Abstract
Changes in the mean and variance of gene expression with age have consequences for healthy aging and disease development. Age-dependent changes in phenotypic variance have been associated with a decline in regulatory functions leading to increase in disease risk. Here, we investigate age-related mean and variance changes in gene expression measured by RNA-seq of fat, skin, whole blood and derived lymphoblastoid cell lines (LCLs) expression from 855 adult female twins. We see evidence of up to 60% of age effects on transcription levels shared across tissues, and 47% of those on splicing. Using gene expression variance and discordance between genetically identical MZ twin pairs, we identify 137 genes with age-related changes in variance and 42 genes with age-related discordance between co-twins; implying the latter are driven by environmental effects. We identify four eQTLs whose effect on expression is age-dependent (FDR 5%). Combined, these results show a complicated mix of environmental and genetically driven changes in expression with age. Using the twin structure in our data, we show that additive genetic effects explain considerably more of the variance in gene expression than aging, but less that other environmental factors, potentially explaining why reliable expression-derived biomarkers for healthy-aging have proved elusive compared with those derived from methylation.
Highlights
Aging is a complex process, characterized by a progressive decline in an organism’s biological function and change in phenotypic characteristics, which leads to an increased chance of developing disease and the death of the organism [1]
We have explored a large multi-tissue expression dataset to investigate the influence of aging on genetic regulation
We have extensively explored the relationship between changes in phenotypic variance with age, an under-studied effect of aging reported in multiple studies and in which global changes in phenotypic variance increase with age [2]
Summary
Aging is a complex process, characterized by a progressive decline in an organism’s biological function and change in phenotypic characteristics, which leads to an increased chance of developing disease and the death of the organism [1]. Others have attempted to understand the aging process by identifying common denominators of aging in different organisms [2]. Many of these hallmarks, such as genome instability, epigenetic alterations, loss of proteostasis and telomere attrition, are accompanied by changes in gene expression. Accepted: November 29, 2017 VC The Author(s) 2017.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
