Muscle Stem Cell Rejuvenation Restores Strength

Much of the work on the aging of stem cells in recent years has focused on muscle stem cells, and has shown that to a large degree the progressive decline in function with age is not due to a loss of stem cells, but rather because these cells become less active and stop doing their jobs. This is probably an evolved reaction to rising levels of cellular damage that serves to reduce the risk of cancer, but which comes at the cost of increasing frailty as tissue maintenance falters.

Researchers are making inroads into understanding the signal mechanisms involved in this process of stem cell decline. Work is already underway on the development of potential treatments based on at least temporarily overriding these signals in the old. Here is another example of relevant research in this field, which uncovers an aspect of aging in stem cells that is inherent to the cells themselves rather than being a property of the surrounding tissue and its protein signals:

The elderly often suffer from progressive muscle weakness and regenerative failure. We demonstrate that muscle regeneration is impaired with aging owing in part to a cell-autonomous functional decline in skeletal muscle stem cells (MuSCs). Two-thirds of MuSCs from aged mice are intrinsically defective relative to MuSCs from young mice, with reduced capacity to repair myofibers and repopulate the stem cell reservoir in vivo following transplantation. This deficiency is correlated with a higher incidence of cells that express senescence markers and is due to elevated activity of the p38α and p38β mitogen-activated kinase pathway.

We show that these limitations cannot be overcome by transplantation into the microenvironment of young recipient muscles. In contrast, subjecting the MuSC population from aged mice to transient inhibition of p38α and p38β in conjunction with culture on soft hydrogel substrates rapidly expands the residual functional MuSC population from aged mice, rejuvenating its potential for regeneration and serial transplantation as well as strengthening of damaged muscles of aged mice. These findings reveal a synergy between biophysical and biochemical cues that provides a paradigm for a localized autologous muscle stem cell therapy for the elderly.