Contrary to the long-held belief, the link between exercise and slower muscle aging is “implausible”, according to new genetic research from the UK.
Jamie Timmons, professor of Systems Biology in the School of Sport, Exercise and Health Sciences at Loughborough University, and colleagues, write about their study, which offers new insights on the aging process in humans, in the 21 March issue of PLOS Genetics.
In a press statement, Timmons explains that their evidence turns many long-held assumptions about aging upside down.
For instance, the UK Centre for Aging Research advises the government that muscle aging is caused by things like insufficient physical activity, says Timmons.
“However, when we look at the changes in human muscle with age, in both people from the UK and the USA, we do not observe physical activity altering the age-related biological changes,” he adds.
He and his colleagues find that response to exercise is highly variable in humans, and that pre-existing gene states can predict how muscles will respond to physical activity.
In their paper they also describe how they identified the biological molecules that may drive the human body’s response to exercise.
The biggest problem with aging is loss of muscle. For some people, exercise results in what Timmons describes as “good functional effects”, but for around 25% of people exercise has no such benefits, because they simply can’t grow muscle.
“In short, a simple link between muscle aging and lack of exercise is not plausible,” he asserts.
For the study, Timmons and colleagues produced a reproducible molecular profile or chemical fingerprint for human muscle aging.
They combined this analysis with extensive data on the effect of exercise training to see how the different chemical fingerprints reacted to endurance training. The aim was to identify the molecular processes predominantly associated with age and not enviroment or lifestyle.
“We were able to identify unique gene pathways associated with human muscle growth and age and were able to conclude that human muscle age-related molecular processes appear distinct from the processes directly regulated by those of physical activity.”
In other words, age has its own influence on muscle, that is separate from that of physical activity.
A good example is one of the most striking findings, the “active rapamycin signature”, which has a signalling pathway known as mTOR.
They found this signature is determined by genes that are almost entirely inactive in people who are able to increase lean muscle mass.
When they tested the effect of 20 weeks of endurance training on a group of volunteers, they found that the ones who gained the most lean tissue mass had “suppressed mTOR signaling over the training period”, something that had not been seen before.
For those whose genes did not suppress the mTOR signaling, it meant that no matter how hard they exercised, it did not stop their muscle aging.
Timmons says he is excited by the findings, and they are now trying to take them further:
“Ideally, we could identify a drug that slows down the rate of the aging process for use in people who suffer rapid aging, especially in those people who are unable to build muscle tissue with exercise training,” says Timmons.
He explains that there have been attempts before to find genes that control aging in humans, but those studies relied on a classical approach, DNA sequencing.
He and his team took a different approach, they measured the variation in the chemicals that the genes produce.
“In this way we are able to capture the relevant features more easily and with far less cost,” he adds.
The discovery of a chemical signature of human muscle aging that can be reproduced, means that drug screening now has a valid benchmark to aim for rather than just a theory.
But Timmons says their findings rule out “many of these old ideas”.
He and his colleagues anticipate their study will meet with a mixed reaction: some sceptics might see it as challenging their pre-clinical models, and others like the biotech industry, may welcome it more openly and likely to want to take it further.
It is interesting to contrast these findings with those of say the researchers who found exercise may protect aging brains.
Written by Catharine Paddock PhD