Research to Date
As we get older we see reductions in important growth factors (such as the IGFs) and increases in inflammation (such as cytokine TNF-alpha) in both the circulation and that locally secreted by skeletal muscle. These changes have been strongly associated with the acceleration and therefore progression of age-related muscle wasting (sarcopenia). We have published extensively on the role of growth factors, particularly IGF-I and associated signalling, (see papers: 1 , 2 , 3 , 4, 5, 6, 7, 8, 9, 10, 11, 12, 13) and inflammatory cytokines such as TNF-alpha (see papers 1, 2, 3, 4, 5, 6, 7) in muscle cell regeneration and degeneration in order to model ageing, inflamed muscle wasting and caloric restriction in skeletal muscle cells in-vitro. In these papers we have also manipulated the molecular response, both pharmacologically and nutritionally, in attempt to reverse some of the impairments in the regulation of IGF’s and TNF-alpha with age.
Image above: Muscle wasting occurs with age with an increase in inflammation (e.g. TNF-alpha levels) and decreases in growth factors (e.g. IGF-I levels)
Important achievements in this area include:
- David C. Hughes (when completing his PhD in the Sharples Muscle Lab), defined an important role for the activation of the testosterone-AR pathway that partially reversed an ageing phenotype in skeletal muscle cells (See Link 1; Link 2).
- We were the first internationally to characterise the role of the protein, IGF-I binding protein-2 and downstream PTEN/Akt signalling in muscle cell regeneration (Sharples et al., 2013).
- Finally, we published a review article on skeletal muscle growth factors and cytokines and their role in life/health-span in top international journal Aging Cell (Click for PDF) that received the award for the most accessed article in the journal that year (2015) and has had over 100 citations to date (Sept 2019).
Current / Future Research Focus
Image above: Resveratrol (found in the skin of red grapes) chemical structure.
In collaboration with synthetic chemist Dr Chris Coxon (LJMU, UK) we are currently investigating the role of novel resveratrol analogues in skeletal muscle cells. Resveratrol is a polyphenol derived from the skin of red grapes and has been associated with lifespan extension in animal models. Early work Led by Professor Claire Stewart and collaboration with Dr. Amarjit Saini (Karolinska Institute), identified that resveratrol could help protect muscle from inflamed muscle wasting in-vitro (link). The Sharples Muscle lab have since identified that resveratrol can prevent muscle wasting as a result of glucose restriction in-vitro (link). However, its impact is not long lasting. We are therefore investigating the role of these novel resveratrol analogues in regulating an important epigenetic modifier, histone deacetylase SIRT1, and its cross talk with IGF and TNF-alpha signalling in muscle wasting in-vitro, in an attempt to optimise and extend the positive benefits of resveratrol.