Alterations in the TGFβ signaling pathway in myogenic progenitors with age

Abstract

Myogenic progenitors in adult muscle are necessary for the repair, maintenance and hypertrophy of post-mitotic muscle fibers. With age, fat deposition and fibrosis contribute to the decline in the integrity and functional capacity of muscles. In a previous study we reported increased accumulation of lipid in myogenic progenitors obtained from aged mice, accompanied by an up-regulation of genes involved in adipogenic differentiation. The present study was designed to extend our understanding of how aging affects the fate and gene expression profile of myogenic progenitors. Affymetrix murine U74 Genechip analysis was performed using RNA extracted from myogenic progenitors isolated from adult (8-month-old) and aged (24-month-old) DBA/2JNIA mice. The cells from the aged animals exhibited major alterations in the expression level of many genes directly or indirectly involved with the TGFβ signaling pathway. Our data indicate that with age, myogenic progenitors acquire the paradoxical phenotype of being both TGFβ activated based on overexpression of TGFβ-inducible genes, but resistant to the differentiation-inhibiting effects of exogenous TGFβ. The overexpression of TGFregulated genes, such as connective tissue growth factor, may play a role in increasing fibrosis in aging muscle. © Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland 2004.