Dissertation

The Role of Genetic Variation in Selected Human Musculoskeletal Ageing Traits

Jones, Garan

2021

نظرة عامة

Loss of muscle mass and function, termed sarcopenia, occurs commonly with advancing age. This loss of strength can have a profound impacts on an individual’s life expectancy and quality of life. Population genetic studies can provide information on underlying biological mechanisms, but little was known about the genetic contributions to sarcopenia.By using data from multi-national community based studies of 256,523 individuals of European ancestry aged 60 years or older I have identified 15 genomic risk loci for muscle weakness with age. I have shown that the genetic contributions to muscle weakness in later life have novel characteristics not seen in studies of muscle strength at younger ages. I have also shown that for a section of the older population meeting the criteria for sarcopenia, there is a substantial auto-immune component separate from diagnosed autoimmune conditions, such as Rheumatoid arthritis. Analysis of sex-specific cohorts has highlighted that the underlying genetics contributing to muscle weakness with age differ between the sexes. Additional research on the shared pathways between age-related traits and muscle weakness with age has shown that diabetes, rheumatoid arthritis and life courses traits, for example birth weight, share at least some of the same biological pathways. Biological pathways implicated included transcription regulation, processing of misfolded proteins, cell growth and development.In conclusion I have identified several common genetic variants associated with sarcopenia in humans, which has highlighted an autoimmune component and several shared casual pathways with traits ranging from life-course and growth traits through to later life conditions such as Rheumatoid arthritis and diabetes. These findings should inform efforts to prevent and treat muscle loss with advancing age, and may more personalised approaches to intervention.

• الناشر: ProQuest Dissertations & Theses
• موضوع: Aging / Arthritis / Body mass index / Frailty / Gerontology / Health sciences / Magnetic resonance imaging / Medical imaging / Medicine / Mortality / Older people / Public health / Womens health
• ISBN: 9798379636807