The world’s population is aging fast and with age comes a silent epidemic: sarcopenia, the gradual loss of muscle mass and function. This degenerative process increases frailty, reduces mobility, and raises the risk of hospitalization after injury or surgery. While exercise and nutritional interventions are widely promoted, their ability to reverse stem cell dysfunction has remained limited.
Reporting in Cell Stem Cell, researchers from Sanford Burnham Prebys, in collaboration with Stanford University, now reveal that a single dose of Prostaglandin E2 (PGE2), a naturally occurring lipid, can restore aged muscle stem cells, leading to improved regeneration and muscle strength in older mice.
“We knew that a major contributor is the muscle stem cells that are needed to repair muscle damage. They become dysfunctional with age. We’ve been trying to understand how aged stem cells are different from young and how to reverse these changes,” said Yu Xin (Will) Wang, PhD, assistant professor at Sanford Burnham Prebys.
Prostaglandin E2: a cellular wake-up call
The team’s previous work established that PGE2 is part of the body’s natural injury response system, activating muscle stem cells in young mice. But in aging tissue, both the levels of PGE2 and the expression of its receptor EP4 decline. “PGE2 is an alarm clock to wake up the stem cells and repair the damage. Aging essentially reduces the volume of the alarm and the stem cells have also put on ear plugs,” Wang explained.
By administering a stable form of PGE2 to aged mice after muscle injury and during exercise, the team observed restored stem cell function and muscle strength. Remarkably, the benefits were long-lasting, despite the short treatment duration. “What amazes me most is that a single dose of treatment is sufficient to restore muscle stem cell function, and that the benefit lasts far beyond the duration of the drug,” said Wang.
At the molecular level, the treatment reversed many age-associated transcriptional changes in the stem cells. “The genes that are upregulated during the aging process are downregulated after treatment, and vice versa,” Wang noted. This reprogramming hints at the plasticity of aging tissues, an encouraging sign for future regenerative therapies.
Beyond muscle: a broad regeneration strategy?
Unlike many emerging longevity interventions that target specific cellular pathways (e.g. senolytics or NAD+ boosters), PGE2 appears to have multifaceted effects. “The evidence suggests that PGE2 is not just acting on one mechanism,” Wang said. “We’ve previously shown that PGE2 can also benefit the muscle fiber, and neurons that innervate the muscle.”
PGE2 has also been linked to tissue regeneration in the intestine, liver, and other organs, raising the possibility of a more universal rejuvenation therapy. As Wang puts it, “The ultimate goal is to improve people’s quality of life by reversing the effects of aging.”
While this is still early-stage research in animal models, the findings suggest that even tissues impaired by age may still be coaxed back to youth-like function with the right molecular cues. Further studies will be needed to assess the safety, dosing, and duration of effect in humans—but the promise is clear: a future where the frailty of aging can be not just slowed, but reversed.
