Human Lung Tissue Transcriptome: Influence of Sex and Age

Abstract

BackgroundSex and age strongly influence the pathophysiology of human lungs, but scarce information is available about their effects on pulmonary gene expression.MethodsWe followed a discovery-validation strategy to identify sex- and age-related transcriptional differences in lung.ResultsWe identified transcriptional profiles significantly associated with sex (215 genes; FDR < 0.05) and age at surgery (217 genes) in non-involved lung tissue resected from 284 lung adenocarcinoma patients. When these profiles were tested in three independent series of non-tumor lung tissue from an additional 1,111 patients, we validated the association with sex and age for 25 and 22 genes, respectively. Among the 17 sex-biased genes mapping on chromosome X, 16 have been reported to escape X-chromosome inactivation in other tissues or cells, suggesting that this mechanism influences lung transcription too. Our 22 age-related genes partially overlap with genes modulated by age in other tissues, suggesting that the aging process has similar consequences on gene expression in different organs. Finally, seven genes whose expression was modulated by sex in non-tumor lung tissue, but no age-related gene, were also validated using publicly available data from 990 lung adenocarcinoma samples, suggesting that the physiological regulatory mechanisms are only partially active in neoplastic tissue.ConclusionsGene expression in non-tumor lung tissue is modulated by both sex and age. These findings represent a validated starting point for research on the molecular mechanisms underlying the observed differences in the course of lung diseases among men and women of different ages.

Characterization of Sex-Based Dna Methylation Signatures in the Airways During Early Life

“…2 ). We filtered these genes based on experimental evidence of escaping X inactivation status and known female-biased expression in 4 different datasets of human lungs (N = 1,395; GSE30219, GSE31210, GSE37745, and GSE41271) 16 . Fig.…”

“…At least 15% of X-linked genes completely escape inactivation and many others have variable X-methylation and inactivation status 10 – 15 . As a result, females have higher gene dosage (enhanced expression) of some X-linked genes, which may lead to important biological sex-related differences in different cell systems and across life-span 16 . For instance the excessive expression of X-linked immune genes in females is thought to modify their immune responses conferring overall decreased risk against infections but higher risk for autoimmune conditions 8 .…”

Simultaneous transcriptome and methylome profiles of single mouse oocytes provide novel insights on maturation and aging

“…In recent years, there have been growing interests in molecular changes during human aging and senescence. Multiple studies have demonstrated that transcriptome profiles in various tissues, including lung, kidney, brain and peripheral blood cells, are altered during aging [7][8][9][10]. The difference between biological age and chronological age has been revealed in human dermal fibroblasts [11].…”

The effects of age, cigarette smoking, sex and race on the qualitative characteristics of lung transcriptome

“…Studies have shown that sex-biased gene expression is widespread across genomes on both sex chromosomes and autosomes [25,26]. Several studies have also reported that cigarette smoking [27] and race [28] could alert the gene expression levels, and the gene expression levels change with age in many organ tissues, including lung tissues [29]. However, whether those confounding factors could affect the REO of gene pairs is still unclear.…”