The Vitamin D receptor and musculoskeletal ageing: a multi-modal approach

Lead Research Organisation: University of Nottingham
Department Name: School of Medicine


Vitamin D deficiency is highly-prevalent and has been linked - mainly through population epidemiology - to musculoskeletal (MSK) decline in both ageing, and age-related diseases. Nonetheless, mechanistic links between Vitamin D deficiency and MSK health remain poorly defined. Vitamin D exerts many of its cellular actions through the vitamin D receptor (VDR). We have recently found that loss-of-function and gain-of-function of the VDR stimulated skeletal muscle atrophy and hypertrophy, respectively, in rat electroporation models. These data add to, and further, evidence from transgenic models of VDR knockout (KO) illustrating that the VDR regulates skeletal muscle mass. Moreover, in the same study, we showed that VDR expression was reduced in older humans, while expression of the VDR increases in line with muscle mass gains in response to resistance exercise. Collectively, all available data suggest Vitamin D and Vitamin D receptor dependent regulation of muscle mass (our data, autonomously so).

Vitamin D-deficiency and altered VDR regulation has been implicated in MSK ageing and many age-related diseases. This maybe for many reasons e.g. poor diet, reduced sunlight exposure and deranged processing of Vitamin D molecules to bio-active receptor binding steroid forms (in addition to age-related dysregulation of VDR gene expression). However, follow-on research is needed to define links between Vitamin D status, VDR and MSK health. The present project will; 1) identify novel links between Vitamin D status and MSK ageing, using existing ageing/exercise/immobilization/COPD bio-banks; 2) determine Vitamin D, and Vitamin D-independent effects on muscle mass using a pre-existing cell model of VDR knockdown (lentivirus-mediated sustained VDR loss-of-function previously generated and sustained, in the host-lab); 3) determine if Vitamin D deficiency leads to exercise maladaptation(s).


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Studentship Projects

Project Reference Relationship Related To Start End Student Name
MR/R502364/1 30/09/2017 29/06/2023
2276104 Studentship MR/R502364/1 30/09/2019 04/06/2023