Physical fitness benefits more than just your muscles – it may also favourably influence the cellular processes of ageing

The researchers started from the observation that people do not age at the same rate. Two individuals of the same chronological age may differ considerably in terms of their biological age, with one person's body effectively being "younger" than the other's. To investigate this, the team used epigenetic markers that estimate the levels of specific proteins based on patterns of DNA methylation. These so-called EpiScores are playing an increasingly important role in predicting biological ageing and the risk of a wide range of diseases.

The study included 290 participants with a mean age of 60 years. The researchers analysed five characteristics that reflect physical and cognitive performance: maximal oxygen uptake (VO₂max), handgrip strength, lower-body power assessed by jump performance, body mass index (BMI), and cognitive performance. These measures were then compared with epigenetic markers representing 109 protein EpiScores, allowing the researchers to investigate how physical and cognitive fitness are associated with the molecular risk profiles of age-related diseases.

"One of the novel aspects of our study is that we did not examine physical performance in isolation but analysed it together with molecular information derived from DNA methylation. This approach helps us better understand the biological mechanisms through which good physical fitness may contribute to healthy ageing," emphasised Csaba Kerepesi, one of the researchers involved in the study.

The findings revealed a clear pattern: better physical fitness was associated with more favourable molecular profiles. Greater handgrip strength and better jump performance were linked to lower epigenetic risk profiles for several conditions, including type 2 diabetes, chronic obstructive pulmonary disease (COPD), stroke and lung cancer. Better cognitive performance was likewise associated with more favourable molecular signatures, whereas higher body mass index was linked to increased molecular risk for several age-related diseases, including diabetes, coronary artery disease, stroke and depression. Overall, the researchers identified 51 significant associations linking physical or cognitive fitness with epigenetic risk markers for age-related diseases.

The researchers also developed an analytical workflow that estimates the molecular risk of disease by integrating measures of physical fitness with DNA methylation data. The resulting patient-level risk scores showed strong agreement with an independent DNA methylation-based cardiovascular disease reference model, supporting the validity of the approach. According to the researchers, this methodology could eventually contribute to the early assessment of disease risk and to more personalised preventive healthcare.

The message of the study therefore goes beyond the familiar advice that "exercise is good for you". The findings suggest that good physical fitness is associated not only with better everyday performance but also with healthier molecular ageing, indicating that regular physical activity may exert long-term effects on some of the body's most fundamental biological processes.