image: Figure 1. Impact of Has2 deletion on glycocalyx integrity and exercise capacity. (A) Glycocalyx thickness in gastrocnemius muscle microcirculation prior to tamoxifen injections (Wk 0) and 3 weeks post-tamoxifen administration (Wk 3) with representative images demonstrating changes in perfused diameter (red line segment) pre- and post-leukocyte (white x’s) passage with arrows representing direction of flow; scale bar = 50 μm. (B) Running time to exhaustion during maximal treadmill test pre- and post-tamoxifen administration. (C) Work performed during maximal treadmill test pre- and post-tamoxifen administration. (D) Gastrocnemius muscle citrate synthase activity. Data are presented as mean ± SEM. *P < 0.05 vs. Has2+/+; †P < 0.05 vs. Pre. N = 4–13/group.
Credit: Copyright: © 2025 Machin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
“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.”
BUFFALO, NY — October 14, 2025 — A new research paper was published in Volume 17, Issue 9 of Aging-US on August 30, 2025, titled, “Glycocalyx-targeted therapy prevents age-related muscle loss and declines in maximal exercise capacity.”
In this study, led by Daniel R. Machin from the University of New Mexico School of Medicine and the University of Utah, researchers found that protecting a fragile layer lining blood vessels, known as the glycocalyx, can prevent muscle deterioration and help maintain physical performance during aging. They also discovered that a supplement containing high-molecular-weight hyaluronan (HMW-HA), a key component of the glycocalyx, enabled older mice to preserve muscle mass and exercise capacity. These findings suggest that targeting the glycocalyx may offer a new approach to reduce frailty and support mobility in older adults.
As this layer degrades with age, it contributes to cardiovascular and muscular decline by impairing blood flow and vascular health. The study examined how preserving the glycocalyx using a therapy called Endocalyx™ affects physical function in aging mice.
Researchers first studied genetically modified mice lacking Has2, the enzyme responsible for producing HMW-HA. These mice had a thinner glycocalyx, reduced exercise performance, and lower mitochondrial function in their muscles, even though muscle size remained normal. This indicated that glycocalyx damage alone can directly impair physical performance.
The team then gave older mice a diet containing Endocalyx™ for 10 weeks. Compared to untreated controls, these mice maintained muscle mass and performed better on treadmill tests. Notably, the treated mice did not show the typical age-related decline in muscle strength and endurance. While the supplement did not fully restore youthful performance, it significantly slowed physical deterioration, suggesting a protective benefit. In contrast, untreated older mice lost both body mass and muscle volume during the same period.
“Taken together, these findings provide direct evidence of a role for HMW-HA in the modulation of exercise capacity.”
This research builds on prior evidence that the glycocalyx is essential for healthy blood vessel function. Since muscle health depends on proper blood flow and oxygen delivery, restoring the glycocalyx may help maintain strength and mobility with age. While more research is needed to confirm these results in humans, the findings point to a potential therapeutic approach to promote healthier aging.
DOI: https://doi.org/10.18632/aging.206313
Corresponding author: Daniel R. Machin — dmachin@salud.unm.edu
Abstract video: https://www.youtube.com/watch?v=S7HjCeXT8fU
Keywords: glycocalyx, aging, hyaluronan
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Journal
Aging-US
Method of Research
News article
Subject of Research
Animals
Article Title
Glycocalyx-targeted therapy prevents age-related muscle loss and declines in maximal exercise capacity
Article Publication Date
30-Aug-2025
COI Statement
The authors have no conflicts of interest to disclose.