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Sample Preparation to Bioinformatics Analysis of DNA Methylation: Association Strategy for Obesity and Related Trait Studies
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Physical Fitness Is Negatively Associated With DNA Methylation-Based Risk of Aging-Related Diseases
Samiha Nasser1,2, Johanna Keringer3, Yaodong Gu4
1HUN-REN Institute for Computer Science and Control (SZTAKI), Budapest, Hungary.
Aging Cell
|April 8, 2026
Summary
Physical fitness, measured by DNA methylation-based protein estimates (EpiScores), links to aging-related disease risk. This study reveals molecular markers for personalized disease prevention and risk stratification.
Area of Science:
- Epigenetics and molecular biology
- Gerontology and aging research
- Personalized medicine and disease prevention
Background:
- Physical fitness is crucial for health, but its molecular links to aging-related diseases are not fully understood.
- DNA methylation-based protein level estimates (EpiScores) offer a molecular window into biological processes.
- Understanding these links can aid in early disease risk stratification and prevention.
Purpose of the Study:
- To investigate associations between DNA methylation-based protein estimates (EpiScores) and key fitness traits.
- To explore the molecular pathways connecting physical fitness, protein levels, and aging-related disease risk.
- To develop a workflow for patient-level disease risk assessment using DNA methylation and fitness data.
Main Methods:
- EpiScores for 109 plasma proteins were generated using the MethylDetectR tool.
- Associations between EpiScores and five fitness traits (VO2max, Grip Strength, Jump Max, BMI, cognition) were analyzed in 290 older adults.
- EpiScore-disease associations were integrated to identify overlapping pathways.
Main Results:
- 33 significant associations were found between fitness traits and protein EpiScores, independent of age and sex.
- 51 fitness predictor-disease associations were identified, linking traits like BMI, cognition, grip strength, and jump performance to various chronic diseases.
- A validated workflow for patient-level disease risk assessment using DNA methylation and fitness measurements was developed.
Conclusions:
- Protein EpiScores serve as interpretable molecular markers connecting physical and cognitive fitness to aging-related disease risk.
- These findings support the potential of EpiScores for early disease risk stratification and personalized prevention strategies.
- The study highlights the intricate molecular interplay between fitness, protein expression, and chronic disease development.
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