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The influence of obesity, exercise and diet on age-related skeletal muscle deterioration

Project Description

Obesity increases the risk of cardiovascular and metabolic diseases and is increasing in prevalence at an alarming rate. On a relative basis, obesity incidence is highest in middle-aged and older adults, which is concerning when one considers the current demographic shift to an ageing population. The incidence of metabolic disease in older age is driven, in large part, by the gradual loss in skeletal muscle mass that occurs from approx. 50 years of age. This age-associated muscle loss is also associated with reduced strength, impaired locomotion/function and increased risk of frailty, falls, and mortality. Importantly, the presence of obesity in older age is thought to exacerbate the rate of skeletal muscle deterioration. As such, understanding the mechanistic links between obesity and muscle wasting in older age will aid the development of interventions to promote ‘high quality’ weight loss (i.e. preferential loss of fat over lean tissue mass) and improved metabolic health in overweight and obese older adults. Such interventions have the potential to reduce the incidence of age-associated comorbidities and extend the number of years lived in good health, with important implications for healthcare expenditure.

In the first phase of the proposed PhD project, in vitro cell culture experiments will be performed to understand how translational signaling response to various stimuli (i.e. amino acids, contraction) differ in ageing and obesity. These initial cell culture experiments will be followed-up by in vivo human experimental studies, in which muscle biopsy samples will be obtained from obese and normal-weight older adults under conditions of nutrient consumption and exercise. Cutting edge methodology will be used to deliver key mechanistic insights into the role of obesity in the regulation of muscle mass in older age. Finally, In the second phase of this PhD studentship, a large cohort of obese older adults will complete a short-term diet and exercise intervention, in partnership with the newly developed UoB Sport & Fitness Centre. Dietary intake will be manipulated to promote ‘high quality’ weight loss. Comprehensive tests of physiological function and anthropometrics will be performed before and after the intervention. In addition, muscle biopsy and blood samples will be obtained before and after the intervention and used to determine cellular growth processes using in vitro cell culture models. Muscle and blood samples will also be analyzed for changes in cellular regulators of muscle protein turnover and inflammation.

This project will provide the selected student with unique access to numerous research approaches across a broad range of disciplines (molecular biology, nutritional biochemistry, metabolic physiology). Specifically, the initial phase of this project will combine in vitro cell-based screening approaches with detailed metabolic phenotyping in pre-clinical models, allied to molecular biology techniques including (but not limited to) western blot, qRT-PCR, immunoflouresence microscopy and stable isotope tracers. Human in vivo studies will incorporate a range of metabolic and physiological testing techniques (i.e. maximal strength, aerobic fitness), exercise training programming and delivery, and dietary analysis. Therefore, this project it will provide a true bench-to-patient pipeline of investigation.

Funding Notes

This position is funded through the Midlands Integrative Biosciences Training Partnership, a 4-year PhD scholarship including a 1st year skills training. Details of the funding and support provided through the MIBTP scheme can be found at:

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