With the continued extension of lifespan, aging and age-related diseases have become a major medical challenge to our society. Aging is accompanied by changes in multiple systems. Among these, the aging process in the central nervous system is critically important but very poorly understood. Neurons, as post-mitotic cells, are devoid of replicative associated aging processes, such as senescence and telomere shortening. However, because of the inability to self-replenish, neurons have to withstand challenge from numerous stressors over their lifetime. Many of these stressors can lead to damage of the neurons' DNA. When the accumulation of DNA damage exceeds a neuron's capacity for repair, or when there are deficiencies in DNA repair machinery, genome instability can manifest. The increased mutation load associated with genome instability can lead to neuronal dysfunction and ultimately to neuron degeneration. In this review, we first briefly introduce the sources and types of DNA damage and the relevant repair pathways in the nervous system (summarized in Fig. 1). We then discuss the chromatin regulation of these processes and summarize our understanding of the contribution of genomic instability to neurodegenerative diseases.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560486 | PMC |
http://dx.doi.org/10.1016/j.jmb.2014.08.001 | DOI Listing |
J Occup Health
January 2025
Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Objectives: Natural fibrous mineral, asbestos, has been useful in industry for many centuries. In the 1960's, epidemiology had recognized the association between asbestos exposure and mesothelioma and the IARC designated all kinds of asbestos as Group 1 in 1987. However, various scientific enigmas remained regarding the molecular mechanisms of asbestos-induced mesothelial carcinogenesis.
View Article and Find Full Text PDFEnviron Sci Pollut Res Int
January 2025
Department of Biology, Hamilton College, Clinton, NY, USA.
Perfluorooctane sulfonic acid (PFOS) is an anthropogenic chemical found in aqueous film-forming foams (AFFFs) and many consumer products. Despite its environmental ubiquity and persistence, little is known about the effects of PFOS on stress levels in wild animals. Here, we examined PFOS bioaccumulation and correlations between PFOS exposure and oxidative stress in snapping turtles (Chelydra serpentina) downstream of Griffiss Air Force Base in Rome, New York, a known source of AFFF contamination.
View Article and Find Full Text PDFExp Mol Med
January 2025
Section on DNA Repair, Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
RecQ helicases, highly conserved proteins with pivotal roles in DNA replication, DNA repair and homologous recombination, are crucial for maintaining genomic integrity. Mutations in RECQL4 have been associated with various human diseases, including Rothmund-Thomson syndrome. RECQL4 is involved in regulating major DNA repair pathways, such as homologous recombination and nonhomologous end joining (NHEJ).
View Article and Find Full Text PDFSci Rep
January 2025
Department of Veterinary Medicine, University of Teramo, Via Renato Balzarini 1, 64100, Teramo, Italy.
Understanding the molecular mechanisms that confer cold resistance in mammalian cells might be relevant for advancing medical applications. This study aimed to exploit the protective function of Late Embryogenesis Abundant (LEA) proteins, known to provide resistance to low temperatures in extremophiles and plants, by their exogenous expression in mammalian cells, and compare their effects with the well characterized antioxidant, vitamin E.Remarkably, the expression of LEA proteins in mammalian cells exerted cold-protective effect similar to Vitamin E.
View Article and Find Full Text PDFNat Commun
January 2025
European Research Institute for the Biology of Ageing, University Medical Center Groningen, Groningen, Netherlands.
While the effect of amplification-induced oncogene expression in cancer is known, the impact of copy-number gains on "bystander" genes is less understood. We create a comprehensive map of dosage compensation in cancer by integrating expression and copy number profiles from over 8000 tumors in The Cancer Genome Atlas and cell lines from the Cancer Cell Line Encyclopedia. Additionally, we analyze 17 cancer open reading frame screens to identify genes toxic to cancer cells when overexpressed.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!