Distinct patterns of gene expression in human cardiac fibroblasts exposed to rapamycin treatment or methionine restriction

Abstract

Both methionine restriction and rapamycin treatment are robust longevity-enhancing regimens for which the mechanisms remain unclear. Cellular senescence is a major contributor to the aging process, and we find that both the methionine and rapamycin regimens delay or prevent activation of the senescence program in human cells. Using a transcriptome-wide analysis, we examined the impact of methionine restriction and rapamycin treatment on senescence-associated gene expression in human cardiac fibroblasts. Our findings have been integrated into gene expression data sets from human lung and skin fibroblasts during senescence. The data demonstrate both common and tissue-specific aspects to the senescent phenotype in these cell types. For example, cardiac fibroblasts express brain naturetic peptide, a clinically relevant marker for cardiac failure, whereas senescent cells from all three tissues express at least one of the insulin-like growth factor (IGF)-binding proteins. The IGF-binding proteins are tissuespecificmediators of IGF-1, a growth factor required for proliferation of all tissues. These data suggest that senescent cells serve tissue-specific roles. Moreover, the prolongevity regimens produce distinct patterns of gene expression.