Welcome to our research group studying the role of RNAs in muscle ageing and disease

Irreversible muscle loss and weakness are a growing issue of our ageing population with substantial socio-economic burden on European health services that will increase without the development of effective therapies. There are currently no treatments to target muscle loss despite the significant health and social issues associated with it.
Sarcopenia (age-related muscle loss), amyotrophic lateral sclerosis (a progressive disease associated with motor neuron degeneration and muscle loss) and cachexia (a progressive wasting syndrome) are multifactorial conditions, sharing several common mechanisms associated with muscle wasting, hospitalisation and decreased lifespan. microRNAs (miRNAs), potent regulators of gene expression, provide an attractive alternative strategy against muscle loss due to their simultaneous regulation of multiple gene expression without safety issues.
Using state-of-the-art omics approaches and discovery-driven bioinformatic tools, we will establish a set of conserved key miRNAs, fit-miRs, commonly dysregulated in muscle in ageing and disease.  Functional studies in complementary models of in vitro and in vivo muscle loss will validate the crucial role of fit-miRs in muscle homeostasis and their potential to improve muscle mass and strength in ageing and disease.

Loss of skeletal muscle mass and strength with age is one of the primary underlying causes of hospitalisation and bed rest. Currently there is no effective treatment although resistance exercise has proved to delay its onset. Understanding the underlying cellular changes is essential for designing an effective therapy. Key regulatory molecules that control the level of expression of proteins within the muscle are called microRNAs. However, these molecules can be targeted by other molecules generated within the cell such as ROS. Modification of microRNAs can result in a loss of specificity for their targets and pathogenesis. A vicious cycle occurs during ageing with a dysregulation of miRNAs, resulting in aberrant protein regulation and muscle wasting.

Approximately 58% of those hospitalised in Ireland are aged >65 and many require ICU. Ventilator-induced diaphragm dysfunction (VIDD) and muscle wasting are found in critically ill patients within 24 hours of initiation of mechanical ventilation and can persist beyond 12 months.

Elevated cytokine levels, immunosenescence and muscle weakness are common in older people. COVID-19 patients with severe ARDS show increased IL6 levels and macrophage activation and are often administered drugs inducing muscle relaxation during ventilation, further increasing risk of muscle wasting in survivors.

Therefore, COVID-19 critical illness, especially in older people, is likely to lead to premature frailty and long-term disability, loss of independence, further hospitalisation and increased morbidity and mortality. There is no effective treatment for muscle wasting. Muscle loss leading to frailty is an increasing socio-economic and healthcare challenge in our ageing population and is likely to become a public health priority in the light of the current pandemic. 

In this HRB-funded project, we are investigating whether microRNAs, small molecules which regulate the function of our cells, can predict or improve muscle health and strength following critical illness such as COVID-19.

The project is a collaboration with NUI Galway’s Dr Brian McDonagh and Professor John Laffey, Dr Bairbre McNicholas of University Hospital Galway, Professor Ken O'Halloran from UCC and Dr Rónán O’Caoimh from Mercy University Hospital Cork. 

https://spark.adobe.com/page/JONV1RIhHlBAF/

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