Cell survival pathway linked to regeneration in aged skeletal muscle

Skeletal muscle stem cells (MuSCs) play a vital role in the repair and regenerative functions of our muscles after injury. As those of us over forty may know firsthand, this function declines with age and contributes to impaired muscle regeneration in older individuals. Despite what you may see in internet ads, there are currently no stem cell injection treatments that can reverse this decline in muscle regeneration function. However, thanks to a new report from Duke University’s Department of Medicine (Hematology), scientists are a step closer to identifying treatments that target molecular pathways related to cell survival. They hope that age- or disease-related muscular degeneration can be slowed or even reversed by identifying and restoring function of these molecular pathways.

Top to bottom muscle stem cells in young, middle-aged, old and geriatric mice. Blue is nuclei, red is cytoplasm and green shows autophagy.

Top to bottom: muscle stem cells in young, middle-aged, old and geriatric mice. Blue is cell nucleus, red is cytoplasm and green shows autophagy. Image courtesy James White

In this recently published report, Duke researcher James White and colleagues identified a molecular pathway that regulates several natural phases of the MuSC cell cycle. This pathway, the AMPK/p27Kip1 pathway, regulates key processes including autophagy (cellular recycling to turn old proteins and other substances into energy and materials for new structures) and apoptosis (cell death). Aging cells tend to exhibit less autophagy and more apoptosis, which ultimately leads to reduced regenerative and repair capacity in older adults.

In the paper, published in the journal Stem Cell Reports, White and colleagues found that the balance between the processes of autophagy and apoptosis is crucial in determining whether an MuSC survives and can assist with muscle repair. They found that MuSCs in aging mice exhibit less autophagy and more apoptosis, and are more susceptible to cell death than the MuSCs of younger mice.

White and colleagues determined that aging MuSCs have dysfunctional signaling of the AMPK/p27Kip1 molecular pathway. When they activated the AMPK/p27Kip1 molecular pathway in old MuSC, they found increased cell proliferation. In addition, restoring AMPK/p27Kip1 signaling increased the survival rate of transplanted aging MuSCs. White and colleagues conclude that this pathway could be an important potential therapeutic target for improving muscle regeneration in older individuals.

Citation: James P. White, Andrew N. Billin, et al, The AMPK/p27Kip1 Axis Regulates Autophagy/Apoptosis Decisions in Aged Skeletal Muscle Stem Cells, Stem Cell Reports, 2018,
https://doi.org/10.1016/j.stemcr.2018.06.014.

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