Title: Understanding the influence of physical activity on ageing processes
Funder: The Academy of Medical Sciences

Abstract: 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.

Lay abstract: With falling birth rates and increasing longevity we are an ageing society. This would be a cause for celebration if it were not for the fact that old age is associated with increased risk of a range of chronic diseases. How well we age is influenced by a range of factors including our lifestyle, with behaviours such as low physical activity, smoking, alcohol and obesity all reducing lifespan. We now understand the biological processes that cause ageing, but we still do not understand how something like being physically active protects us from these processes. This project aims to determine if older adults who are physically active all of their adult lives have lower levels of two of the key ageing processes, called cell senescence and inflammation. To do this the applicant will work with Professor Janet Lord who has previously assessed a group of 125 regular exercisers (master cyclists) aged 55-79 years who have been very physically active most of their adult lives. The group were tested in 2012 for a range of aspects normally associated with ageing (loss of muscle and bone, hormonal changes, decline in the immune system) and showed few signs of ageing physiologically. In 2020 Professor Lord is re-testing the group, now aged 63-87, and will also have matched young cyclists and young and old non-exercisers. This project will use these four groups to find out if being physically active leads to lower cell senescence and inflammation and in this way protects from ageing.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;METABOLIC AND ENDOCRINE;ORAL AND GASTROINTESTINAL;STROKE