Understanding the cross-talk between innate immune cells, skeletal muscle and adipose tissue and how this is altered with ageing and obesity?

Ageing is associated with a progressive decline in skeletal muscle mass (sarcopenia) and an associated increase in adiposity, leading to increased levels of inflammatory cytokines. Importantly, ageing is also associated with a decline in the innate immune function, known as immunosenescence. Importantly, recent studies have suggested that cross-talk exists between innate immune cells and skeletal muscle and adipose tissue which may mediate sarcopenia and immunosenesence.

It is known that skeletal muscle contains a population of resident immune cells, and additional immune cells infiltrate skeletal muscle in ageing individuals who develop obesity and type II diabetes (inflammaging), where they can secrete numerous growth factors and cytokines which are candidate mediators of skeletal muscle regeneration and remodelling (2). In turn, sarcopenia and the increase in adiposity with ageing alters the expression of adipokines and myokines, for example secretion of IL-15, which impact on innate immune cell functionality, in particular Natural Killer cells (3). Furthermore, the prevalence of sarcopenia is greater in obese older individuals (4), where it is associated with a greater inflammatory burden and therefore we also expect these age-related changes in immune function to be exacerbated in sarcopenic obesity.

We hypothesise that pathological cross-talk between innate immune cells, skeletal muscle and adipose tissue with ageing drives sarcopenia and immunosenescence and this is exacerbated in elderly patients who are obese.

The aims of this proposal are therefore to examine the cross-talk signalling pathways between immune cell function, skeletal muscle and adipose tissue and determine how this is altered with ageing and in individuals who are obese. To do this we will collect blood samples from elderly and young adults who are either obese or lean. The profile of innate immune cells with regards cell numbers, immune cell function and production of relevant growth factors and cytokines will be assessed.

We will then explore the cross-talk signalling between young vs old innate immune cells and skeletal muscle and adipose tissue. In brief, these studies will examine the effect of growth factors and cytokines from different innate immune cell populations on primary skeletal muscle cell proliferation, differentiation (MyoD and myogenin) and the expression of known muscle anabolic and catabolic mediators (calpains, E3 ligases). In turn, we will examine the effect of muscle and adipose secreted cytokines/myokines on the function of innate immune cells.

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