CMAR

Theme one

Mechanisms of musculoskeletal ageing

This theme aims to increase the understanding of the mechanistic basis of age-related musculoskeletal decline and the factors modulating this trajectory, including cell senescence, inflammation, metabolism, physical inactivity and sedentariness, obesity, nutrition and the gut microbiome

The mechanisms underlying anabolic resistance with age are a major interest in the Centre

  • Professor Atherton and Professor Ken Smith use stable isotope tracers and deuterated water to quantify protein and substrate turnover in acute and chronic intervention studies in older people to understand better the aetiology and drivers of anabolic resistance, including a focus on insulin resistance;
  •  Use of tracer approaches combined with metabolomics (with Professor Rick Dunn at Birmingham and Dr Dan Wilkinson at Nottingham) to generate non-invasive biomarkers of muscle
    protein synthesis and breakdown in humans, which can then be used in large-scale intervention studies in Theme 3
  • Professors Ian MacDonald and Nate Szewczyk use their access
    to spaceflight research facilities to study the effects of immobilisation on insulin resistance and muscle anabolic responses;
  • Dr Tim Constantin-Teodosiu determines alterations in skeletal muscle intermediary metabolism and associated molecular regulation of anabolic responses;
  • Professor Martin Hewison researches the impact of Vitamin D bioavailability on muscle anabolic responses; 
  • Professor Greenhaff and Dr Leigh Breen are examining the impact of sedentary behaviour and obesity on muscle metabolic quality and the mechanistic determinants;
  • Professor Gareth Lavery is investigating the role of declining NAD+ supply in muscle mitochondrial function with age in humans as supplementation with nicotinamide riboside has been shown to restore NAD+ levels and reduce functional senescence in muscle cells in mice;
  • Professor Janet Lord is determining the processes driving  accumulation of senescent cells with age, specifically involvement of reduced NK cell cytotoxicity towards senescent cells;
  • Professor Chris Miall researches the impact of behavioural  training on neural control of movement with age;
  • Dr Ned Jenkinson researches the impact of age and disease on motor control and movement learning;
  • Dr Raymond Reynolds studies the central mechanisms involved in compensation for age-related vestibular loss and the variability that increases fall risk;
  • Dr Matt Piasecki researches the impact of age on neuromuscular
    junction function.

This theme is led by

Professor Philip Atherton

(University of Nottingham)

and Professor Martin Hewison

(University of Birmingham)

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