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Understanding the effects of ageing on human skeletal muscle autophagy: Combining novel in vitro and ex vivo approaches
Secondary Supervisor(s): Prof Sarah Aldred
University of Registration: University of Birmingham
BBSRC Research Themes:
Project Outline
Ageing is associated with a progressive loss of skeletal muscle size, strength and function, coined sarcopenia, which is ultimately associated with increased mortality. Autophagy, a process facilitating the degradation of damaged/dysfunctional cellular material has recently begun to receive attention for its role in muscle mass maintenance. Despite being inherently catabolic, inhibiting autophagy in animal models leads to muscle atrophy and reductions in force production. Importantly, there is very little evidence regarding the effects of ageing on autophagy in human skeletal muscle, although we have observed a reduced ability to upregulate autophagic flux in vitro in immortalised muscle cells from an older donor. Our group has also recently optimised an ex vivo technique to assess autophagic flux in human muscle – historically ethically challenging to undertake in vivo.
Therefore, the overall aim of this studentship is to comprehensively study the effects of ageing on skeletal muscle autophagy using in vitro and ex vivo methodologies and will consist of 3 experimental objectives:
1. Characterise autophagic flux in skeletal muscle samples from older and younger participants using our novel ex vivo autophagic flux assay.
2. Compare autophagic flux in primary human muscle cells isolated from younger and older donors to those derived in objective 1 – This could allow the generation of an in vitro model to study potential interventions prior to in vivo application.
3. Determine if the age-related systemic environment influences skeletal muscle autophagy by applying younger or older serum to immortalised human muscle cells – Collectively this planned programme of research will deliver a significant training opportunity in novel methodologies to better understand a vital cellular process’ role in age-related skeletal muscle dysfunction.
