Hirotaka Iijima, PhD, PT, and Fabrisia Ambrosio, PhD, MPT, of the Discovery Center for Musculoskeletal Recovery within the Department of Physical Medicine and Rehabilitation at Mass General Brigham, are the lead and senior authors of a paper published in Nature Aging , “ Exercise enhances aged chondrocyte health through microRNA29–enriched extracellular vesicles .”
Q: What challenges or unmet needs make this study important?
Osteoarthritis is one of the leading causes of pain, disability and loss of mobility among older adults worldwide. While regular exercise is strongly recommended for people with osteoarthritis and is known to protect joint tissue, we still do not fully understand the biological mechanisms by which this protection occurs. Gaining a better understanding of how exercise elicits this benefit will help us develop new interventions and therapies that reproduce its effects, especially for patients who face barriers to participating in regular exercise.
Q: What central question(s) were you investigating?
We wanted to understand whether circulating extracellular vesicles (EVs)—nanoparticles released by cells into the bloodstream—play a role in mediating the protective effects of exercise on joint health. Specifically, we investigated whether exercise alters the molecular cargo carried by EVs and whether these changes can directly improve cartilage health in aging and osteoarthritic joints.
Q: What methods or approach did you use?
Our approach spanned EV analyses, cell culture experiments, mouse studies of aging-associated osteoarthritis and human exercise interventions.
In the human portion of our study, older adults participated in a structured aerobic exercise program, and we collected blood samples before and after three months of training. Using these blood samples, we analyzed how aerobic exercise altered the molecular contents of circulating EVs and evaluated the biological effects of these exercise-derived EVs on cartilage cells and joint tissues. We also identified and tested specific molecules that were enriched in EVs after training.
Q: What did you find?
We found that moderate-intensity exercise significantly changed the molecular cargo of circulating EVs in ways that promoted cartilage health and tissue resilience. Specifically, EVs collected after exercise improved cellular and cartilage tissue health in the knee joint.
Among the molecular signals enriched after exercise, we identified microRNA-29 as a key mediator of the beneficial effects. Delivery of microRNA-29 to aged osteoarthritic joints restored more youthful characteristics in cartilage cells and reduced features associated with joint degeneration.
Q: What are the real-world implications, particularly for patients?
Our findings provide new insight into how exercise promotes joint health and help explain why physical activity is beneficial for people with osteoarthritis. By identifying specific biological signals that are altered by exercise, this work brings us closer to understanding the molecular pathways underlying rehabilitation interventions.
Looking forward, these discoveries may inform the development of new treatment approaches for osteoarthritis, including therapies that utilize EVs or their molecular cargo. These strategies would be especially impactful for people who are unable to engage in sufficient physical activity because of pain, disability or other health limitations, and show how regenerative medicine can be paired with traditional rehabilitation principles and approaches.
We anticipate that this work will help guide the design of clinical programs that are focused on maximizing the biological responses associated with joint protection and tissue health.
Q: What part of this work feels most meaningful to you personally?
As physical therapists, we are motivated by a simple but important question: Why and how does exercise work? While there is much left to learn about why it’s one of the most effective treatments out there for a variety of musculoskeletal conditions, this study represents an important step forward in our collective knowledge. The possibility that these findings may eventually help patients, especially those unable to exercise sufficiently, is meaningful to us—reinforcing why we chose this field.
Authorship: In addition to Iijima and Ambrosio, Mass General Brigham authors include Kandarp M. Dave, Kai Wang and Adam Khay. Additional authors include Ella D'Amico, Wan-Yee Tang, Renee J. Rogers and John M. Jakicic.
Paper cited: Iijima H., et al . “Exercise enhances aged chondrocyte health through microRNA29–enriched extracellular vesicles.” Nature Aging . DOI: 10.1038/s43587-026-01225-9
Funding : This study was supported by grants from the National Institute on Aging (NIA) (R01AG052978, R01AG061005, R01AG087565, R01AG092299 and R01AG090356).
Disclosures: The authors declare no competing interests.
Nature Aging
Experimental study
Animals
Exercise enhances aged chondrocyte health through microRNA-29-enriched extracellular vesicles
29-Sep-2026
The authors declare no competing interests.