Pan-senescence transcriptome analysis identified RRAD as a marker and negative regulator of cellular senescence

Cellular senescence, an irreversible proliferative arrest, functions in tissue remodeling during development and is implicated in multiple aging-associated diseases. While senescent cells often manifest an array of senescence-associated phenotypes, such as cell cycle arrest, altered heterochromatin architecture, reprogrammed metabolism and senescence-associated secretory phenotype(SASP), the identification of senescence cells has been hindered by lack of specific and universal biomarkers. To systematically identify universal biomarkers of cellular senescence, we integrated multiple transcriptome data sets of senescent cells obtained through different in vitro manipulation modes as well as age-related gene expression data of human tissues. Our analysis showed that RRAD (Ras-related associated with diabetes) expression is up-regulated in all the manipulation modes and increases with age in human skin and adipose tissues. Microarray experiments were performed to determine the lncRNA expression in corresponding (normal human fibroblasts) NHFs. We used NHFs at passage 62 as replicative senescence model and NHFs at passage 11 as control. To obtain oxidative stress-induced senescent cells, we applied a single dose of 600μM H2O2 to NHFs at passage 11 for five days.