Exercise and circulating factors associated with skeletal muscle and bone health in older age

Piasecki, Jessica (2018) Exercise and circulating factors associated with skeletal muscle and bone health in older age. Doctoral thesis (PhD), Manchester Metropolitan University.

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Abstract

Muscle mass declines 1-2% every year after the age of 50 years. Contractile forces by muscle exert strains on bone and influence the bone mass and strength. Not only is age a cause for muscle and bone decline, circulating factors can play a role, aiding the signalling between muscle and bone. Chapter 3 investigates exercise as a way in which we could reduce the loss of whole body bone mineral density (BMD) and muscle mass in older age. Included in this chapter were 38 master sprint runners (28 males, 10 females, mean age 71±7y), 149 master endurance runners (111 males, 38 females, mean age 70±6y) and 59 non-athletic controls (29 males, 30 females, mean age 74±5y). Sprinter hip BMD was 10% and 14% greater than that in endurance runners and controls respectively, but it was difficult to explain this increased BMD by accelerometry or differences in muscle strength. Following on from this, Chapter 4 highlights that there are circulating factors playing a role within the ageing skeleton. Factors dickkopf-1, osteocalcin, osteoprotegrin and sclerostin were identified to be positively associated with whole body bone mineral density in older adults (n=272), with multivariate regression showing body mass index, circulating sclerostin and whole-body lean mass together accounting for 13.8% of the variation with WBMD. To further investigate the circulating factors, statistical modelling was used to identify those which were also associated with whole body lean mass. Tumour necrosis factor alpha (TNF) and osteoprotegrin (OPG) were significantly negatively (r=-0.170, p=0.007) and positively associated (r=0.140, p=0.030), respectively, with whole body lean mass. With multivariate regression showing height and OPG to account for 45% of the WB Lean mass in older adults. These results, combined with Chapter 4, highlighted OPG as a key molecule associated with both bone and muscle during ageing. Using these findings, in Chapter 6 the interactions between TNF and OPG were modelled using human myoblast cells in vitro. From the investigations in vitro it was clear that OPG is capable of enhancing muscular growth and when incubated with TNF the myoblasts are able to secrete OPG, providing a protective mechanisms against TNF. The findings within this thesis can conclude that circulating factors, particularly OPG, are able to interact with muscle and bone and have an influence the decline during ageing. Exercise, particularly, sprinting can help reduce decline in bone health but circulating factors provide a new insight that could help our forever ageing population.