Aging Muscle Weakens Cancer Defenses, but Exercise Fights Back

As muscles age and weaken, they may inadvertently create conditions that allow tumors to grow, but exercise could help reverse that process. That is the central finding of a new study by Duke-NUS scientists, published in Nature Communications, which establishes a direct biological link between aged muscle and cancer progression.

The research focuses on extracellular vesicles, tiny particles that cells use to communicate with one another. The team found that aging muscle releases fewer of these vesicles, and that their composition changes with age in ways that reduce their ability to suppress tumor development. Specifically, aged muscle contains lower levels of miR-7a-5p, a microRNA that plays a role in restraining tumor growth by regulating gene expression.

The effects of aging muscle are particularly visible in sarcopenia, a condition marked by the progressive loss of skeletal muscle mass and strength. In Singapore, sarcopenia affects nearly one in three seniors aged 60 and above, with consequences for mobility, independence, and quality of life. Working with collaborators from Singapore General Hospital and Cardiff University, the research team found that sarcopenic muscle secretes fewer extracellular vesicles, further diminishing these protective signals.

Importantly, the study also found that the pathway controlling the release of extracellular vesicles from muscle declines with age but can be reactivated through exercise, pointing to a practical intervention for preserving this protective function.

Senior author Tang Hong-Wen explained: "Muscle cells use extracellular vesicles to send messages and influence how other cells behave, but exactly how these messages are delivered and received is not fully understood. Our research uncovers this hidden process, showing that as muscles weaken with age, these signals can change in ways that can promote tumor growth."

Co-author Kenon Chua added that "Clinically, we observe an association between advanced cancer and low muscle mass. This is a novel study which illustrates how healthy muscle can potentially inhibit tumor growth... With advanced age, it is even more important to engage in regular resistance and aerobic exercises in order to maintain healthy muscle volume."

The researchers plan to validate their findings in human samples and explore whether extracellular vesicles, and the miR-7a-5p they carry, could serve as biomarkers for assessing cancer risk in people with sarcopenia.