Dr. Aguilar’s work on Vitamin A’s impact on skeletal muscle aging offers insight into simple ways people may be able to make health improvements in longevity and quality of life.
U-M BME’s Carlos Aguilar, Associate Professor, Biomedical Engineering, and his lab team are exploring research that could revolutionize the ways that science understands the connections between aging and muscle health. In a world facing a demographic shift toward an older population, Dr. Aguilar’s work on Vitamin A’s impact on skeletal muscle aging offers insight into simple ways people may be able to make health improvements in longevity and quality of life.
For Dr. Aguilar, the research began with a statistic: “Over the last hundred years, from 1950 to 2050, we’re going to see an approximate tripling of the number of people over the age of 65,” he noted. “That tripling presents significant challenges for healthcare, particularly in addressing the reduction in mobility and the increase in frailty that elderly people experience.”
This phenomenon is in part attributed to sarcopenia—age-associated loss of muscle mass and function. An integral part of Dr. Aguilar’s research focuses on skeletal muscle stem cells, the tissue’s intrinsic repair system. “As we age, impairments in these stem cells result in
to persistent tissue damage, and likely irreversible, structural and functional deficits,” Dr. Aguilar explained. In this research, a common dietary element–Vitamin A–takes center stage.
One potential source of the deleterious behavior that occurs in old age is lower vitamin consumption. Specifically, an underexplored vitamin that contributes to vision, immunity and skin is retinoic acid-induced signaling from Vitamin A, but its potential in skeletal muscle and stem cell aging was not fully understood. Dr. Aguilar explained his team’s discovery. “We were fascinated with Vitamin A as “epidemiological studies have shown that regular diet supplemented with higher intake of antioxidant vitamins display improvements in health during aging. However, connecting functionality of adult stem cells with metabolite sensing pathways derived from vitamins in aging is underexplored,” he said.
Dr. Aguilar further describes: “We started by administering a Vitamin A-free diet to young mice and found after two months, muscle stem cells from mice fed Vitamin-A free diet resembled features found in much older mice. Specifically, Vitamin-A seemed to support the activity of mitochondria and how these stem cells use energy.” This startling revelation drove Dr. Aguilar and his team to explore molecular mechanisms of how Vitamin A made this impact in a short time. They focused on the cellular receptor for vitamin A, called STRA6, which was lost in old age and detected that delivering a small molecule cocktail to stimulate STRA6 and other vitamin A signaling targets resulted in better mitochondrial function and partial rejuvenation of old aged muscle stem cells.
The implications of Dr. Aguilar’s research suggest that modest dietary adjustments could result in positive change. “A balanced diet, rich in protein and vegetables, may help maintain muscle health,” Dr. Aguilar noted. Yet, he noted, “There’s no magic bullet; diet and exercise remain cornerstones of healthy aging.”
In the long-term, Dr. Aguilar said, “We’re developing targeted therapeutics to home in on muscle stem cells without affecting other cell types and tissues.” This targeted approach is crucial, considering skeletal muscle constitutes a significant portion of the human body.
As his lab explores these avenues, Dr. Aguilar appreciates the support and collaboration that fuels the research. Notably, he credited former student Paula Fraczek, a recent Ph.D. graduate whose work in this area helped bring discoveries to light, and acknowledges crucial funding from the National Science Foundation and the Hevolution Foundation.
In an era where the grocery store may offer as much promise as the pharmacy, Dr. Aguilar’s work blends modern science with advice that physicians have given for years—diets profoundly impact health. As populations age, insights into Vitamin A could serve as a helper to improve the aging process.
The complete journal article is available here: Vitamin A-Retinoic Acid Contributes to Muscle Stem Cell and Mitochondrial Function Loss in Old Age Paula M. Fraczek, … , Jacqueline A Larouche, Carlos A. Aguilar Published March 25, 2025
Citation Information: JCI Insight. 2025. https://doi.org/10.1172/jci.insight.183706. View: Text | PDF