Comparing the Phenotypes and Trajectories of Human Aging Associated with Exercise or Inactivity

Simply Put

This project aims to increase our understanding of the biology of human aging. As many aspects of getting older are also associated with physical inactivity, this study will investigate groups of both sedentary and physically active young and older people to separate out the effects of aging from the negative effects of inactivity. With a specific focus on muscle and the immune system, our project will combine a unique series of physiological, cellular and molecular investigations to provide further insight in to how the body ages.

Description

This research project seeks to better understand the physiology of human aging and, in particular, to disentangle aging from inactivity-mediated processes. It will perform detailed investigations on young and old, active and inactive, males and females.  There is a particular focus on skeletal muscle and the immune system. The project will use a range of approaches from whole-body physiology to deep molecular phenotyping of cells to address the research aims.

The aged active cohort is represented by 125 master cyclists (84 male, 41 female) first sampled in 2012/13 when they were 55-79 years old. Re-testing of the master cyclists is planned to begin in April / May 2021 when the participants will be 64-88 years old. This will form a nested and unique longitudinal study within the larger cross-sectional project.

In addition to the active older participants, a new cohort of age-matched sedentary individuals (male and females) will be studied in 2021.  This will provide a cross-sectional comparison with the active cohort. The amount of physical activity will be quantified through, training diaries, questionnaire and actigraphy in the week prior to testing. In addition, two groups of young participants aged 18-35 years will be also investigated in this study: 20 young cyclists (10 males and 10 females) and 20 sedentary individuals (10 males and 10 females). This will enable the differentiation of the effects of aging from inactivity processes.

The following analyses will be carried out:

1. Full physiological phenotyping for all cohorts will include measures of: cardiorespiratory fitness (VO₂max), O2 uptake kinetics, blood pressure, lung function, body composition and bone mineral density (DXA), muscle strength and power, nerve conduction velocity, balance, cognitive function,  as well assessment of nutrition, sleep and quality of life.
2. Blood samples will be taken for indices of metabolic health, hormonal status and inflammation.
3. Immune cells will be isolated and phenotype to assess the degree of immune aging.
4. Muscle biopsy samples will be analysed for changes in muscle fibre size, type mitochondrial complex protein content, capillarisation as well as markers of senescence.
5. In addition to muscle, fat and skin biopsies will be obtained assessed for markers of aging process e.g. DNA methylation.  In a collaboration with Dr Maxmim Artyomov (Washington University School of Medicine in St Louis) samples obtained from this study be profiled using multi-omics approaches; including single-cell RNA-seq including TCR-repertoire and CyTOF chromatin profiling, single-cell nuclear RNA-seq, and Whole Genome Bisulfite Sequencing for epigenetic changes.
6. The molecular data from the tissue samples will be integrated with the in vivo physiological data obtained from the participants.

Results

The first phase of testing on young participants (cyclists and sedentary individuals) and on master cyclists is ongoing.