Research into human ageing is an area of excellence and multidisciplinary research capacity at Birmingham, as evidenced by the recent award of The MRC-ARUK Centre for Musculoskeletal Ageing Research, led by Professor Janet Lord. The Centre is a partnership between the University of Birmingham and University of Nottingham with a broad remit stretching from basic mechanisms underlying the age-related loss of muscle to interventions to minimise this process. We are in particular seeking world class early career researchers with an interest in the role played by nutrition in the ageing process:
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How under and over nutrition impact upon physical functioning
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How ageing compromises anabolic responses leading to tissue atrophy (e.g. sarcopaenia)
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Nutritional interventions to reduce the impact of ageing
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Fellows would be members of, and contribute to the activity of, the MRC-ARUK Centre for Musculoskeletal Ageing Research. The themes within the Centre are:
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Musculoskeletal Ageing mechanisms
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Neuromuscular Ageing
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Interventions for Musculoskeletal Health
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Systems Biology of Ageing
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Motivation for Lifestyle Change
Nutrition features within all themes but especially in the Musculoskeletal Ageing and Interventions themes. For example, Centre researchers Professor Anton Wagenmakers and Professor Paul Greenhaff (Nottingham University) have established that older adults are less efficient in maintaining muscle tissue in part because muscle protein synthesis is compromised, termed “anabolic blunting”. Current research includes determining effects of varying the frequency and quantities of feeding to overcome anabolic blunting, and developing feeding strategies to implement this at population level.
Subcutaneous and visceral adipose tissue increases with age leading to hypertriglyceridemia and elevated inflammatory cytokines and adipokines, which contribute to skeletal muscle insulin resistance. Other ongoing research is testing the hypothesis that the size of the fatty acid flux and release of inflammatory cytokines from adipose tissue stores modulate the degree of blunting of anabolic signals. The mechanisms involved are also being investigated. Elevated muscle cytokines (TNFα, IL6) in obese elderly disturb Akt signaling and activate FOXO transcription factors targeting muscle ubiquitin ligases and pyruvate dehydrogenase kinase isoforms, which collectively suppress muscle protein synthesis, increase degradation and carbohydrate oxidation. Centre researchers are testing the hypothesis that age-related hypertriglyceridemia and systemic inflammation drive molecular and cellular mechanisms that accelerate musculoskeletal ageing. In addition Professor Ed Rainger is focussing on how omega 3 fatty acids, which are high in fish oil supplements, influence inflammation in various tissues by effects on immune cell migration and function.
The metabolic benefits of weight loss are well established and there is considerable interest at UoB in the detrimental effects of obesity, including on the musculoskeletal system. This includes research in the Centre for Obesity Research led by Dr Jeremy Tomlinson to determine the impact of structured, supervised weight loss on musculoskeletal mass, function and the molecular adaptation in muscle in overweight elderly subjects. Additional studies are exploring novel uses for L-leucine and its metabolite (HMB; stimulators of mTOR), with the aim of improving anabolic responses to feeding in elderly skeletal muscle.
The role of age-related endocrine changes are also a major research topic within the Centre, as such hormone changes impact upon the anabolic potential of muscle and one in old age. Professor Paul Stewart and Dr Mark Cooper have shown that 11β-HSD1 expression and activity within muscle and bone increases with age, through an inflammatory cytokine driven (NF-kB mediated) pathway, and the consequent cortisol excess contributes to ‘unhealthy’ musculoskeletal ageing and a reduced ability to maintain muscle and bone. In collaboration with pharmaceutical partners, the effect of short-term administration of 11β-HSD1 inhibitors on bone turnover and skeletal muscle function is being assessed. An additional major endocrine change investigated by Professor Lord and Professor Wiebke Arlt is adrenopause, in which production of the androgen DHEA declines from the age of 30 with profound effect on physical and cognitive function as well as immunity. Importantly, DHEA supplementation has benefits for muscle function, as an androgen precursor raising its endogenous production will provide an androgen agonistic signal to improve muscle mass. Ongoing studies are using DHEA supplementation to prevent frailty in older adults after hip fracture.
Finally the recent appointment of Professor Janice Thompson brings expertise in nutritional assessments and interventions in ethnic minority groupings. The ability to assess dietary intake in a culturally sensitive way in different community settings, will broaden the ability of UoB researchers to carry out lifestyle assessments and interventions in our significant ethnic minority populations. Dr Gareth Wallis is another recent appointment with expertise in nutritional supplementation to improve performance in athletes, but who is now using his knowledge to benefit older adults.