Glycocalyx-targeted therapy prevents age-related muscle loss and declines in maximal exercise capacity.

Age-related declines in cardiovascular function contribute to reduced physical capacity, both of which are independent predictors of mortality. We have previously demonstrated that glycocalyx-targeted therapy with Endocalyx™ that contains high-molecular-weight hyaluronan (HMW-HA) improves cardiovascular health in old age, raising the possibility that HMW-HA also plays a role in age-related physical dysfunction. Here, we first demonstrate that tamoxifen-inducible deletion of Has2, which produces HMW-HA, leads to glycocalyx depletion, decreases exercise capacity, and impairs skeletal muscle respiratory capacity. We then sought to determine the effects of Endocalyx™ on physical function in old mice. Young (7 months) and old (29 months) mice underwent standard diet or Endocalyx™-supplemented diet for 10 weeks. Glycocalyx thickness was higher in young and Endocalyx™-treated old mice compared to standard diet-fed old mice. While standard diet-fed old mice demonstrated a reduction in running exercise capacity over the intervention, Endocalyx™-supplemented diet prevented this age-related decline. Gastrocnemius citrate synthase activity, a marker of mitochondrial content in skeletal muscle, was lower in standard diet-fed old mice compared to young and Endocalyx™-treated old mice. Collectively, these findings suggest that glycocalyx integrity is a critical determinant of physical function and that glycocalyx-targeted interventions may be a viable therapeutic strategy to treat age-related physical dysfunction.