Genetic regulation of gene expression and splicing during a 10-year period of human aging.
Genome Biol
; 20(1): 230, 2019 11 04.
Article
in En
| MEDLINE
| ID: mdl-31684996
ABSTRACT
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.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Aging
/
Gene Expression Regulation
/
Alternative Splicing
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Aged
/
Aged80
/
Female
/
Humans
/
Male
Language:
En
Journal:
Genome Biol
Journal subject:
BIOLOGIA MOLECULAR
/
GENETICA
Year:
2019
Type:
Article
Affiliation country:
United States