LYSOTRACK-ageing
Research type
Research Study
Full title
Defining the role of lysosomal movement in age-associated anabolic resistance in human skeletal muscle
IRAS ID
216684
Contact name
William Apro
Contact email
Sponsor organisation
University of Birmingham
Clinicaltrials.gov Identifier
Duration of Study in the UK
0 years, 9 months, 17 days
Research summary
Age-associated loss of muscle mass, termed sarcopenia, is strongly associated with functional impairment and physical disability in the elderly. Maintenance or growth of muscle mass is mainly driven by increased muscle protein synthesis (i.e. the generation of new muscle protein) in response to exercise and feeding. However, several investigations have shown that elderly individuals have a blunted protein synthetic response following protein intake. This inability of the elderly to properly respond to growth stimuli has been termed anabolic resistance and plays a significant role in the development of sarcopenia. However, the precise mechanisms underpinning anabolic resistance are unknown.
It is well established that muscle protein synthesis at the molecular level is regulated by a cellular protein complex called mTORC1. When exposed to a growth stimulus, mTORC1 has been shown to associate with lysosomes, i.e. the intracellular organelles responsible for the breakdown of cellular proteins, and subsequently moving towards the cell periphery.
This movement of lysosome-associated mTORC1 within the cell is believed to be vital for the activation of protein synthesis, as inhibition of lysosomal movement blunts mTORC1 activation in response to amino acids. Thus, dysregulation of lysosomal movement in ageing muscle may represent an underlying mechanism in the development of anabolic resistance. However, this area of research is unexplored in the context of human skeletal muscle.
Therefore, the aim of this project is to examine the involvement of lysosomal movement in the regulation of protein synthesis in young and old skeletal muscle following resistance exercise and amino acid intake. We hypothesize that dysregulation of lysosomal movement plays a central role in the development of age-associated skeletal muscle anabolic resistance. This project has the potential provide novel insights into the age-associated dysregulation of protein synthesis and stimulate the development of life quality-enhancing treatments for the ageing population of the UK.REC name
West Midlands - Black Country Research Ethics Committee
REC reference
17/WM/0068
Date of REC Opinion
22 Mar 2017
REC opinion
Further Information Favourable Opinion