Genetic regulation of gene expression and splicing during a 10-year period of human aging
| Autor: | David A. Knowles, Siddhartha Jaiswal, Mauro Pala, Lars Lind, Kevin S. Smith, Nathan S. Abell, Matthew G. Durrant, David Schlessinger, Chiara Sabatti, Erik Ingelsson, Michael J. Gloudemans, Brunilda Balliu, Olivia M. De Goede, Boxiang Liu, Naomi L. Cook, Francesco Cucca, Xin Li, Stephen B. Montgomery |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Aging lcsh:QH426-470 Population Longevity Biology Transcriptome 03 medical and health sciences 0302 clinical medicine Gene expression Genetics Humans Genetik education Gene lcsh:QH301-705.5 Aged 030304 developmental biology Medicinsk genetik Aged 80 and over Regulation of gene expression 0303 health sciences education.field_of_study Research Alternative splicing Human genetics Gene regulation lcsh:Genetics Gene Expression Regulation lcsh:Biology (General) RNA splicing Female Medical Genetics 030217 neurology & neurosurgery |
| Zdroj: | Genome Biology, Vol 20, Iss 1, Pp 1-16 (2019) Genome Biology |
| DOI: | 10.1186/s13059-019-1840-y |
| Popis: | Background Molecular and cellular changes are intrinsic to aging and age-related diseases. Prior cross-sectional studies have investigated the combined effects of age and genetics on gene expression and alternative splicing; however, there has been no long-term, longitudinal characterization of these molecular changes, especially in older age. Results We perform RNA sequencing in whole blood from the same individuals at ages 70 and 80 to quantify how gene expression, alternative splicing, and their genetic regulation are altered during this 10-year period of advanced aging at a population and individual level. We observe that individuals are more similar to their own expression profiles later in life than profiles of other individuals their own age. We identify 1291 and 294 genes differentially expressed and alternatively spliced with age, as well as 529 genes with outlying individual trajectories. Further, we observe a strong correlation of genetic effects on expression and splicing between the two ages, with a small subset of tested genes showing a reduction in genetic associations with expression and splicing in older age. Conclusions These findings demonstrate that, although the transcriptome and its genetic regulation is mostly stable late in life, a small subset of genes is dynamic and is characterized by a reduction in genetic regulation, most likely due to increasing environmental variance with age. |
| Databáze: | OpenAIRE |
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