Stepping Back in Time: Weighted Endurance Exercise Program Reduces Biological Age of Older Mice By 10%

We all know that exercise is beneficial to our bodies and minds, strengthening everything from our heart to our muscles to our brain. But can exercise actually turn back the clock and make us younger? A new study suggests that this may be the case, showing how a combination of resistance and endurance exercise takes 10% off the biological age of older mice.  

Unlike the chronological age that reflects the date on your birth certificate, biological age assesses how old your cells, organs, and tissues are. While these two tend to line up during our younger years, they can drift further and further apart as we grow older. With a biological age greater than your chronological one, you’re more likely to experience accelerated aging and disease onset. Conversely, healthy habits can keep you biologically young regardless of how many birthday candles you have. In this recent study published in Aging Cell, Murach and colleagues show how late-life physical activity does, in fact, turn back the clock — even when the mice were sedentary for most of their lives — showing that it’s never too late to reap the youth-inducing benefits of exercise.

Muscles, Mice, and Methylation

Over the past decade or so, many longevity researchers have made it their mission to determine the best way to quantify biological aging — and how to slow it down or even reverse it. One such method is looking at the changes that occur to our DNA. A common form of DNA modification is methylation, the addition or removal of chemicals called methyl groups to strands of DNA. Methylation doesn’t change the DNA sequence itself but, instead, alters how our cells read the genes — also known as epigenetic changes. Although methylation in itself is neither good nor bad, as both over- and under-methylation can be harmful, aging or leading an unhealthy lifestyle can cause hypermethylation on too many DNA strands. 

By assembling a large dataset of sites where DNA methylation changes typically occur with age, these biological clocks can predict with impressive precision how fast you are aging on the inside. As the co-first author of this study, Kevin Murach, an assistant professor in the Department of Health, Human Performance and Recreation at the University of Arkansas, explains, “DNA methylation changes in a lifespan tend to happen in a somewhat systematic fashion, to the point [that] you can look at someone’s DNA from a given tissue sample and, with a fair degree of accuracy, predict their chronological age.”

In this study, Murach and colleagues focused on aging and methylation within the skeletal muscle of aged mice. While previous research has found that exercise alters muscle DNA methylation, it’s been unclear whether or not exercise can turn back the biological clock to a younger age through these methylation changes. 

Weighted Endurance Exercise Blunts Biological Age

To test the effects of exercise on internal aging, the Arkansas-based research team allowed 22-month-old mice (about 60 in human years) access to a weighted exercise wheel. Unlike a typical treadmill-style wheel, the extra weight enabled muscle growth. While there isn’t an exact replica for human exercise, the authors compare it to walking with a heavy backpack for many miles.

After two months of this progressive weighted wheel running, the 24-month-old mice (now 70 in human years) showed epigenetic ages of mice eight weeks younger than sedentary older mice of the same age. Although that doesn’t seem like much, the 8-week decrease in biological age is equivalent to roughly 10% of a mouse’s lifespan. This could correlate to almost eight years biologically younger in an American with an average lifespan of 79 years — not insignificant!

Before starting the exercise program, older mice had over seven times more hypermethylated sites than young mice. After the 2-month study, they saw a significant shift toward more youthful methylation levels in many of these sites. Some of the genes that had these beneficial shifts included those related to the structure and activity of our cells’ energy hubs (the mitochondria), energy production, and regulation of a protein that controls muscle weight and function. 

Making Moves on Methylation

While the results are impressive, Murach and colleagues are not yet prepared to say definitively that the reversal of methylation with exercise can cause improved muscle health — for now, the results solely show a reduction in epigenetic age. As Murach explains, “That’s not what the study was set up to do.” However, the research team plans to keep studying this topic to determine if reductions in DNA methylation do alter muscle function, which could prove highly beneficial to the millions of older adults who suffer from muscle-related physical decline.  

Some emerging questions that the team aims to explore next include, “Do changes on these very specific methylation sites have an actual phenotype that emerges from that? Is it what's causing aging, or is it just associated with it? Is it just something that happens in concert with various other things happening during the aging process? So that's what we don't know.” Future research will need to uncover the answers to these questions, but for now, (safely) hopping on a treadmill or walking trail wearing a weighted backpack likely has no downsides — and may even make your cells younger, too. 

References:

Murach KA, Dimet-Wiley AL, Wen Y, et al. Late-life exercise mitigates skeletal muscle epigenetic aging. Aging Cell. 2022;21(1):e13527. doi:10.1111/acel.13527