RNA sequencing comparing centenarian and middle-aged women lymphoblastoid cell lines identifies age-related dysregulated expression of genes encoding selenoproteins, heat shock proteins, CD99, and BID

Abstract

Women typically live longer than men, and constitute the majority of centenarians. We applied RNA-sequencing (RNA-seq) of blood-derived lymphoblastoid cell lines (LCLs) from women aged 60-80 years and centenarians (100-105 years), validated the RNA-seq findings by real-time PCR, and additionally measured the differentially expressed genes in LCLs from young women aged 20-35 years. Top RNA-seq genes with differential expression between the age groups included three selenoproteins (GPX1, SELENOW, SELENOH) and three heat shock proteins (HSPA6, HSPA1A, HSPA1B), with the highest expression in LCLs from young women, indicating that young women are better protected from oxidative stress. The expression of two additional genes, BID encoding BH3-interacting domain death agonist and CD99 encoding CD99 antigen, showed unique age dependence, with similar expression levels in young and centenarian women while exhibiting higher and lower expression levels, respectively, in LCLs from women aged 60-80 years compared with the two other age groups. This age-related differential expression of BID and CD99 suggests elevated inflammation susceptibility in middle-aged women compared with either young or centenarian women. Our findings, once validated with human peripheral blood mononuclear cells and further cell types, may lead to novel healthy aging diagnostics and therapeutics.