FOXO is Involved in the Preservation of Muscle Stem Cell Function with Age

Researchers here note that the FOXO signaling pathway appears to help maintain function in a subset of muscle stem cells all the way into later life. Muscle stem cell activity declines with age, even while the evidence suggests that the populations are largely intact and able to act if placed into a more youthful environment. This decline may be an evolved reaction to the molecular damage of aging that serves to reduce the cancer risk inherent in cell activity in a damaging environment, or it may be the consequence of damage and dysfunction in the stem cell niche in which muscle stem cells reside, or both. This loss of stem cell activity is an important contributing cause of sarcopenia, the age-related loss of muscle mass and strength that affects all individuals to an ever increasing degree over time. Thus the research community is interested in the discovery of ways to put aging muscle stem cells back to work.

Skeletal muscle regeneration depends on a muscle stem cell population (satellite cells) in a dormant or quiescent state, a situation that can be triggered by damage or stress to form new muscle fibres and expand in new stem cells. The regenerative functions of these stem cells are known to decline with ageing. Researchers have found in experiments with mice that all muscle stem cells, despite being quiescent, are not equal, and have identified a subgroup that maintains its regenerative capacity over time, declining only at geriatric age.

The researchers have shown that this subgroup of quiescent stem cells has a greater regenerative capacity through the activation of the FoxO signalling pathway (previously associated with longevity), which maintains the expression of a youthful gene programme throughout life; however, at geriatric age, FoxO activation in this subgroup of cells is lost, causing their loss of functionality.

According to the results, compounds that activate FoxO may have a rejuvenating effect on aged muscle stem cells, opening the way to improve the health of elderly people who are debilitated by the loss of muscle mass. It may also be useful for persons who have lost muscle mass as a result of neuromuscular diseases or effects associated with cancer or infectious or inflammatory diseases.

Link: https://www.eurekalert.org/pub_releases/2020-10/upf--ias102720.php