Year: 2025
Type: book-chapter
Abstract: The concept that unrepaired DNA damages are the underlying cause of aging has been supported by substantial evidence since it was first proposed in 1967. Aging is a broadly general characteristic of eukaryotes, including single-celled organisms such as paramecia. However, aging has mainly been studied in mammals. The two major causes of aging appear to be unrepaired DNA damage and epigenetic methylations or demethylations of cytosines that remain after the repair of DNA damage. Numerous studies have described increases in DNA damage with age in a variety of mammalian cell types (e.g., brain, muscle, liver, kidney, oocytes, and stem cells). In humans, several inherited genetic disorders caused by deficient repair of DNA damages are associated with premature aging. Expression of the approximately 20,000 genes in the human genome is controlled by genomic sequences referred to as enhancers and promoters. Enhancers and promoters are subject to epigenetic modifications. In promoter DNA, epigenetic alterations include methylations or demethylations of cytosines within CpG islands. With respect to enhancer DNA, epigenetic methylations or demethylations of transcription factor binding sites can alter enhancer activity. DNA repair activity often leaves behind epigenetic alterations that repress or amplify the activities of enhancer and promoter sequences. Epigenetic modifications due to DNA repair accumulate with age, thus contributing to the deficits seen as aging. Thus, aging at the cellular level is apparently due to both the accumulation of unrepaired DNA damages and the processes that repair DNA but result in lasting detrimental epigenetic alterations of gene expression.
Source: Genetics.
Parent work: Gene Expression - From Code to Cure
Authors: Carol Bernstein, Harris Bernstein
Institution: University of Arizona
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W4416227032