Study reveals how muscle cells deteriorate with age, hampering injury recovery

Researchers have revealed how muscle cells deteriorate with age, affecting their ability to regenerate and recover after an injury. The findings could help to shed light on why it takes people longer to recover from muscle damage as they age. A team at Nottingham Trent University analysed the genes inside muscle cells, and found the ‘development pathways’ – the different ways in which genes work together to regenerate muscle – become weakened in older cells. We know that healthy muscle regenerates after we’ve had an injury but ageing impairs that regeneration potential and recovery gets harder the older we get Dr Livia Santos, Nottingham Trent University Lead researcher Dr Livia Santos, an expert in musculoskeletal biology in Nottingham Trent University’s School of Science and Technology, said: “This goes some way towards explaining why muscle injuries may take longer to recover as we get older.” She added: “We know that healthy muscle regenerates after we’ve had an injury but ageing impairs that regeneration potential and recovery gets harder the older we get. “What we’ve observed, in terms of what happens inside the cells, helps us to better understand why we don’t heal as well or as quickly in older age. “The pathways that control cell processes and development work differently in older cells and are downregulated, meaning regeneration is impacted the older we get. “If we can understand these pathways, however, we could potentially identify new therapies and interventions to mitigate the problem.” The researchers developed a new approach to examine muscle cells in the laboratory to enable them to observe the different mechanisms that drive muscle ageing. They studied muscle cells from donors, chemically injuring cells after they had been donated and isolated, then assessing how they heal and regenerate back to their pre-injury baseline levels. When they looked at cells from a 20-year-old and a 68-year-old donor, researchers found distinct differences in the development pathways of the younger and older cells. While younger muscle cells fully recovered from the injury, the team found that in older cells the genes expressed less of what they needed to, leaving the cells no longer able to perform in the way they should. According to the researchers, this contributes to reduced regeneration capacity leading to thinner, less robust ‘myotubes’ – a type of cell that can fully develop into a muscle fibre. Muscle regeneration is a complex and finely balanced biological process and is known to deteriorate with ageing, leading to the decline of musculoskeletal health and in some cases metabolic and genetic diseases. Our work enables us to examine muscle cell regeneration across the lifespan and this in turn could be key for future drug discovery for disease related to muscle ageing Researcher Janelle Tarum Janelle Tarum, another researcher on the study, said: “We’ve been able to develop a new approach to assess muscle regeneration which involves a state-of-the-art technique called RNA-sequencing. “There’s a very clear reduced regeneration capacity and weakened recovery of aged cells and we have been able to further understand the factors underlying this impairment. “Our work enables us to examine muscle cell regeneration across the lifespan and this in turn could be key for future drug discovery for disease related to muscle ageing.” The study, which also involved Manchester Metropolitan University and Liverpool John Moores University, is published in the Journal of Tissue Engineering and Regenerative Medicine.