Exercise’s Impact on Cognition, Molecular Aging

By Allison Proffitt

October 8, 2026 | Exercise didn’t sharpen thinking in breast cancer survivors, but it may have slowed their biological clocks according to two papers reporting findings from the I Can! (Improving Cognition After Cancer) trial, run at the University of California, San Diego. Both studies were published on Sept. 30, 2026, in the Journal of the National Cancer Institute.

Cognition, memory, and attention can all suffer after cancer treatment, possibly from a combination of treatment effects, inflammation, hormonal changes, fatigue and stress. The I Can! trial enrolled 253 breast cancer survivors who reported memory or thinking problems and got little exercise. To support the primary research, half received remotely-delivered coaching (bi-weekly to monthly) to build up moderate-to-vigorous physical activity, supported by a Fitbit and regular calls—the exercise arm. The other half got calls on the same schedule, but on healthy-aging topics with no push to exercise—the health and wellness arm.

Researchers tested whether processing speed and self-reported cognition differed between the arms and looked for improvement in attention and memory among patients in the exercise arm (DOI: 10.1093/jnci/djag295). Researchers also looked closer at participants who had given blood samples and explored 124 to see whether exercise changed biological aging measured by DNA methylation—so called “epigenetic clocks” (DOI: 10.1093/jnci/djag296).

A Null Result, A Biological Signal

Researchers found that the exercise program did work as a behavior change, but that change did not yield cognition benefits (DOI: 10.1093/jnci/djag295). Women in the exercise arm added about five minutes a day of moderate-to-vigorous activity, roughly 35 minutes a week more than the comparison group and sustained it through 12 months. But that behavioral change didn’t impact processing speed and self-reported cognition, the primary endpoints of the study. Both arms improved by similar amounts.

The bright spot came in secondary outcomes. The researchers found that attention improved more in the exercise arm at 6 and 12 months, and memory improved at 6 months, though the memory advantage faded by the end of the year. These findings could be statistical false positives. Researchers also suspect the health and wellness group was no true control: coaching contact and a modest drop in body mass index, may have helped those women too.

The second paper (DOI: 10.1093/jnci/djag296) looked at a smaller subset of patients—55 health and wellness group participants and 69 exercise group participants—and compared their blood samples looking for DNA methylation, the basis of “epigenetic clocks.” At the start, women in both study arms looked biologically older than their birth certificates, with the exercise group being the oldest, by roughly 8.7 years on one clock model. But over the year, the exercise group aged more slowly on two clock models, GrimAge2 and DNAmFitAge. The comparison group’s clocks ran at nearly twice normal speed in the first six months, while the exercise group’s were essentially halted. Six other clock models plus a telomere length estimate showed no difference. The team also found methylation differences in genes tied to BDNF, a protein involved in brain plasticity, and proposed that as a pathway linking exercise to brain health. The second paper reports that faster epigenetic aging tracked with worse attention and self-reported cognition in the health and wellness group.

One Trial, Many Conclusions

The two papers are not independent confirmations of each other, but instead they suggest a hypothesis that exercise slows aging biology and that this may protect attention, but the hypothesis still needs to be tested in bigger, better-controlled studies.

“Attention is central to our everyday activities. It helps us follow conversations, absorb information and complete tasks without making errors, so the sustained improvements we saw in this trial is particularly encouraging,” said Sheri Hartman, PhD, lead author of the study, professor at UC San Diego Herbert Wertheim School of Public Health and Human Longevity Science and a member of Moores Cancer Center in a press release. “It is also encouraging that participants achieved this benefit with a modest, attainable increase in physical activity.”

Paula Desplats, professor of neurology at The Ohio State University, adjunct professor of neuroscience at UC San Diego School of Medicine and co-senior author of the companion study, added: “What is particularly striking about these findings is that the effects of exercise were measurable both at the molecular level and in cognitive performance,” she said in the same press release. “The changes we saw in markers of epigenetic aging suggest that even a relatively modest increase in physical activity may influence biological processes that help keep the brain healthy. This gives us an important clue about how exercise may help protect brain function after cancer treatment.”