DNA damage-induced stalling of transcription drives aging through gene expression imbalance

被引:2
|
作者
Sims, Austin A. [1 ]
Gurkar, Aditi U. [1 ,2 ]
机构
[1] Univ Pittsburgh, Aging Inst UPMC, Sch Med, 100 Technol Dr, Pittsburgh, PA 15219 USA
[2] Univ Pittsburgh, Aging Inst, Dept Med, 563 Bridgeside Point I,100 Technol Dr, Pittsburgh, PA 15241 USA
基金
美国安德鲁·梅隆基金会;
关键词
DNA damage; Aging; Transcription loss; Gene expression; NUCLEOTIDE EXCISION-REPAIR; PYRIMIDINE DIMERS; OXIDATIVE DAMAGE; COUPLED REPAIR; RNA; AGE; REVEALS; STRAND; CELLS; PHOSPHORYLATION;
D O I
10.1016/j.dnarep.2023.103483
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Age-related changes in gene expression have long been examined to understand the biology of aging. The hallmarks of aging are biological processes known to be associated with aging, but whether there is a unifying driver of these attributes, is not well understood. With the advent of technology over the last few years, it is quite clear that aging leads to global decline in transcription. In this Perspective, we highlight a new study in Nature Genetics that aimed to determine why global transcription rate reduces with age and how this phenomenon is the driver that interconnects multiple hallmarks of aging. This study recognizes that age-related accumulation of DNA damage, particularly transcription-blocking lesions, stalls RNA polymerase. This phenomenon affects longer genes leading to a gradual loss of transcription and skewing the transcriptome. In order to design a successful aging intervention, future work will be needed to test how some promising therapies in pre-clinical trials target affect transcriptional rate.
引用
收藏
页数:5
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