Systems Biology of Aging section

Lymph nodes morphology as predictor natural and premature aging

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Poster (download)

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Gorchakov V.N.¹, Gorchakova O.V.², Kolossova N.G.³, Demchenko G.A.⁴
¹Research Institute of a clinical and experimental Lymphology – branch of Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Science, vgorchak@yandex.ru
²Research Institute of a clinical and experimental Lymphology – branch of Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Science, vgorchak@yandex.ru
³Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Science, kolosova@bionet.nsc.ru
⁴Institute of Physiology of Human and Animals of Committee of Science of the Ministry of Education and Science of the Republic of Kazakhstan, georgiidemchenko@mail.ru

The research purpose is to estimate the structural organization of lymph nodes of different localization at natural (physiological) and premature aging respectively at OXYS and Wistar rats. We used a morphological method of a research. The age-induced changes of lymphoid tissue of Wistar and OXYS rats differ with type of the immune response and morphological variant of lymph nodes structure. The immune response on humoral type is formed in mesenteric and inguinal lymph nodes, and the immune response on cellular type is formed in a tracheobronchial lymph node. We noted reduction of structures of cortical substance, especially lymphoid follicles and a paracortex, and expansion of medullary substance in a lymph node of OXYS rats. Lymph nodes are subject big morphological changes at rats of OXYS, than at old rats of Wistar. Observed changes of structure of lymph nodes of rats of OXYS are a morphological equivalent of premature aging and confirms early decrease of a drainage and immune function of lymph nodes.

Spatial learning as activator of hippocampal neurogenesis during aging and development of Alzheimer\’s disease-like pathology

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Alena Burnyasheva¹, Tatiana Kozlova², Ekaterina Rudnitskaya³, Natalia Stefanova⁴
¹Institute of Cytology and Genetics SB RAS, burnyasheva@bionet.nsc.ru
²Institute of Cytology and Genetics SB RAS, kozlova@bionet.nsc.ru
³Institute of Cytology and Genetics SB RAS, rudnickaya@bionet.nsc.ru
⁴Institute of Cytology and Genetics SB RAS, stefanovan@bionet.nsc.ru

Adult neurogenesis in dentate gyrus (DG) is one of the key mechanisms of neuronal plasticity in hippocampus and plays an important role in cognitive function. However, the consequences of its alteration during healthy aging as well as development of neurodegeneration including AlzheimerвЂ™s disease (AD) remain unclear. It was shown that factors which can activate neurogenesis – such as physical exercises and learning – are able to improve cognitive function. Animal models are useful to clarify the connection between adult neurogenesis and cognitive function during development of AD signs, and OXYS rats are a suitable model for the most common sporadic form of AD. Here we examined effects of spatial learning on neurogenesis in DG of OXYS rats prior to and during manifestation of AD signs. We showed altered reference memory of OXYS rats already at the period prior to neurodegeneration. At the period of active manifestation of AD signs OXYS rats demonstrated altered spatial learning and reversal learning, whereas reference memory was altered only a little. At the period of active amyloid-ОІ accumulation in the brain only reference memory of OXYS rats was altered. Spatial learning resulted in accelerated maturation of immature cells of neuronal and astrocytic cell lineages in DG of OXYS and Wistar rats and decrease of amyloid-ОІ content in aged animals.

MAPK pathways and alphaB-crystallin phosphorylation in brain: a focus on aging and AlzheimerвЂ™s disease

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Natalia Muraleva¹
¹Institute of Cytology and Genetics SB RAS Novosibirsk, Russia, myraleva@bionet.nsc.ru

Accumulation of intracellular damage and protein aggregates is an universal hallmark of aging and accompanies the development of some age-related diseases include AlzheimerвЂ™s disease (AD). Alpha-B-Crystallin (CryaB) as the molecular chaperone contributes maintenance of proteostasis by prevention of aggregation of proteins (e.g. amyloid beta) and enables their correct refolding. CryaB activity is regulated by MAPK signaling pathway (MAPKsp) through its phosphorylation. Nevertheless, the link between changes in MAPK-dependent CryaB phosphorylation with age and the development of AD remains unclear. Here, we examined p38 MAPK- and ERK-dependent phosphorylation of CryaB in the brain of Wistar rats with normal aging and senescence-accelerated OXYS rats at the different stages of the development of AD-like pathology, including the presymptomatic stage.В The most significant changes identified in the p38 MAPK-dependent CryaB phosphorylation. The level of p-Ser59-CryaB in the brain of Wistar rats increased with the age on the background of p38-MAPKsp activation. Similar but more significant changes accompanied the development of AD-like pathology in OXYS rats. The activation of ERK1/2-dependent CryaB phosphorylation (p-Ser45-CryaB) was detected at the early age and at the late stages of AD-like pathology in OXYS, while changes in the ERK1/2 signaling pathway were detected in Wistar rats with age. Thus, alteration of MAPK-dependent phosphorylation CryaB occurs with the normal aging. Manifestation and progression of the signs of the AD occurs against the background of activation of p38MAPK-dependent phosphorylation of CryaB. Activation of EPK-dependent CryaB phosphorylation is characteristic of the preclinical and progressive stage of the AD-like pathology.

Way to longevity: role of antioxidant defense gene polymorphisms in successful adaptation

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Vera Erdman¹, Timur Nasibullin², Ilsia Tuktarova³, Ksenia Danilko⁴, Alisa Matua⁵, Tatiana Viktorova⁶, Olga Mustafina⁷
¹IBG UFRC RAS, danivera@mail.ru
²IBG UFRC RAS, nasibullintr@yandex.ru
³IBG UFRC RAS, iltuk@mail.ru
⁴BSMU, kse-danilko@yandex.ru
⁵SRI EPT ASA, azmatua@mail.ru
⁶BSMU, t_vict@mail.ru
⁷IBG UFRC RAS, anmareg@mail.ru

We carried out the analysis of associations between polymorphic loci of antioxidant defense genes with ethnicity and longevity. We found the interethnic differences in the distribution of allele frequencies of SOD1, SOD2, CAT, NQO1 genes. For reaching longevity SOD1, SOD2, NQO1, GPX1 genes were significant among Russians, SOD2, РЎРђРў genes – among Tatars, MSRA, РЎРђРў genes – among Bashkirs.

Effects of melatonin and SkQ1 long-term treatment during aging and development AMD-like retinopathy

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Poster (download)

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Darya V. Telegina¹, Oyuna S. Kozhevnikova², Anzhela Z. Fursova³
¹ICG SB RAS, Novosibirsk, Russia, telegina@bionet.nsc.ru
²ICG SB RAS, Novosibirsk, Russia, oidopova@bionet.nsc.ru
³ICG SB RAS, Novosibirsk, Russia, anzhellafursova@yandex.ru

Melatonin and antioxidant SkQ1 act like mitochondria-targeted antioxidants, which concentrate in mitochondria at relatively high levels and they may prevent mitochondrial damage during retinal aging and development of age-related retinal disease such as age-related macular degeneration (AMD). However, detailed effects of melatonin and SkQ1 on the biochemical mechanisms underlying therapeutic effect of these drugs during retinal aging and AMD progression remain unclear.В Using Wistar rats with normal aging process and senescence-accelerated OXYS rats, which spontaneously develop a phenotype similar to human age-related disorders including AMD-like retinopathy, we found that treatment of SkQ1 and melatonin decreased the incidence and severity of retinopathy in OXYS rats. In Wistar rats, which do not naturally develop retinopathy, ophthalmoscopic inspections did not reveal pathological alterations in the retina of melatonin and SkQ1-treated rats. SkQ1 decreased p62/SQSTM1 protein but not mRNA levels in both OXYS and Wistar rat\’s retinas as compared of control rats. We observed reduced level of VDAC1 and increased level of glutaminase by long-term treatment of melatonin and SkQ1 in retina of Wistar rats but not OXYS rats. Taken together, our data indicated that long-term treatment of melatonin and mitochondria-targeted antioxidant SkQ1 may retard an age-related decline in the adaptability of retinal cells and may be considered as a strategy to slow down AMD. At the same time effects of melatonin and SkQ1 on molecular events may be different depending on genotype and disease.

Possibility to use divergent tasks for baseline alpha rhythm modulation in older adults.

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Evgeniya Privodnova¹, Nina Volf², Victoriya Bilik³, Ekaterina Merculova⁴
¹Scientific Research Institute of Physiology and Basic Medicine, privodnovaeu@physiol.ru
²Scientific Research Institute of Physiology and Basic Medicine, volf@physiol.ru
³Scientific Research Institute of Physiology and Basic Medicine, v.bilik@mail.ru
⁴Scientific Research Institute of Physiology and Basic Medicine, merkaterine@gmail.com

Findings reliably revealed that alpha power attenuates in aging whereas distractibility tends to increase. Given the causal link between alpha power and inhibition capacity in aged people, enhancement of baseline alpha power may have positive effect on cognition. Based on robust evidence of alpha power enhancement during divergent thinking, we suggested that divergent tasks might be candidate cognitive activity for modulation of resting state alpha rhythm. We investigated the changes in baseline upper alpha rhythm following visual and verbal divergent thinking training session in 30 older adults (64.2В±6 years). 52-channel EEG was registered prior to, during and after session. Upper alpha power was calculated via Fourier transform; current source density (CSD) and statistical nonparametric mapping were performed using LORETA. Analysis of both power and CSD revealed alpha increases from pre-training to post-training interval, with maximum difference in Superior Parietal lobule (region of interest, ROI). CSD estimates during verbal task did not differ from pre-training alpha activity. CSD during visual task performance was higher than at pre-training interval and than during verbal task performance. The spatial pattern of alpha CSD increase during visual task performance matched spatial pattern of CSD increase in post-training activity. Moreover, measures of ROI in visual task performance positively correlated with measures of ROI in post-training interval. The findings are in favor for notion, that divergent thinking session may be viewed as a kind of cognitive activity resulted in alpha power increase in older adults. Visual divergent task performance made crucial impact in this post-training alpha rhythm modulation.

Search for single nucleotide polymorphisms (SNPs) associated with hypertension in the genome of senescence-accelerated OXYS rats

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Poster (download)

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Vasiliy A. Devyatkin¹, Natalia A. Muraleva², Olga E. Redina³, Nataliya Kolosova⁴
¹Institute of Cytology and Genetics SB RAS, devyatkin@bionet.nsc.ru
²Institute of Cytology and Genetics SB RAS, myraleva@bionet.nsc.ru
³Institute of Cytology and Genetics SB RAS, oredina@bionet.nsc.ru
⁴Institute of Cytology and Genetics SB RAS, Nnnnn80@ngs.ru

Aging is a risk factor for many diseases, but the likelihood of developing with age also depends on genetic factors, environmental conditions, lifestyle, and the presence of other pathologies. The OXYS rat strain (ICG SB RAS) is a unique model for studying the mechanisms of aging, as already at an early age these animals develop a whole complex of age-dependent diseases, including cataracts, retinopathy, osteoporosis, hypertension and Alzheimer’s-like pathology. Although hypertension has risk factors typical of age-related diseases, it itself is a risk factor for many other pathologies. However, the complex senile phenotype does not appear in other hypertensive models, even with higher blood pressure. The aim of this study was, based on the results of RNA-Seq, the search for single nucleotide polymorphisms that could contribute to the development of hypertension in OXYS rats with accelerated aging. We found that OXYS rats are genetically far from other strains and presumably have their own bases for the development of hypertension, which may determine the absence of the senile phenotype of OXYS rats in hypertensive rat strains.

Age-related difference in use-dependent plasticity after divergent thinking session matches posterior-anterior shift in aging (PASA) model.

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Poster (download)

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Evgeniya Privodnova¹, Nina Volf², Ekaterina Merculova³, Dariya Bazovkina⁴
¹Scientific Research Institute of Physiology and Basic Medicine, privodnovaeu@physiol.ru
²Scientific Research Institute of Physiology and Basic Medicine, volf@physiol.ru
³Scientific Research Institute of Physiology and Basic Medicine, merkaterine@gmail.com
⁴Scientific Research Institute of Physiology and Basic Medicine, daryabazovkina@gmail.com

Repetitive cognitive activity has the potential to improve cognitive functioning through neuroplasticity. Despite evidence for task-specific traces after task performance in young adults, age differences of experience-related neuroplasticity remains understudied. Common patterns of age-related changes in brain activity across a variety of cognitive functions suggest the hemispheric asymmetry reduction in older adults (HAROLD) and the posterior-to-anterior shift in aging (PASA). We can expect that those models appear as age specificity of experience-related neuroplasticity. The aim of the current study was to investigate the age-related specificity in use-dependent changes between pre-training and post-training baseline alpha EEG rhythm measures. 31 younger (Mean age = 21.3) and 30 older adults (Mean age=64.2) underwent a divergent thinking training session with concomitant 52-channel EEG registration. Upper alpha power was calculated via Fourier transform; current source density estimates and statistical nonparametric mapping were calculated via LORETA. Alpha power increased from baseline to post-session interval in the both age groups, indicating use-dependent plasticity. The anterior-posterior gradient (posterior>anterior) of alpha power increases from baseline to post-session interval in the left hemisphere was more pronounced in younger adults, than in older. Use-dependent plasticity has the same pattern of age differences as PASA postulates, that is, decrease in posterior coupled with increase in anterior areas. The results emphasize that PASA model reflects a global age-associated shift in brain function.

Calorie Restriction in Gerontological Experiments on Cell Cultures

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Poster (download)

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Galina V. Morgunova¹, Alexander N. Khokhlov²
¹Evolutionary Cytogerontology Sector, School of Biology, Lomonosov Moscow State University, Moscow, Russian Federation, morgunova@mail.bio.msu.ru
²Evolutionary Cytogerontology Sector, School of Biology, Lomonosov Moscow State University, Moscow, Russian Federation, khokhlov@mail.bio.msu.ru

Lifespan can be increased by the calorie restriction. However, it is not entirely clear whether this effect is manifested at the cellular level. Recently, it has been shown that calorie restriction extends the lifespan of yeast. We conduct similar experiments on mammalian cell cultures.