Senescence of muscle progenitor cells: impact on human myogenesis and muscle aging

National Institute On Aging

Investigators

Abstract

Compared with bulk gene expression, single-cell analysis of senescent fibroblasts has revealed a great deal of heterogeneity in the patterns of expressed RNAs, including those RNAs that govern the trait SASP (senescence-associated secretory phenotype). Therefore, understanding the heterogeneity of single senescent cells may provide the new insight to identify specific genetic networks of senescence-associated genes and key target genes for extended therapeutic discovery. Moreover, senescence-associated receptors have the potential to target and restore the senescence-associated functional decline that results from impaired muscle regeneration and muscle aging. However, the functional heterogeneity of senescent muscle cells is unknown. In this proposal, we will systematically examine the phenotype and bulk transcriptome of senescent human primary myoblasts (Aim 1), and identify the muscle-specific senescence-associated genes by comparing with other senescence programs (Aim 2). We will further investigate the potential of targeting senescent myoblast membrane proteins and intervening in muscle aging (Aim 3).