Understanding the influence of physical activity on ageing processes

Background: The increase in human longevity across the globe is a major challenge for society as old age is associated with increased risk of chronic disease and most older adults have more than one condition. How well we age is influenced by a range of factors including lifestyle behaviours such as physical activity.

We now understand the biological processes that cause the aged phenotype, these are termed the Hallmarks of Ageing.

They include primary drivers (damage to DNA and proteins) and the secondary responses that induce the aged phenotype, including cell senescence and inflammation.

What is not known is whether lifestyle influences these core ageing processes to mediate its effects on lifespan and healthspan. This is the core question addressed in this proposal, with a focus on physical activity.

Additionally, methods have been developed that allow determination of an individual’s overall biological age as opposed to their chronological age and these will be used to determine the broader impact of physical activity on ageing.

Hypothesis: This project will test the hypothesis that regular physical activity can slow biological ageing by minimising core ageing processes, with a focus on cell senescence and its associated systemic inflammation.

Methods: Professor Lord, working with Professor Harridge at KCL, has previously set up a cohort of 125 regular exercisers (master cyclists) aged 55-79-years who have been very physically active most of their adult lives. The cohort was deeply phenotyped in 2012 and showed few signs of ageing physiologically.

There is a rich physiological and molecular dataset and stored tissues (blood cells and muscle) available for this cohort, though cell senescence was not investigated. In 2020 they are sampling the cohort again and with matched young cyclists and young and old non-exercisers. They will also collect a broader range of tissues (skin, blood cells, muscle and adipose tissue).

This project will use this cohort to meet the following objectives: 1.

Perform a systematic review and meta-analysis of the literature, regarding the effects of physical activity on the core processes driving ageing. 2.

Analyse tissue samples from the young exercisers and non-exercisers, and old exercisers and non-exercisers to quantify the presence of senescent cells and to assess systemic inflammation in serum. 3.

To use a composite measure of an individual’s biological age, based on DNA methylation in blood cells, in a subset of the older adults to determine if maintained PA reduces overall biological ageing.