The neurological benefits of exercise are transferred through circulating blood factors, according to a new study, which shows that aged, sedentary mice that received plasma transfusions from regularly exercising mice gained the regenerative effects on the brain without having to hit the running wheel themselves. The results may help identify new therapeutic approaches to healthy brain aging. Research has shown that exercise conveys a wide variety of health benefits in both animal models and humans, including effects on the regenerative and cognitive function of aging brains. As such, exercise is considered helpful in promoting healthy aging and mitigating age-related neurodegenerative diseases. However, for some elderly individuals, physical frailty or poor health prevents their ability to exercise, highlighting a need for accessible approaches that confer similar therapeutic benefits as exercise. Alana Horowitz and colleagues evaluated whether exercise-induced circulating blood factors could transfer the restorative effects of exercise from one mouse to another. Horowitz et al. transferred plasma from regularly exercising adult (6-7 months) and aged (18 months) mice to largely inactive aged mice. Regardless of age, plasma from exercised mice resulted in improved function in the aged hippocampus of sedentary mice. Horowitz et al. identified GPLD1, a protein abundant in the liver and induced in the plasma of exercised mice, as a potential blood factor responsible for mediating the effect. What's more, the authors show that GPLD1 is also increased in the plasma of physically active elderly humans. "The ability to transfer the functional benefits of exercise though plasma adds to the current interest in plasma rejuvenation as an intervention to delay or reverse aspects of the aging process. However, the safety and ethical concerns inherent in provision and access to plasma remain to be addressed," write Victor Ansere and Willard Freeman in a related Perspective.