Scientists discover how to rejuvenate muscle stem cells and reduce fragility

As the population of developed countries ages, a new health problem emerges: frailty. This gradual muscle loss is accelerated by our cells' poor ability to repair damage and injuries, especially after a fall or surgery.

A reduction in muscle mass in older adults, known as sarcopenia, leads to increased frailty and movement problems. People with sarcopenia are more likely to be hospitalized and develop other comorbidities, primarily due to falls and fractures, which tend to lead to health deterioration.

In the search for a solution that can reverse or at least alleviate this scenario, a group of researchers from Stanford University (USA) analyzed a group of key cells in muscle repair: muscle stem cells.

These cells become dysfunctional with age, explains Yu Xin Wang, author of the study.

The results of their work, published in the journal Cell Stem Cell , demonstrate that it is possible to "rejuvenate" cells. According to their work, treating aged mice with a natural lipid, prostaglandin E2 (PGE2), improved muscle regeneration and strength.

In their experiments on aged mice, they found that EP4 expression in aged muscle stem cells was either absent or reduced by half compared to that found in young stem cells.

“PGE2 levels in muscle also decline with age, so we observed blunted signaling due to a reduction in both the messenger and the receptor,” Wang explains. “ PGE2 is like an alarm that activates stem cells and repairs the damage. Aging essentially lowers the volume of the alarm, and the stem cells have also gotten earplugs.”

However, it's possible to overcome the effects of aging and restore the intensity of this cellular siren. Wang and his team administered a stable form of PGE2 to elderly mice after muscle injury and in combination with exercise.

The treated mice gained more muscle mass and were stronger than the untreated mice.

"What surprises me most is that a single dose of treatment is enough to restore muscle stem cell function, and that the benefit lasts well beyond the duration of the drug," Wang says.

In addition to generating new muscle, stem cells remain in the tissue, where they maintain the effect of PGE2 and give the muscle greater regenerative capacity.

The study revealed that PGE2 treatment restored stem cell function by modulating the activity of key transcription factors , which reversed many of the age-related changes the researchers observed.

In addition to continuing to discover how to regenerate muscle and prevent sarcopenia and its associated health risks, Wang and his colleagues plan to expand their reach beyond muscle.