The role of DNA damage and repair in aging through the prism of Koch-like criteria

Moskalev, Alexey; Shaposhnikov, Mikhail; Plyusnina, Ekaterina; Zhavoronkov, Alex; Budovsky, Arie; Yanai, Hagai; Fraifeld, Vadim E.

doi:10.1016/j.arr.2012.02.001

Cited by 309 publications

(230 citation statements)

References 261 publications

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“…Human aging is a complex process that has been linked to dysregulation of numerous cellular and molecular processes, including shortened telomere length (Harley et al ., 1990), altered DNA damage response (Moskalev et al ., 2013), loss of protein homeostasis (Tomaru et al ., 2012), cellular senescence (Childs et al ., 2015), and mitochondrial dysfunction (Green et al ., 2011). Those cellular and molecular processes can lead to a variety of diseases including cancer, cardiovascular disease, and neurological disease, as well as an increased risk of mortality (Fontana et al ., 2010; López‐Otín et al ., 2013).…”

Section: Introductionmentioning

confidence: 99%

Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits

et al. 2017

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SummaryRecent studies provide evidence of correlations of DNA methylation and expression of protein‐coding genes with human aging. The relations of microRNA expression with age and age‐related clinical outcomes have not been characterized thoroughly. We explored associations of age with whole‐blood microRNA expression in 5221 adults and identified 127 microRNAs that were differentially expressed by age at P < 3.3 × 10−4 (Bonferroni‐corrected). Most microRNAs were underexpressed in older individuals. Integrative analysis of microRNA and mRNA expression revealed changes in age‐associated mRNA expression possibly driven by age‐associated microRNAs in pathways that involve RNA processing, translation, and immune function. We fitted a linear model to predict ‘microRNA age’ that incorporated expression levels of 80 microRNAs. MicroRNA age correlated modestly with predicted age from DNA methylation (r = 0.3) and mRNA expression (r = 0.2), suggesting that microRNA age may complement mRNA and epigenetic age prediction models. We used the difference between microRNA age and chronological age as a biomarker of accelerated aging (Δage) and found that Δage was associated with all‐cause mortality (hazards ratio 1.1 per year difference, P = 4.2 × 10−5 adjusted for sex and chronological age). Additionally, Δage was associated with coronary heart disease, hypertension, blood pressure, and glucose levels. In conclusion, we constructed a microRNA age prediction model based on whole‐blood microRNA expression profiling. Age‐associated microRNAs and their targets have potential utility to detect accelerated aging and to predict risks for age‐related diseases.

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Section: Introductionmentioning

confidence: 99%

Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits

et al. 2017

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“…Retrotransposon sequences can comprise up to 30-80% of eukaryotic genomes, and cells commonly inhibit retrotransposon expression and mobility through use of repressive chromatin marks and/or post-transcriptional silencing mechanisms (Slotkin and Martienssen 2007). Changes in chromatin and genome instability are observed with aging, and recent work is demonstrating that the regulation and mobility of retrotransposons also changes during aging (Moskalev et al 2013;Wood and Helfand 2013). Increased expression of retrotransposons with age has been observed in gonads of Caenorhabditis elegans, brains of Drosophila melanogaster, somatic tissues in mice, normal human cells grown ex vivo, and in yeast mother cells (Wang et al 2011;Dennis et al 2012;De Cecco et al 2013a,b;Li et al 2013;Hu et al 2014).…”

mentioning

confidence: 99%

Extension of Saccharomyces paradoxus Chronological Lifespan by Retrotransposons in Certain Media Conditions Is Associated with Changes in Reactive Oxygen Species

VanHoute

Maxwell

2014

Genetics

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Retrotransposons are mobile DNA elements present throughout eukaryotic genomes that can cause mutations and genome rearrangements when they replicate through reverse transcription. Increased expression and/or mobility of retrotransposons has been correlated with aging in yeast, Caenorhabditis elegans, Drosophila melanogaster, and mammals. The many copies of retrotransposons in humans and various model organisms complicate further pursuit of this relationship. The Saccharomyces cerevisiae Ty1 retrotransposon was introduced into a strain of S. paradoxus that completely lacks retrotransposons to compare chronological lifespans (CLSs) of yeast strains with zero, low, or high Ty1 copy number. Yeast chronological lifespan reflects the progressive loss of cell viability in a nondividing state. Chronological lifespans for the strains were not different in rich medium, but were extended in high Ty1 copy-number strains in synthetic medium and in rich medium containing a low dose of hydroxyurea (HU), an agent that depletes deoxynucleoside triphosphates. Lifespan extension was not strongly correlated with Ty1 mobility or mutation rates for a representative gene. Buffering deoxynucleoside triphosphate levels with threonine supplementation did not substantially affect this lifespan extension, and no substantial differences in cell cycle arrest in the nondividing cells were observed. Lifespan extension was correlated with reduced reactive oxygen species during early stationary phase in high Ty1 copy strains, and antioxidant treatment allowed the zero Ty1 copy strain to live as long as high Ty1 copy-number strains in rich medium with hydroxyurea. This exceptional yeast system has identified an unexpected longevity-promoting role for retrotransposons that may yield novel insights into mechanisms regulating lifespan.

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“…Известно, что повреждения ДНК могут индуцировать опухолеобразо-вание [38] и способствуют старению [39]. Кроме того, геномный стресс в клетках костного мозга может при-водить к снижению гематопоэтической и иммунной фун-кций [40].…”

Section: Discussionunclassified

Predator odor induces genome instability in the mouse bone marrow cells

Glinin

Сергеевич²,

Starshova

et al. 2017

Ecological genetics

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Background. Long coevolution of prey and predator species of mammals creates specific mechanisms of their interaction, e. g. prey’s innate behavior aversive to the predator odor. However, little is known about genetic responses in the prey organism. We assessed genome instability of the bone marrow cells in mice affected by the cat’s odor influence, and proposed pathway of such action. Materials and methods. CBA mouse males were exposed to volatiles from adult cat urine for 2 or 24 hours. To estimate the genetic effect, ana-telophase method of chromosome aberration analysis and comet assay were used. The level of corticosterone was also measured after the exposure for 30 or 60 minutes. Results. The exposure to cat’s urine volatiles for 2 hours induced damage of DNA in bone marrow cells of the mouse males as was shown by the DNA comet analysis. The exposure for 24 hours elevated the frequency of chromosome aberrations in mitotically dividing cells at ana-telophase stage. No significant changes were found in the level of corticosterone in the peripheral blood. Conclusion. We have shown that volatile chemosignals from predator’s urine induce genomic instability in bone marrow cells of a prey. The hormonal pathway of such influence is still unknown. Intraorganismic paths leading to genome damage are discussed as well as far consequences of discovered effects.

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The role of DNA damage and repair in aging through the prism of Koch-like criteria

Cited by 309 publications

References 261 publications

Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits

Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits

Extension of Saccharomyces paradoxus Chronological Lifespan by Retrotransposons in Certain Media Conditions Is Associated with Changes in Reactive Oxygen Species

Predator odor induces genome instability in the mouse bone marrow cells

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