥65 years, categorized into three groups: no frailty/multimorbidity, frailty only, and frailty with multimorbidity.
- Isolation of Peripheral Blood Mononuclear Cells (PBMCs) from blood samples.
- Assessment of mitochondrial dysfunction using untargeted metabolomics and functional assays, including mitochondrial DNA damage, cellular bioenergetics (mitochondrial and glycolytic), and reactive oxygen species levels.
Main Results:
- (Study results are pending as this is a protocol description) The FRAMITO project will analyze mitochondrial DNA damage, cellular bioenergetics, and oxidative stress markers in PBMCs.
- Metabolomic profiling will identify potential biomarkers related to mitochondrial dysfunction.
- Functional studies will elucidate the impact of frailty and multimorbidity on cellular energy production and oxidative balance.
Conclusions:
- This research will enhance understanding of the pathophysiology of frailty, particularly its interplay with multimorbidity.
- The study aims to uncover novel mitochondrial dysfunction biomarkers for frailty.
- Findings may pave the way for targeted interventions addressing mitochondrial health in aging populations with complex conditions.


