Abstract
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.
Highlights
Aging is a multifactorial process during which molecular alterations such as genetic and epigenetic mutations accumulate, resulting in decrepitude, frailty, and untimely death
On examination of the comparative transcriptome analyses of tissue samples of different ages and genotypes, we discovered that the expression levels of epidriver genes were altered with age and this ageassociated alteration of gene expression (A3GE) occurred progressively and, in particular, with the T cells displaying an interesting pattern of transcriptional drift
Using SiNG-PCRseq, we determined the amount of target transcript levels in the www.aging‐us.com skeletal muscle, brain, and splenic CD4+ T cells collected from wild type young and old mice and age-matched Huntington’s disease (HD) mice
Summary
Aging is a multifactorial process during which molecular alterations such as genetic and epigenetic mutations accumulate, resulting in decrepitude, frailty, and untimely death. Great strides have recently been made by studies that have led to a systematic categorization of the molecular hallmarks of aging [5]. These individual traits interact with the transcriptional network, which directly influences the transcriptomic profile. Transcriptomic signatures of aging have been reported for a number of species and tissues (for review, see [6]) These massive scale studies have mostly aimed at detecting either tissue specific or tissue independent aging marker genes that show statistically significant age related changes in expression levels, but a few have been interested in www.aging‐us.com identifying the patterns of transcriptional drift of individual genes and the elements that decide the pattern
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