TY - JOUR AU - Balasubramanian, Priya AU - Kiss, Tamás AU - Gulej, Rafal AU - Nyúl-Tóth, Ádám AU - Tarantini, Stefano AU - Yabluchanskiy, Andriy AU - Ungvári, Zoltán István AU - Csiszar, Anna TI - Accelerated Aging Induced by an Unhealthy High-Fat Diet: Initial Evidence for the Role of Nrf2 Deficiency and Impaired Stress Resilience in Cellular Senescence JF - NUTRIENTS J2 - NUTRIENTS VL - 16 PY - 2024 IS - 7 PG - 18 SN - 2072-6643 DO - 10.3390/nu16070952 UR - https://m2.mtmt.hu/api/publication/34773870 ID - 34773870 AB - High-fat diets (HFDs) have pervaded modern dietary habits, characterized by their excessive saturated fat content and low nutritional value. Epidemiological studies have compellingly linked HFD consumption to obesity and the development of type 2 diabetes mellitus. Moreover, the synergistic interplay of HFD, obesity, and diabetes expedites the aging process and prematurely fosters age-related diseases. However, the underlying mechanisms driving these associations remain enigmatic. One of the most conspicuous hallmarks of aging is the accumulation of highly inflammatory senescent cells, with mounting evidence implicating increased cellular senescence in the pathogenesis of age-related diseases. Our hypothesis posits that HFD consumption amplifies senescence burden across multiple organs. To scrutinize this hypothesis, we subjected mice to a 6-month HFD regimen, assessing senescence biomarker expression in the liver, white adipose tissue, and the brain. Aging is intrinsically linked to impaired cellular stress resilience, driven by dysfunction in Nrf2-mediated cytoprotective pathways that safeguard cells against oxidative stress-induced senescence. To ascertain whether Nrf2-mediated pathways shield against senescence induction in response to HFD consumption, we explored senescence burden in a novel model of aging: Nrf2-deficient (Nrf2+/−) mice, emulating the aging phenotype. Our initial findings unveiled significant Nrf2 dysfunction in Nrf2+/− mice, mirroring aging-related alterations. HFD led to substantial obesity, hyperglycemia, and impaired insulin sensitivity in both Nrf2+/− and Nrf2+/+ mice. In control mice, HFD primarily heightened senescence burden in white adipose tissue, evidenced by increased Cdkn2a senescence biomarker expression. In Nrf2+/− mice, HFD elicited a significant surge in senescence burden across the liver, white adipose tissue, and the brain. We postulate that HFD-induced augmentation of senescence burden may be a pivotal contributor to accelerated organismal aging and the premature onset of age-related diseases. LA - English DB - MTMT ER - TY - JOUR AU - Miller, L.R. AU - Bickel, M.A. AU - Tarantini, S. AU - Runion, M.E. AU - Matacchiera, Z. AU - Vance, M.L. AU - Hibbs, C. AU - Vaden, H. AU - Nagykaldi, D. AU - Martin, T. AU - Bullen, E.C. AU - Pinckard, J. AU - Kiss, Tamás AU - Howard, E.W. AU - Yabluchanskiy, A. AU - Conley, S.M. TI - IGF1R deficiency in vascular smooth muscle cells impairs myogenic autoregulation and cognition in mice JF - FRONTIERS IN AGING NEUROSCIENCE J2 - FRONT AGING NEUROSCI VL - 16 PY - 2024 PG - 19 SN - 1663-4365 DO - 10.3389/fnagi.2024.1320808 UR - https://m2.mtmt.hu/api/publication/34729965 ID - 34729965 N1 - Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Vascular Cognitive Impairment and Neurodegeneration Program, Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States The Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Division of Comparative Medicine, Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Pediatric Center, Semmelweis University, Budapest, Hungary Eötvös Loránd Research Network and Semmelweis University Cerebrovascular and Neurocognitive Disorders Research Group, Budapest, Hungary Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States Export Date: 5 April 2024 Correspondence Address: Conley, S.M.; Department of Cell Biology, United States; email: Shannon-conley@ouhsc.edu Chemicals/CAS: buprenorphine, 52485-79-7, 53152-21-9 Tradenames: Image Studio version 5.2, LI COR; Odyssey Fc, LI COR; Olympus BX-62, Olympus, United States; QIAcube, Qiagen, United States; RNeasy, Qiagen, United States; thermocycler, Biorad, United States Manufacturers: Biorad, United States; LI COR; Olympus, United States; Qiagen, United States Funding details: T32AG052363 Funding details: P30AG050911 Funding details: U54GM104938 Funding details: National Institutes of Health, NIH, 1P20GM125528, 5P30EY021725-10, 5P30GM122744, K01AG073614, P30CA225520, R01AG070915, R01EY019494, R03AG070479 Funding details: American Heart Association, AHA, AHA941290 Funding details: Presbyterian Health Foundation, PHF Funding details: Oklahoma Center for the Advancement of Science and Technology, OCAST Funding details: Oklahoma Center for Adult Stem Cell Research, OCASCR Funding text 1: The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Institutes of Health (R01AG070915, R03AG070479, K01AG073614, and R01EY019494) including cores supported as part of (1P20GM125528, 5P30EY021725-10, P30CA225520, and 5P30GM122744), American Heart Association (AHA941290), Hevolution Foundation, Oklahoma Shared Clinical and Translational Resources (U54GM104938), Geroscience Training Program in Oklahoma (T32AG052363), the Oklahoma Nathan Shock Center (P30AG050911), Cellular and Molecular GeroScience CoBRE (1P20GM125528), Presbyterian Health Foundation, Oklahoma Center for Adult Stem Cell Research, and the Oklahoma Center for the Advancement of Science and Technology. Funding agencies had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. LA - English DB - MTMT ER - TY - JOUR AU - Miller, L.R. AU - Bickel, M.A. AU - Vance, M.L. AU - Vaden, H. AU - Nagykaldi, D. AU - Nyúl-Tóth, Ádám AU - Bullen, E.C. AU - Gautam, T. AU - Tarantini, Stefano AU - Yabluchanskiy, A. AU - Kiss, Tamás AU - Ungvári, Zoltán István AU - Conley, S.M. TI - Vascular smooth muscle cell-specific Igf1r deficiency exacerbates the development of hypertension-induced cerebral microhemorrhages and gait defects JF - GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE) J2 - GEROSCIENCE VL - 46 PY - 2024 IS - 3 SP - 3481 EP - 3501 PG - 21 SN - 2509-2715 DO - 10.1007/s11357-024-01090-7 UR - https://m2.mtmt.hu/api/publication/34724864 ID - 34724864 N1 - Department of Cell Biology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd, Oklahoma City, OK 73104, United States Currently at: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, United States Vascular Cognitive Impairment and Neurodegeneration Program, Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary The Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Pediatric Center, Semmelweis University, Budapest, Hungary Eötvös Loránd Research Network and Semmelweis University Cerebrovascular and Neurocognitive Disorders Research Group, Budapest, Hungary Export Date: 6 May 2024 Correspondence Address: Conley, S.M.; Department of Cell Biology, 940 Stanton L. Young Blvd, United States; email: Shannon-conley@ouhsc.edu Chemicals/CAS: angiotensin II, 11128-99-7, 68521-88-0; endothelin 1, 117399-94-7; ketamine, 1867-66-9, 6740-88-1, 81771-21-3; nitric oxide, 10102-43-9; somatomedin C, 67763-96-6; tamoxifen, 10540-29-1; xylazine, 23076-35-9, 7361-61-7; Insulin-Like Growth Factor I; Receptor, IGF Type 1 Tradenames: DS-11, DeNovix; Odyssey Fc, LI COR; RNeasy QIAcube, Qiagen, United States; thermocycler, Biorad; VS120-L100-W, Olympus, United States Manufacturers: Applied Biosystems; Biorad; DeNovix; LI COR; Olympus, United States; Qiagen, United States; R and D Systems, United States; Thermo LA - English DB - MTMT ER - TY - JOUR AU - Ungvári, Anna Sára AU - Kiss, Tamás AU - Gulej, R. AU - Tarantini, Stefano AU - Csik, B. AU - Yabluchanskiy, A. AU - Mukli, Péter AU - Csiszar, Anna AU - Harris, M.L. AU - Ungvári, Zoltán István TI - Irradiation-induced hair graying in mice: an experimental model to evaluate the effectiveness of interventions targeting oxidative stress, DNA damage prevention, and cellular senescence JF - GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE) J2 - GEROSCIENCE VL - 46 PY - 2024 IS - 3 SP - 3105 EP - 3122 PG - 18 SN - 2509-2715 DO - 10.1007/s11357-023-01042-7 UR - https://m2.mtmt.hu/api/publication/34500888 ID - 34500888 LA - English DB - MTMT ER - TY - JOUR AU - Kiss, Tamás AU - Ungvári, Anna Sára AU - Gulej, R. AU - Nyúl-Tóth, Ádám AU - Tarantini, Stefano AU - Benyó, Zoltán AU - Csik, B. AU - Yabluchanskiy, A. AU - Mukli, Péter AU - Csiszar, Anna AU - Ungvári, Zoltán István TI - Whole brain irradiation–induced endothelial dysfunction in the mouse brain JF - GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE) J2 - GEROSCIENCE VL - 46 PY - 2024 IS - 1 SP - 531 EP - 541 PG - 11 SN - 2509-2715 DO - 10.1007/s11357-023-00990-4 UR - https://m2.mtmt.hu/api/publication/34391939 ID - 34391939 N1 - Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary First Department of Pediatrics, Semmelweis University, Budapest, Hungary International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Translational Medicine, Semmelweis University, Budapest, Hungary Eötvös Loránd Research Network and Semmelweis University (ELKH-SE) Cerebrovascular and Neurocognitive Disorders Research Group, Budapest, Hungary Department of Public Health, Semmelweis University, Semmelweis University, Budapest, Hungary Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, United States Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Export Date: 22 January 2024 Correspondence Address: Ungvari, A.; Department of Public Health, Hungary; email: ungann2004@gmail.com Funding details: P20GM125528 Funding details: 101004093/ EUniWell/EAC-A02-2019 / EAC-A02-2019-1 Funding details: 135784, RRF-2.3.1-21-2022-00003 Funding details: P30AG050911 Funding details: U54GM104938 Funding details: National Institute on Aging, NIA, K01AG073613, K01AG073614, R01AG055395, R01AG068295, R01AG070915, R03AG070479, RF1AG072295 Funding details: National Cancer Institute, NCI, P30 CA225520, R01CA255840 Funding details: National Institute of General Medical Sciences, NIGMS Funding details: National Institute of Neurological Disorders and Stroke, NINDS, R01NS100782 Funding details: American Heart Association, AHA, AHA CDA941290, AHA834339 Funding details: Presbyterian Health Foundation, PHF Funding details: Oklahoma Center for the Advancement of Science and Technology, OCAST Funding details: Richard S. Reynolds Foundation Funding details: Oklahoma Tobacco Settlement Endowment Trust, TSET, TKP2021-NKTA-47 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFI Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA Funding text 1: Open access funding provided by Semmelweis University. This work was supported by grants from the American Heart Association (ANT: AHA834339) and (ST: AHA CDA941290), the Oklahoma Center for the Advancement of Science and Technology, the National Institute on Aging (RF1AG072295, R01AG055395, R01AG068295; R01AG070915, K01AG073614, K01AG073613, R03AG070479), the National Institute of Neurological Disorders and Stroke (R01NS100782), the National Cancer Institute (R01CA255840), the Oklahoma Shared Clinical and Translational Resources (U54GM104938) with an Institutional Development Award (IDeA) from NIGMS, the Presbyterian Health Foundation, the Reynolds Foundation, the Oklahoma Nathan Shock Center (P30AG050911), and the Cellular and Molecular GeroScience CoBRE (P20GM125528), the NCI Cancer Center Support Grant (P30 CA225520) and the Oklahoma Tobacco Settlement Endowment Trust. TK was supported by project no. TKP2021-NKTA-47, implemented with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-NKTA funding scheme; by funding through the National Cardiovascular Laboratory Program (RRF-2.3.1-21-2022-00003) provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund; project no. 135784 implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the K_20 funding scheme and the European University for Well-Being (EUniWell) program (grant agreement number: 101004093/ EUniWell/EAC-A02-2019 / EAC-A02-2019-1). LA - English DB - MTMT ER - TY - JOUR AU - Dey, A. AU - Pramanik, P.K. AU - Dwivedi, S.K.D. AU - Neizer-Ashun, F. AU - Kiss, Tamás AU - Ganguly, A. AU - Rice, H. AU - Mukherjee, P. AU - Xu, C. AU - Ahmad, M. AU - Csiszar, A. AU - Bhattacharya, R. TI - A role for the cystathionine-β-synthase /H2S axis in astrocyte dysfunction in the aging brain JF - REDOX BIOLOGY J2 - REDOX BIOL VL - 68 PY - 2023 PG - 9 SN - 2213-2317 DO - 10.1016/j.redox.2023.102958 UR - https://m2.mtmt.hu/api/publication/34376788 ID - 34376788 LA - English DB - MTMT ER - TY - GEN AU - Csizek, Zsófia AU - Matyas, Bukva AU - Cintia, Petes AU - Szabó, Attila AU - Kiss, Tamás TI - IN CHILDREN LOW BIRTH WEIGHT MAY CONTRIBUTE TO THE DEVELOPMENT OF SEVERE COVID-19 PY - 2023 UR - https://m2.mtmt.hu/api/publication/34182574 ID - 34182574 N1 - {poszter} LA - English DB - MTMT ER - TY - JOUR AU - Gulej, Rafal AU - Nyúl-Tóth, Ádám AU - Ahire, Chetan AU - DelFavero, Jordan AU - Balasubramanian, Priya AU - Kiss, Tamás AU - Tarantini, Stefano AU - Benyó, Zoltán AU - Pacher, Pál AU - Csik, Boglarka AU - Yabluchanskiy, Andriy AU - Mukli, Péter AU - Kuan-Celarier, Anna AU - Krizbai, István Adorján AU - Campisi, Judith AU - Sonntag, William E. AU - Csiszar, Anna AU - Ungvári, Zoltán István TI - Elimination of senescent cells by treatment with Navitoclax/ABT263 reverses whole brain irradiation-induced blood-brain barrier disruption in the mouse brain JF - GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE) J2 - GEROSCIENCE VL - 45 PY - 2023 IS - 5 SP - 2983 EP - 3002 PG - 20 SN - 2509-2715 DO - 10.1007/s11357-023-00870-x UR - https://m2.mtmt.hu/api/publication/34119854 ID - 34119854 LA - English DB - MTMT ER - TY - JOUR AU - Kiss, Tamás AU - Mir, Mohd Yaqub AU - Stefancsik, Gergely AU - Ganbat, Gantulga AU - Askarova, Aruzhan AU - Monostori, Éva AU - Dulka, Karolina AU - Szebeni, Gábor AU - Nyúl-Tóth, Ádám AU - Csiszar, Anna AU - Légrádi, Ádám TI - Galectin-1 as a marker for microglia activation in the aging brain JF - BRAIN RESEARCH J2 - BRAIN RES VL - 1818 PY - 2023 PG - 13 SN - 0006-8993 DO - 10.1016/j.brainres.2023.148517 UR - https://m2.mtmt.hu/api/publication/34093747 ID - 34093747 N1 - Funding Agency and Grant Number: American Heart Association [GINOP-2.3.2-15-2016-00034, 142877 FK22]; National Research, Development, and Innovation Office (NKFI) , Hungary [AHA834339]; Ministry for Innovation and Technology from the National Research, Development and Innovation Fund; American Heart Association; Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences; [EFOP-3.6.1-16-2016-00008]; [2020-1.1.6-JOVO-2021-00003]; [UNKP-22-5-SZTE-535]; [BO/00582/22/8] Funding text: This work was supported by a grant from EFOP-3.6.1-16-2016-00008 and GINOP-2.3.2-15-2016-00034 grants. ANyT was supported by American Heart Association (AHA834339) . (The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript) . This research was funded by the 2020-1.1.6-JOVO-2021-00003 and 142877 FK22, grant from the National Research, Development, and Innovation Office (NKFI) , Hungary. This work was supported by the UNKP-22-5-SZTE-535 New National Excellence Program (GJS) of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund. This work was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences BO/00582/22/8 (GJS) . AB - Microglia cells, the immune cells residing in the brain, express immune regulatory molecules that have a central role in the manifestation of age-related brain characteristics. Our hypothesis suggests that galectin-1, an anti-inflammatory member of the beta-galactoside-binding lectin family, regulates microglia and neuroinflammation in the aging brain. Through our in-silico analysis, we discovered a subcluster of microglia in the aged mouse brain that exhibited increased expression of galectin-1 mRNA. In our Western blotting experiments, we observed a decrease in galectin-1 protein content in our rat primary cortical cultures over time. Additionally, we found that the presence of lipopolysaccharide, an immune activator, significantly increased the expression of galectin-1 protein in microglial cells. Utilizing flow cytometry, we determined that a portion of the galectin-1 protein was localized on the surface of the microglial cells. As cultivation time increased, we observed a decrease in the expression of activation-coupled molecules in microglial cells, indicating cellular exhaustion. In our mixed rat primary cortical cell cultures, we noted a transition of amoeboid microglial cells labeled with OX42(CD11b/c) to a ramified, branched phenotype during extended cultivation, accompanied by a complete disappearance of galectin-1 expression. By analyzing the transcriptome of a distinct microglial subpopulation in an animal model of aging, we established a correlation between chronological aging and galectin-1 expression. Furthermore, our in vitro study demonstrated that galectin-1 expression is associated with the functional activation state of microglial cells exhibiting specific amoeboid morphological characteristics. Based on our findings, we identify galectin-1 as a marker for microglia activation in the context of aging. LA - English DB - MTMT ER - TY - JOUR AU - Ahire, Chetan AU - Nyúl-Tóth, Ádám AU - DelFavero, Jordan AU - Gulej, Rafal AU - Faakye, Janet A. AU - Tarantini, Stefano AU - Kiss, Tamás AU - Kuan-Celarier, Anna AU - Balasubramanian, Priya AU - Ungvári, Anna Sára AU - Tarantini, Amber AU - Nagaraja, Raghavendra AU - Yan, Feng AU - Tang, Qinggong AU - Mukli, Péter AU - Csípő, Tamás AU - Yabluchanskiy, Andriy AU - Campisi, Judith AU - Ungvári, Zoltán István AU - Csiszar, Anna TI - Accelerated cerebromicrovascular senescence contributes to cognitive decline in a mouse model of paclitaxel (Taxol)-induced chemobrain JF - AGING CELL J2 - AGING CELL VL - 22 PY - 2023 IS - 7 PG - 15 SN - 1474-9718 DO - 10.1111/acel.13832 UR - https://m2.mtmt.hu/api/publication/33989450 ID - 33989450 N1 - * Megosztott szerzőség AB - Chemotherapy-induced cognitive impairment ("chemobrain") is a frequent side-effect in cancer survivors treated with paclitaxel (PTX). The mechanisms responsible for PTX-induced cognitive impairment remain obscure, and there are no effective treatments or prevention strategies. Here, we test the hypothesis that PTX induces endothelial senescence, which impairs microvascular function and contributes to the genesis of cognitive decline. We treated transgenic p16-3MR mice, which allows the detection and selective elimination of senescent cells, with PTX (5 mg/kg/day, 2 cycles; 5 days/cycle). PTX-treated and control mice were tested for spatial memory performance, neurovascular coupling (NVC) responses (whisker-stimulation-induced increases in cerebral blood flow), microvascular density, blood-brain barrier (BBB) permeability and the presence of senescent endothelial cells (by flow cytometry and single-cell transcriptomics) at 6 months post-treatment. PTX induced senescence in endothelial cells, which associated with microvascular rarefaction, NVC dysfunction, BBB disruption, neuroinflammation, and impaired performance on cognitive tasks. To establish a causal relationship between PTX-induced senescence and impaired microvascular functions, senescent cells were depleted from PTX-treated animals (at 3 months post-treatment) by genetic (ganciclovir) or pharmacological (treatment with the senolytic drug ABT263/Navitoclax) means. In PTX treated mice, both treatments effectively eliminated senescent endothelial cells, rescued endothelium-mediated NVC responses and BBB integrity, increased capillarization and improved cognitive performance. Our findings suggest that senolytic treatments can be a promising strategy for preventing chemotherapy-induced cognitive impairment. LA - English DB - MTMT ER -