We’ve always known that exercise is good for us. But a new study is adding a fascinating layer of detail to that story — one that plays out not in our muscles or lungs, but in our DNA.
Exercise and physical fitness has been shown to reduce the predicted biological age generated by various epigenetic clocks. These clocks work by measuring patterns of DNA methylation — chemical tags on our genes that shift predictably as we age — and use them to estimate how old our bodies actually are on a biological level, independent of our birth certificates. A new study of 936 participants in the U.S. population takes this a step further by asking why exercise has this effect, and points to a compelling culprit: inflammation.
β2-microglobulin (β2M) is elevated in states of chronic inflammation and is implicated in immune senescence. Elevated levels are detected in the plasma and cerebrospinal fluid of aged mice and older adults. Think of β2M as a molecular alarm bell — when it’s ringing loudly and constantly, it’s a sign that the immune system is in a state of smoldering, low-grade overdrive. That kind of chronic inflammation, sometimes called “inflammaging,” is one of the more insidious features of getting older, quietly degrading tissue and accelerating disease.
The study’s key finding is that exercise appears to quiet that alarm. Increased physical activity was significantly associated with lower β2M levels, and mediation analysis revealed that reductions in β2M explained 37.67% of the association between physical activity and biological age. In other words, more than a third of exercise’s anti-aging benefit on epigenetic clocks can be attributed specifically to its ability to tamp down inflammatory signaling.
But that still leaves nearly two-thirds of the effect unexplained — which is, if anything, the more intriguing part. The direct effect of physical activity on biological age remained significant even after accounting for β2M, suggesting additional pathways through which exercise exerts anti-aging effects, such as epigenetic regulation or mitochondrial function.
The practical takeaway is both simple and profound: regular physical activity doesn’t just make you feel younger — it appears to make you biologically younger, through multiple mechanisms we’re only beginning to map. For a field that sometimes gets lost in the complexity of longevity science, this is a reassuring reminder that one of the most powerful tools we have is also one of the oldest. You don’t need a pill or a clinical trial. You just need to move.
