Aging is characterized by a decline in skeletal muscle mass and strength, coupled with accumulation of fat tissue, impairing mobility and quality of life in 45% of individuals over 65 years of age. While muscle stem cells (MuSCs) have a remarkable capacity to maintain and repair skeletal muscle throughout adulthood, they decline in regenerative capacity during aging. The goal of this proposal is to elucidate dysregulated functions of MuSCs in human aged tissues and identify pharmacological targets to enhance the function of dysfunctional subsets or amplify the residual functional subsets. During the first 12 months of this grant period we have made significant advances toward the aims that will allow us to address the remaining aspects of the goals of the grant.
We have, for the first time, achieved:
Identification of novel subsets within the human muscle stem/progenitor cell population using multidimensional single-cell mass cytometry (CyTOF);
Prospective isolation of a fully functional human muscle stem cell population;
Demonstration that human muscle stem cells regenerate injured muscle fibers following transplantation into NSG mice;
Verification that engrafted human muscle stem cells home to the stem cell niche and respond to muscle injury, thereby constituting a stem cell reservoir to meet future needs for regeneration;
Observed that the number of human muscle stem cells decrease in aged muscle tissue.