Muscle architectural and physiological responses to immobilisation: impact of age and obesity

Ali, Arfan M. (2020) Muscle architectural and physiological responses to immobilisation: impact of age and obesity. PhD thesis, University of Nottingham.

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Clinical scenarios of recovery from illness or injury both require acute, mandatory periods of bed rest or immobilisation. However, this inevitably leads to; muscle loss, muscle weakness and a number of negative health problems which may be exacerbated in the elderly and in the obese. Both ageing and obesity are accompanied by reduced habitual physical activity levels and impaired muscle metabolic health which may pose an additive burden on musculoskeletal health in these patients. Therefore, understanding musculoskeletal deterioration associated with immobilisation is a major public health issue and embodies a vital area for scientific investigation.

This thesis describes a series of human volunteer studies performed to elucidate the short-term (3 days) and longer-term (14 days) impact of muscle unloading on muscle metabolic and physiological health in healthy young and older, normal weight and obese volunteers

The major findings were: 3 days of unilateral lower limb immobilisation in healthy normal weight young and older volunteers supressed myofibrillar protein FSR by ~25% (p<0.01) and ~22% (P<0.05) respectively when compared to the non-immobilised limb at baseline, whilst this was not apparent in healthy young obese volunteers. In addition, ultrasonography-determined medial gastrocnemius muscle volume declined during immobilisation in the young normal weight group and the young obese group by ~7% (p<0.05) and ~15% (p<0.01) respectively, but not the older normal weight group. A significant association was observed between ultrasonography and MRI determined baseline muscle volume (medial gastrocnemius and vastus lateralis) and the absolute decline in muscle volume during unloading across all age groups and BMI ranges. Finally, 14 days of bed rest initiated similar changes in targeted mRNA expression during bed rest from which IPA analysis predicted similar changes in cellular functions in young and older humans, whilst 14 days of exercise rehabilitation in older humans resulted in an attenuated response in mRNA expression from which IPA analysis predicted a differential response in cellular functions relating to muscle differentiation and lipid metabolism.

This thesis has provided novel insight regarding changes in muscle architecture and protein metabolism in response to short-term muscle unloading in humans and further impacts of aging and obesity on these parameters. In addition, this thesis has provided novel insight regarding mRNA gene expression changes during longer-term bed rest in young and older volunteers and during rehabilitation and has offered insight of metabolic functions most affected by these changes. These findings have important implications for the development of nutritional and exercise strategies to attenuate muscle atrophy during muscle unloading.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Scammell, Brigitte E.
Greenhaff, Paul L.
Keywords: human muscle unloading, human muscle disuse atrophy, muscle immobilisation, muscle protein synthesis, D2O
Subjects: W Medicine and related subjects (NLM Classification) > WE Muscoskeletal system
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID: 60396
Depositing User: Ali, Arfan
Date Deposited: 17 Jul 2020 04:40
Last Modified: 17 Jul 2020 04:40

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