TY - JOUR
T1 - Epigenetics, DNA damage, and aging
AU - Soto-Palma, Carolina
AU - Niedernhofer, Laura J.
AU - Faulk, Christopher D.
AU - Dong, Xiao
N1 - Publisher Copyright:
© 2022 Soto-Palma et al.
PY - 2022/8/15
Y1 - 2022/8/15
N2 - Over the course of a human lifespan, genome integrity erodes, leading to an increased abundance of several types of chromatin changes. The abundance of DNA lesions (chemical perturbations to nucleotides) increases with age, as does the number of genomic mutations and transcriptional disruptions caused by replication or transcription of those lesions, respectively. At the epigenetic level, precise DNA methylation patterns degrade, likely causing increasingly stochastic variations in gene expression. Similarly, the tight regulation of histone modifications begins to unravel. The genomic instability caused by these mechanisms allows transposon element reactivation and remobilization, further mutations, gene dysregulation, and cytoplasmic chromatin fragments. This cumulative genomic instability promotes cell signaling events that drive cell fate decisions and extracellular communications known to disrupt tissue homeostasis and regeneration. In this Review, we focus on age-related epigenetic changes and their interactions with age-related genomic changes that instigate these events.
AB - Over the course of a human lifespan, genome integrity erodes, leading to an increased abundance of several types of chromatin changes. The abundance of DNA lesions (chemical perturbations to nucleotides) increases with age, as does the number of genomic mutations and transcriptional disruptions caused by replication or transcription of those lesions, respectively. At the epigenetic level, precise DNA methylation patterns degrade, likely causing increasingly stochastic variations in gene expression. Similarly, the tight regulation of histone modifications begins to unravel. The genomic instability caused by these mechanisms allows transposon element reactivation and remobilization, further mutations, gene dysregulation, and cytoplasmic chromatin fragments. This cumulative genomic instability promotes cell signaling events that drive cell fate decisions and extracellular communications known to disrupt tissue homeostasis and regeneration. In this Review, we focus on age-related epigenetic changes and their interactions with age-related genomic changes that instigate these events.
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U2 - 10.1172/JCI158446
DO - 10.1172/JCI158446
M3 - Article
C2 - 35968782
AN - SCOPUS:85136833745
SN - 0021-9738
VL - 132
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 16
M1 - e158446
ER -