Investigating mechanisms of mitochondrial quality control within skeletal muscle across healthspan

The UK is in the midst of a period of rapid demographic change. For example, by 2040, nearly one in four people in the UK (24.2%) will be aged 65 or over. This sub-population already demand substantial medical and social care, a characteristic partly explained by the fact that healthy life expectancy of individuals living in England is 65 years. To avoid overwhelming the NHS over the next decade, it is vital that healthy life expectancy increases significantly. Taken together, these data highlight the immediate need to: i) further our understanding of the dysregulatory molecular mechanisms that impair the cellular machinery vital for healthy ageing and; ii) develop therapeutic strategies that target molecular dysregulation in order to increase healthspan.
Mitochondria, an organelle integral to cellular ATP resynthesis and therefore, skeletal muscle function, have been the target of much research in the context of healthy ageing. To this end, age associated mitochondrial dysfunction has been well studied as a candidate mechanism underpinning the decline in physical capacity that manifests in ageing. Although evidence demonstrating impaired mitochondrial function with increasing chronological age is equivocal, there is a need to elucidate alternative molecular mechanisms that may help explain sarcopenia and age related loss of physical function.
There is evidence to suggest skeletal muscle mitochondrial quality control, or in other words, the restoration and clearance of damaged mitochondria is impaired with increasing age. As molecular processes regulating mitochondrial quality control, rodent data indicates mitochondria specific autophagy (mitophagy) as well as mitochondrial fusion and fission events (mitochondrial dynamics) within skeletal muscle to undergo age induced dysregulation.
This project will explore possible age induced changes and therapeutic strategies to augment mechanisms of skeletal muscle mitochondrial quality control in both cell and human models.