Transcriptional analysis of PBMCs reveals sex specific changes in the aging of the immune system
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE65219 | GEO | 2015/01/22
REPOSITORIES: GEO
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2013-01-10 | E-GEOD-40366 | biostudies-arrayexpress
Project description:Aging and sex have a strong influence on the functional capacity of the immune system. In general, the immune response in females is stronger than that in males, but there is little information about the effect of aging on this difference. To address this question, we performed a transcriptomic analysis of peripheral blood mononuclear cells derived from nonagenarians and young controls. We found 337 and 269 genes to be differentially expressed (p<0.05, fold change >1.5 or <-1.5) in nonagenarian females and males, respectively; 177 of these were changed in both sexes. An analysis of the affected signaling pathways revealed a clear sex bias: the number of significantly changed pathways was 43 in females and 40 in males; 23 were shared. These data show that the effects of aging on the immune system are significantly different in males and females. Our study population consisted of 146 nonagenarians (103 females, 43 males) and 30 young controls (19-30 years of age, 21 females, 9 males). In our study, we analyzed the gene expression difference between nonagenarian and control women as well as between nonagenarian and control males and then compared these results.
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Project description:Long-term memory formation is dependent on gene expression changes in the hippocampal region of the brain. Aging-related memory impairments and incidence of pathological memory disorders such as Alzheimer’s disease differ between males and females, and yet little is known about how aging-related changes to the transcriptome and chromatin environment differs between sexes in the hippocampus. To investigate this question, we compared the chromatin accessibility landscape and gene expression/alternative splicing pattern of young adult and aged mouse hippocampus of both males and females using ATAC-seq and RNA-seq. We detected significant aging-dependent changes in the expression of genes involved in immune response, cell adhesion, and synaptic function, and aging-dependent changes in the alternative splicing of myelin sheath genes. We found significant sex-bias in the expression and alternative splicing of hundreds of genes, including aging-dependent female-biased expression of myelin sheath genes and aging-dependent male-biased expression of genes involved in synaptic activity. Aging was associated with increased chromatin accessibility in both male and female hippocampus, especially in repetitive elements, and with an increase in LINE1 transcription. We detected significant sex-bias in chromatin accessibility in both autosomes and the X chromosome, with male-biased accessibility enriched at promoters and CpG-rich regions. Overall, sex differences in both gene expression and chromatin accessibility were amplified with aging, revealing that although some aspects of hippocampal aging are sex-independent, underlying sex differences in gene expression and chromatin dynamics in aging may shed light on sex differences in aging-related and pathological memory loss.
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