Researchers here focus on a signaling mechanism that is diminished with age, the interaction between circulating prostaglandin E2 (PGE2) and its receptor EP4 on muscle stem cells. Levels of both PGE2 and its receptor decline with age, and this appears to broadly impair muscle stem cell function. The proof of that point is that delivering more PGE2 to aged mice improves muscle stem cell function, leading to an improved response following muscle injury.
Researchers examined the effects of circulating prostaglandin E2 (PGE2) and its receptor EP4 on muscle tissue. Their prior research had established that PGE2 signals during muscle injury trigger muscle stem cells to regenerate the muscles of young mice. In aged mice, the team found that EP4 expression on aged muscle stem cells are either lacking or reduced by half of those found in young stem cells. "PGE2 levels in muscle also decline with age, so we see blunted signaling from reductions in both the messenger and receiver. 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."
It is possible, however, to overcome the effects of aging and reset the intensity of this cellular signal. Researchers gave a stable form of PGE2 to aged mice after muscle injury and in conjunction with exercise. The treated mice gained more muscle mass and were stronger compared to untreated ones. The study revealed that PGE2 treatment restores stem cell function by modulating the activity of key transcription factors which reversed many of the age-related changes that the researchers observed. "The evidence suggests that PGE2 is not just acting on one mechanism. We've previously shown that PGE2 can also benefit the muscle fiber, and neurons that innervate the muscle. PGE2 has been implicated in the regenerative process and signaling for the intestine, liver, and several other tissues, potentially opening up an approach that could restore the renewing capacity of other aged tissues."
Link: https://sbpdiscovery.org/press/turning-back-time-on-muscle-stem-cells-to-prevent-frailty-from-aging/
View the full article at FightAging
