Epigenetics of Age-Related Muscle Wasting
Research type
Research Study
Full title
Genome-Wide Epigenetics of Skeletal Muscle Wasting in Elderly Patients
IRAS ID
239402
Contact name
Adam Philip Sharples
Contact email
Sponsor organisation
Keele University
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Maintenance of skeletal muscle mass is fundamental to enable healthy ageing. Muscle wasting occurs following injury, immobilisation/disuse and surgery in elderly populations contributing to earlier morbidity and mortality. Recently, work from our group has suggested an important role for epigenetics, particularly DNA methylation, in muscle wasting after disuse-atrophy in rodents (Fisher et al., FASEB J 2017), and recently published data (Seaborne et al., Scientific Reports 2018) demonstrates extensive alterations in genome-wide DNA methylation after muscle growth in humans. Finally, others have suggested the accumulation of DNA methylation strongly contributes to ageing in several tissues. We aim to investigate genome-wide DNA methylation (850,000 sites in the DNA) in skeletal muscle wasting that occurs following immobilisation and surgery in elderly patients. Skeletal muscle tissue will be derived and muscle stem cells isolated from 20 patients (aged ≥ 65) who have been immobile prior to knee/hip surgery (e.g. due to a fall), 20 aged-matched patients who are not immobile (typically undergoing elective surgery) and 20 young (18-35 years) healthy adults. Genome-wide DNA methylation and targeted gene expression will be assessed in the wasting skeletal muscle tissue versus controls using latest technologies (Methylaton via Infinium MethylationEPIC BeadChip arrays). Bioinformatical analysis of ‘large-data’ will be undertaken using Partek Genomics software downloaded onto the chief investigators and the PhD student/researchers password protected laptop. Identification of novel epigenetically regulated genes (methylation) will be mapped against genes that are turned on/off. This will provide crucial understanding of the mechanisms underlying muscle wasting in elderly patients. Further, muscle stem cells will be used to create bioengineered ‘mini-muscles’ of the human patients in-vitro. This will enable future follow on funding to develop a relevant human in-vitro model of aged muscle wasting to therapeutically target the genes identified above using drugs or gene therapies, prior to moving to clinical trials.
REC name
West Midlands - Black Country Research Ethics Committee
REC reference
18/WM/0187
Date of REC Opinion
7 Aug 2018
REC opinion
Further Information Favourable Opinion