EditorialDNA Damage: Health and Longevity

Sharbel Weidner Maluf ,1 Wilner Martínez-López,2 and Juliana da Silva 3

1Laboratory of Genetics, University Hospital, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil2Epigenetics and Genomic Instability Laboratory, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay3Laboratory of Genetic Toxicology, PPGBioSaúde and PPGGTA, Lutheran University of Brazil (ULBRA), Canoas, RS, Brazil

Correspondence should be addressed to Sharbel Weidner Maluf; 0808swm@gmail.com

Received 18 July 2018; Accepted 19 July 2018; Published 13 September 2018

Copyright © 2018 Sharbel Weidner Maluf et al. This is an open access article distributed under the Creative CommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.

The process of aging results in a host of changes at the cellu-lar and molecular levels, which include genomic instability.Over the entire life course, these changes can be seen inunhealthy manifestations, especially in advanced age withits associated functional declines caused by the accumulationof cellular damage, together a diminished ability to repair thisdamage. Most of the time, the results of DNA damageinclude malformations, cancer, aging, and cell death.

The maintenance of genomic stability has been consid-ered, in several studies, as the main factor that leads tohuman longevity. Information that can be extracted fromolder populations that have achieved greater longevity is avaluable source of knowledge that can be used to break downthis complicated network of cellular responses that leads toaging. Y. J. Kim et al. used genomic database of oldest-oldpopulation to understand the association of DNA repair withlongevity in a very interesting review.

Cell homeostasis is the result of a network of biochemicalfactors; failure to maintain this homeostatic balance mayoccur with aging. In addition to endogenous factors, envi-ronmental exposure to stressors can lead to damage accu-mulation anddisease susceptibility. It is important topoint outthat a healthy environment is critical to ensuring healthyhuman populations. Telomeres play a critical role in protect-ing chromosomal end fusions, degradation, abnormal recom-bination, and other detrimental chromosomal events thatlead to increased genomic instability and aging. Optimumtelomere function and length are important for cell prolif-eration and apoptosis. Critically short telomeres initiate

senescence resulting either in apoptosis or cell cycle arrest.Other phenomenon associated with aging is a change inpatterns of epigenetic modifications. Epigenetics is mostcommonly defined as modifications to DNA and DNA pack-aging that do not involve changes to the DNA sequence andthat are potentially transmissible to daughter cells.

V. F. S. Kahl et al. evaluated the effect of dietary intakeand genetic susceptibility polymorphisms in genes on geno-mic and epigenetic instability in individuals exposed to pesti-cides. They showed increased levels of different parameters ofDNA damage, including reduction of telomere length. GlobalDNA methylation was also decreased in farmers. The influ-ence of diet is also discussed in this study, which suggestsan important role of dietary intake and subjects’ genetic sus-ceptibility to xenobiotic-induced damages and epigeneticalterations in tobacco farmers occupationally exposed tomixtures of pesticides. Susceptibility is critical to an under-standing of environmental diseases, including cancer, andmany xenobiotic agents act to alter susceptibility. Unknownindividual susceptibility, inadequate toxicity data, and theunpredictable nature of interaction effects make the imple-mentation of a human biomonitoring assessment for com-plex mixtures of chemicals extremely complicated.

M. Wezyk et al. discuss that epigenetic mechanisms playan important role in the development and progression ofvarious neurodegenerative diseases, including Alzheimer’sdisease. The study reinforces the view that the genetic meth-ylation status in the blood may be a valuable predictor ofmolecular processes occurring in affected tissues.

HindawiOxidative Medicine and Cellular LongevityVolume 2018, Article ID 9701647, 2 pageshttps://doi.org/10.1155/2018/9701647

T. Moriwaki et al. have shown that ATM (mutatedataxia-telangiectasia) induces cell death with autophagy innondividing cells of Caenorhabditis elegans in response toexposure to H2O2. ATM kinase is a master regulator of theDNA damage response and is directly activated by ROS inaddition to DNA double-stranded breaks.

T. R. D. Hamilton et al. discuss that the most acceptedcauses of sperm DNA damage are deleterious actions ofROS, defects in protamination, and apoptosis, as well assperm DNA fragmentation is considered as one of the maincauses of male infertility. They evaluated the effects of heatstress on the chromatin of ejaculated and epididymal spermand the activation of apoptotic pathways in different celltypes in ram testis. The study demonstrated that testicularheat stress increases ram sperm DNA fragmentation withoutchanges in protamination and apoptotic patterns.

R. S. Fortunato et al. show that the H2O2-generatingenzyme DUOX1 plays an important role in maintaininggenomic stability, demonstrating that this enzyme is silencedin breast cancer, using shRNA to knock down its expressionin nontumor cells (MCF12A).

Carcinogenesis is directly related to the prolonged accu-mulation of injuries at different biological levels, which alterthe cells both genetically and biochemically. In each of thesesituations, there is an opportunity for intervention—a chanceto prevent, delay, or stop the gradual march of healthy cellstowards malignancy. A new strategy to reduce its incidencerelates to intervention programs for diet and nutrition, aswell as for the development of pharmacological products thatcould work as chemopreventives. Nonenzymatic antioxi-dants such as ascorbate, tocopherols, carotenoids, and flavo-noids in general, present in diets rich in fruits and vegetables,are important defenses against free radicals, reducing thechances of developing degenerative pathologies.

M. F. C. J. Paz et al. showed persistent increased frequencyof genomic instability in women diagnosed with breast can-cer. The variability of the DNA damage of breast cancerpatients that can be related to diet, from the diagnosis untilthe end of the oncological treatment, demonstratedmore sus-ceptible to oxidative stress. They concluded that early diagno-sis indicates a good prognosis and is fundamental in patientsurvival, being able to signal a less aggressive treatment.

Alkylating agents (AAs) used as chemotherapy are able toinduce alkylation in macromolecules, causing DNA damage,as DNA methylation. C. F. Araujo-Lima et al. evaluate ator-vastatin (AVA) antimutagenic, cytoprotective, and antigeno-toxic potentials against DNA lesions caused by AA. Thisstudy supports the hypothesis that statins can be chemopre-ventive agents, acting as antimutagenic, antigenotoxic, andcytoprotective components, specifically against alkylatingagents of DNA.

A decline in the efficiency of mitochondrial action withage would cause release of higher concentrations of reactiveoxygen. This would be exacerbated by a decline in theeffectiveness of antioxidant defenses or DNA repair path-ways. Recent animal studies have shown that mitochondrialdysfunction initiates and accelerates renal injury in sepsis.Q. Hu et al. evaluated the efficiency of urinary mitochondrialDNA (UmtDNA) as a marker of renal dysfunction during

sepsis-induced acute kidney injury (AKI) and suggested thatUmtDNA may be regarded as a valuable biomarker for theoccurrence of AKI and the development of mitochondria-targeted therapies following sepsis-induced AKI.

Damage to human genomic DNA occurs very frequently,and the vast majority of these damages are successfullyrepaired by mechanisms involving many biochemical factorsthat characterize the DNA damage response (DDR). Onetheory of aging proposes that it results from the accumu-lation of oxidative damage caused by the action of free radi-cals (reactive oxygen species, ROS) on macromoleculessuch as DNA, proteins, and lipids, leading to a loss of func-tion of these molecules. Many studies suggest that ROSparticipate in the pathophysiological mechanism of varioushuman diseases, including Parkinson’s disease, multiple scle-rosis, muscular dystrophy, cataracts, retinopathies, athero-sclerosis, myocardial infarction, ischemia and reperfusionsyndrome, pulmonary emphysema, hepatic cirrhosis, arthri-tis rheumatoid, and various types of cancer. Also in organtransplants and diseases due to radiation, smoking, and pol-lution and in the aging process, ROS play an important role.The results published in this special issue have shown that theparticipation of DNA damage in aging is a topic that involvesmany different factors, which are related to each other form-ing a metabolic network that is being unveiled and that opensa range for new investigations.

Sharbel Weidner MalufWilner Martínez-López

Juliana da Silva

2 Oxidative Medicine and Cellular Longevity

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