Maintaining Physical Fitness Is an Effective Weapon Against Age-Related Diseases

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

Regular physical activity is well known to benefit the heart, muscles and overall wellbeing. But does it also leave a measurable imprint on the body's molecular machinery? Researchers Samiha Nasser and Dr Csaba Kerepesi from the BioAgeAI Research Group at HUN-REN SZTAKI, in collaboration with Professor Zsolt Radák's research group at the Hungarian University of Sports Science, set out to investigate how physical fitness is associated with biological ageing and the risk of age-related diseases. Their findings were recently published in the prestigious research journal Aging Cell.

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.

What is an epigenetic marker?

Epigenetic markers are molecular indicators that reveal which genes are active and which are suppressed. Rather than altering the genetic information encoded in DNA itself, they regulate how genes are expressed. While the DNA sequence remains largely unchanged throughout life, epigenetic markers are dynamic: they respond to factors such as diet, stress, physical activity, sleep deprivation and exposure to environmental toxins. In recent years, they have become increasingly important in the early detection of disease and in ageing research because they provide sensitive indicators of an individual's physiological state and reflect the long-term effects of lifestyle and environmental influences.

What is DNA methylation?

DNA methylation is one of the most important epigenetic mechanisms. It involves the addition of small methyl groups to specific locations in the DNA molecule, influencing how actively a gene is expressed. The genetic code itself remains unchanged; only the regulation of gene activity is modified.

Patterns of DNA methylation change with age and are influenced by nutrition, physical activity, smoking, stress and various diseases. For this reason, researchers now use these patterns as a kind of biological fingerprint, enabling them to estimate an individual's biological age and the risk of developing certain 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.