Research Paper Volume 10, Issue 4 pp 789—807
Age-associated bimodal transcriptional drift reduces intergenic disparities in transcription
- 1 Development and Differentiation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, South Korea
- 2 Department of Molecular and Life Sciences, Hanyang University, Sangnok-gu, Ansan, Gyeonggi-do 15588, South Korea
- 3 Mibyeong Research Center, Korea Institute of Oriental Medicine (KIOM), Daejeon 305-811, Korea
received: March 4, 2018 ; accepted: April 20, 2018 ; published: April 27, 2018 ;https://doi.org/10.18632/aging.101428
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Copyright: Min et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
This study addressed the question of how well the quantitative transcriptome structure established in early life is maintained and how consistently it appears with increasing age, and if there is age-associated alteration of gene expression (A3GE), how much influence the Huntington’s disease (HD) genotype exerts on it. We examined 285 exonic sequences of 175 genes using targeted PCR sequencing in skeletal muscle, brain, and splenic CD4+ T cells of wild-type and HD mice. In contrast to the muscle and brain, T cells exhibited large A3GE, suggesting a strong contribution to functional decline of the organism. This A3GE was markedly intensified in age-matched HD T cells, which exhibited accelerated aging as determined by reduced telomere length. Regression analysis suggested that gene expression levels change at a rate of approximately 3% per month with age. We found a bimodal relationship in A3GE in T cells in that weakly expressed genes in young mice were increasingly transcribed in older animals whereas highly expressed genes in the young were decreasingly expressed with age. This bimodal transcriptional drift in the T cell transcriptome data causes the differences in transcription rate between genes to progressively reduce with age.
A3GE: age-associated alteration of gene expression; HD: Huntington’s disease; WT: Wild type; SiNG-PCRseq: spiking-in a neighbor genome for competitive PCR-amplicon sequencing; wRMSD: weighted root mean square deviation; wo: wild-type old; wy: wild-type young; ho: Huntington old; hy: Huntington young; HEGs: highly expressed genes; LEGs: lowly expressed genes; PRG: PRC-regulated gene.