title: Age dynamics of DNA damage and CpG methylation in the peripheral blood leukocytes of mice.
abstract: Certain types of DNA damage are known to accumulate with age. Here we present the quantitative data describing the extent of the spontaneous DNA damage in 144 SHK mice of various ages. In each animal, we assessed double strand breaks, single strand breaks and alkali-labile sites, as well as amounts of oxidized purines, oxidized pyrimidines and misincorporated uracils. In addition, overall levels of genome DNA methylation were evaluated. The amounts of oxidized pyrimidines were correlated with age in males only, while the amounts of double strand breaks (DSB) in DNA samples were correlated with age in females only (R=0.26; p<0.035). No age-related accumulation of single-strand breaks (SSB) was observed. The hypomethylation of DNA was significant in aging females, but not in aging males. Various types of DNA damage were correlated to each other. In attempt to develop more stable indicator of age-dependent alterations in DNA, the DNA Damage Level Differential (DDLD) indices was developed for comet assaying of peripheral blood leukocytes. As expected, DDLD index was shown to be better correlated with age than any single quantitative measure reflecting certain type of DNA damage. A variability of effectiveness of various kinds of DNA repair in individual animals was larger than expected. This conclusion may have a substantial impact on subsequent studies of the mutagens and other kinds of environmental stressors in animal populations. Nor DDLD neither individual quantitative measures of DNA damage were capable of prediction post-sampling survival time.
authors: Institute of Biology, Komi Science Center of RAS, 28 Kommunisticheskaya st., Syktyvkar 167982, Russia. Electronic address: vellio@yandex.ru.
authors: Ilya
authors: I
authors: Velegzhaninov
authors: Institute of Biology, Komi Science Center of RAS, 28 Kommunisticheskaya st., Syktyvkar 167982, Russia. Electronic address: vera-mezenceva@mail.ru.
authors: Vera
authors: V
authors: Mezenceva
authors: Institute of Biology, Komi Science Center of RAS, 28 Kommunisticheskaya st., Syktyvkar 167982, Russia. Electronic address: olash@list.ru.
authors: Olga
authors: O
authors: Shostal
authors: Moscow Institute of Physics and Technology, 9 Instituitsky per., Dolgoprudny, Moscow Region 141700, Russia; School of Systems Biology, George Mason University (GMU), 4400 University drive, Fairfax, VA 22030, USA; Research Centre for Medical Genetics (RCMG) of RAMS, 1 Moskvorechie str, Moscow, Russia. Electronic address: abaranov@gmu.edu.
authors: Ancha
authors: A
authors: Baranova
authors: Institute of Biology, Komi Science Center of RAS, 28 Kommunisticheskaya st., Syktyvkar 167982, Russia; Syktyvkar State University, 55 Oktyabrsky ave., Syktyvkar 167001, Russia; Moscow Institute of Physics and Technology, 9 Instituitsky per., Dolgoprudny, Moscow Region 141700, Russia; School of Systems Biology, George Mason University (GMU), 4400 University drive, Fairfax, VA 22030, USA; The Vavilov Institute of General Genetics, 3 Gubkina street, Moscow, Russia. Electronic address: amoskalev@ib.komisc.ru.
authors: Alexey
authors: A
authors: Moskalev
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D018899:CpG Islands; D053903:DNA Breaks, Double-Stranded; D019175:DNA Methylation; D005260:Female; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D012727:Sex Characteristics
keywords: Aging; Biomarkers; Comet assay; DNA damage; Hypomethylation of DNA; Mice