Older mice would run anywhere from six to eight kilometres a day, mostly in spurts, while younger mice might run up to 10-12 kilometres. The weighted wheel ensured they built muscle. While there wasn't a direct analogue to most human exercise routines, Murach likened it to "a soldier carrying a heavy backpack many miles."
When the mice were studied after two months of progressive weighted wheel running, it was determined that they were the epigenetic age of mice eight weeks younger than sedentary mice of the same age -- 24 months. Murach noted that while the specific strain of mice and their housing conditions could impact lifespans, "historically, they start dropping off after 24 months at a significant rate." Needless to say, when one's lifespan is measured in months, an extra eight weeks -- roughly 10 per cent of that lifespan - is a noteworthy gain.
The science behind this when complicated, hinged largely on a biological process known as DNA methylation. A recent New York Times article discussing Murach's work on muscle memory described methylation "as a process in which clusters of atoms, called methyl groups, attach themselves to the outside of genes like minuscule barnacles, making the genes more or less likely to turn on and produce particular proteins."
As the body starts ageing, there tends to be increased DNA methylation, or even hypermethylation, at promoter sites on genes in muscle. "DNA methylation changes in a lifespan tend to happen in a somewhat systematic fashion," Murach explained, "to the point you can look at someone's DNA from a given tissue sample and with a fair degree of accuracy predict their chronological age." Due to this, researchers could use one of a number of "methylation clocks" to determine the age of a DNA sample.
While the paper strengthened the case for exercise, there was still much that needed to be learned. Though the connection between methylation and ageing was clear, the connection between methylation and muscle function was less clear. Murach was not yet prepared to say that the reversal of methylation with exercise was causative for improved muscle health. "That's not what the study was set up to do," he explained. However, he intended to pursue future studies to determine if "changes in methylation result in altered muscle function."
"If so, what are the consequences of this?" he continued. "Do changes on these very specific methylation sites have an actual phenotype that emerges from that? Is it what's causingageingg or is it just associated with it? Is it just something that happens in concert with a variety of other things that are happening during the ageing process? So that's what we don't know."