New research by York University kinesiologists is advancing our understanding of why our muscles shrink when we don’t use them.
Michael O’Leary, a doctoral student in York’s School of Kinesiology & Health Science, found that a week of total muscular disuse – such as experienced after a serious injury – can cause 24 per cent muscle loss. The research was conducted in the Faculty of Health’s new Muscle Health Research Centre, which is the first of its kind in North America.
"It really is a case of use it or lose it," he says. "We’re seeing more and more evidence of how easy it is to lose muscle, compared to how difficult it is to regain it." O’Leary conducted his research under the supervision of David Hood, Canada Research Chair in Cellular Physiology and a professor in the School of Kinesiology & Health Science in York’s Faculty of Health.
During chronic muscle disuse, a process called autophagy (or type two cell death), works in tandem with apoptosis (or type one cell death), attacking cells and causing muscles to shrink.
O’Leary measured significant increases in the proteins LC3 and Beclin 1 as a result of this process. Beclin 1 is a known tumour suppressor and is found at lower levels in several types of cancer cells. Seven days of muscle inactivity caused levels of Beclin 1 to increase threefold.
The proteins are activated by a decrease in oxygen consumption by the mitochondria, which supply power to our cells, leading to an increase in tiny molecules called reactive oxygen species. Free radicals – implicated in conditions ranging from cancer to wrinkles – are a common type of such molecules. In high doses, they wreak havoc on cells by activating the production of these proteins, which in turn activate the pathways to cell death.
O’Leary also observed heightened levels of LC3 in mitochondrial membranes, offering evidence that autophagy may specifically target and degrade mitochondria.
Eventually, researchers hope to discover how to lessen or even prevent this damage.
"We’re trying to understand how autophagy might possibly mediate the process of muscle atrophy," says O’Leary. "It’s especially important, considering the tendency in North America towards sedentary lifestyles and an overall decrease in physical activity."
"Denervation-induced oxidative stress and autophagy signaling in muscle," was published in the journal Autophagy on Feb. 16. It was co-authored by Hood.