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Title: Establishment of a functional musculoskeletal test system in mice to determine the effects of possible interventions on age-related musculoskeletal dysfunction
Author: Nye, G.
ISNI:       0000 0004 6495 9501
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2017
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The age-related loss of skeletal muscle mass and function is a key contributor to physical frailty in older individuals. In addition to this, the increased development of bone and joint disorders such as osteoporosis and osteoarthritis with ageing present a complex problem. Current understanding of the mechanisms responsible for age-related musculoskeletal deterioration is poor. The overall aims of this study were to integrate methods of measuring and visualising age-related changes in musculoskeletal tissues in a mouse model of ageing and to test a range of differing potential interventions known to protect individual tissues during ageing on the whole musculoskeletal system. Data demonstrated that C57Bl6 mice are a reliable model to study ageing, particularly in muscle and bone (Muscle mass reduced by ~40% and trabecular bone halved between 3 and 28 months of age); however these mice did not demonstrate evidence of any gross changes in the hind limb joints or tendons. C57Bl/6 mice were supplemented dietary sodium nitrate for either a short (18-24 months old) or longer (9 to 24 months old) to determine whether supplementation at key stages of development of musculoskeletal tissue dysfunction would result in preservation of muscle or bone without the need for more invasive treatment. No significant differences were reported in the long term treatment, however short-term treatments of mice with nitrate resulted in a significant decrease in muscle mass and function and this was associated with changes in trabecular bone disputing our initial hypothesis. HSP10 overexpression in muscles of mice has been shown to preserve muscle force generation and cross-sectional area in old mice previously. As proof of principle, the direct effect of such preservation of muscle on bone was tested. Preservation of muscle was evident as in the previous study; however, little effect of this was seen on bone disputing the dominant role the muscle has over bone tissue. A cohort of wild mice was then used to challenge the widely used Bl/6 mouse model and demonstrated substantial spontaneous deterioration of joint tissues as well as increased loss of muscle and bone tissue compared to the Bl/6 mice. These results indicated a possible altered ageing process in the lab bred C57Bl/6 mouse which may impact the research using them.
Supervisor: McArdle, A. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral