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 - 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 LA - English DB - MTMT ER - TY - JOUR AU - Yan, F. AU - Alhajeri, Z.A. AU - Nyúl-Tóth, Ádám AU - Wang, C. AU - Zhang, Q. AU - Mercyshalinie, E.R.S. AU - Delfavero, J. AU - Ahire, C. AU - Mutembei, B.M. AU - Tarantini, S. AU - Csiszar, Anna AU - Tang, Q. TI - Dimension-based quantification of aging-associated cerebral microvasculature determined by optical coherence tomography and two-photon microscopy JF - JOURNAL OF BIOPHOTONICS J2 - J BIOPHOTONICS VL - 17 PY - 2024 IS - 3 PG - 14 SN - 1864-063X DO - 10.1002/jbio.202300409 UR - https://m2.mtmt.hu/api/publication/34506904 ID - 34506904 N1 - Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK, United States 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 International Training Program in Geroscience, Institute of Biophysics, Biological Research Centre, Eötvös Loránd Research Network, Szeged, Hungary Stephenson Cancer Center, 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 Translational Medicine, Semmelweis University, Budapest, Hungary Institute for Biomedical Engineering, Science, and Technology (IBEST), University of Oklahoma, Norman, OK, United States Cited By :1 Export Date: 6 April 2024 Correspondence Address: Tang, Q.; Stephenson School of Biomedical Engineering, United States; email: qtang@ou.edu Funding details: National Science Foundation, NSF, 2238648, OIA‐2132161 Funding details: National Science Foundation, NSF Funding details: National Institutes of Health, NIH, 5U01HL152410‐04, R01CA255840, R01DK133717 Funding details: National Institutes of Health, NIH Funding details: American Cancer Society, ACS Funding details: National Cancer Institute, NCI Funding details: National Institute of General Medical Sciences, NIGMS, P20GM103639, U54GM104938 Funding details: National Institute of General Medical Sciences, NIGMS Funding details: University of Oklahoma, OU, IRG‐19‐142‐01 Funding details: University of Oklahoma, OU Funding details: University of Oklahoma Health Sciences Center, OUHSC, P30CA225520 Funding details: University of Oklahoma Health Sciences Center, OUHSC Funding details: Oklahoma Center for the Advancement of Science and Technology, OCAST, HR23‐071, P20 GM135009 Funding details: Oklahoma Center for the Advancement of Science and Technology, OCAST Funding text 1: This work was supported by grants from the University of Oklahoma Health Sciences Center (P30CA225520), Faculty Investment Program from University of Oklahoma, Institutional Research Grant number IRG‐19‐142‐01 from the American Cancer Society, National Science Foundation (OIA‐2132161, 2238648), National Institute of Health (R01DK133717, R01CA255840, 5U01HL152410‐04), Oklahoma Shared Clinical and Translational Resources (NIGMS U54GM104938), Oklahoma Center for the Advancement of Science and Technology (HR23‐071), and the medical imaging COBRE (P20 GM135009). Histology service provided by the Tissue Pathology Shared Resource was supported in part by the National Institute of General Medical Sciences COBRE Grant P20GM103639 and National Cancer Institute Grant P30CA225520 of the National Institutes of Health. American Heart Association (ANT: AHA834339), the Oklahoma Center for the Advancement of Science and Technology, the National Institute on Aging (RF1AG072295, R01AG055395, R01AG068295; R01AG070915, K01AG073614), the National Institute of Neurological Disorders and Stroke (R01NS100782). Financial support was provided by the OU Libraries' Open Access Fund. LA - English DB - MTMT ER - TY - JOUR AU - Mukli, Péter AU - Pinto, Camila B AU - Owens, Cameron D AU - Csípő, Tamás AU - Lipécz, Ágnes AU - Szarvas, Zsófia AU - Péterfi, Anna AU - Langley, Ana Clara da Costa Pinaffi AU - Hoffmeister, Jordan AU - Rácz, Frigyes Sámuel AU - Perry, Jonathan W AU - Tarantini, Stefano AU - Nyúl-Tóth, Ádám AU - Sorond, Farzaneh A AU - Yang, Yuan AU - James, Judith A AU - Kirkpatrick, Angelia C AU - Prodan, Calin I AU - Tóth, Péter József AU - Galindo, Juliette AU - Gardner, Andrew W AU - Sonntag, William E AU - Csiszar, Anna AU - Ungvári, Zoltán István AU - Yabluchanskiy, Andriy TI - Impaired Neurovascular Coupling and Increased Functional Connectivity in the Frontal Cortex Predict Age-Related Cognitive Dysfunction JF - ADVANCED SCIENCE J2 - ADV SCI VL - 11 PY - 2024 IS - 10 PG - 18 SN - 2198-3844 DO - 10.1002/advs.202303516 UR - https://m2.mtmt.hu/api/publication/34477401 ID - 34477401 AB - Impaired cerebrovascular function contributes to the genesis of age-related cognitive decline. In this study, the hypothesis is tested that impairments in neurovascular coupling (NVC) responses and brain network function predict cognitive dysfunction in older adults. Cerebromicrovascular and working memory function of healthy young (n = 21, 33.2±7.0 years) and aged (n = 30, 75.9±6.9 years) participants are assessed. To determine NVC responses and functional connectivity (FC) during a working memory (n-back) paradigm, oxy- and deoxyhemoglobin concentration changes from the frontal cortex using functional near-infrared spectroscopy are recorded. NVC responses are significantly impaired during the 2-back task in aged participants, while the frontal networks are characterized by higher local and global connection strength, and dynamic FC (p < 0.05). Both impaired NVC and increased FC correlate with age-related decline in accuracy during the 2-back task. These findings suggest that task-related brain states in older adults require stronger functional connections to compensate for the attenuated NVC responses associated with working memory load. LA - English DB - MTMT ER - TY - JOUR AU - Gulej, R. AU - Nyúl-Tóth, Ádám AU - Csik, B. AU - Petersen, B. AU - Faakye, J. AU - Negri, S. AU - Chandragiri, S.S. AU - Mukli, Péter AU - Yabluchanskiy, A. AU - Conley, S. AU - Huffman, D.M. AU - Csiszar, Anna AU - Tarantini, Stefano AU - Ungvári, Zoltán István TI - Rejuvenation of cerebromicrovascular function in aged mice through heterochronic parabiosis: insights into neurovascular coupling and the impact of young blood factors JF - GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE) J2 - GEROSCIENCE VL - 46 PY - 2024 SP - 327 EP - 347 PG - 21 SN - 2509-2715 DO - 10.1007/s11357-023-01039-2 UR - https://m2.mtmt.hu/api/publication/34474845 ID - 34474845 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 Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, United States Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, United States Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, United States International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Translational Medicine, Semmelweis University, Budapest, Hungary Export Date: 19 March 2024 Correspondence Address: Ungvari, Z.; Vascular Cognitive Impairment, United States; email: zoltan-ungvari@ouhsc.edu 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, 916225, AHA CDA941290, AHA834339 Funding details: Presbyterian Health Foundation, PHF Funding details: University of Oklahoma Health Sciences Center, OUHSC 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, P30AG038072, TKP2021-NKTA-47 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFI Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA Funding text 1: We sincerely thank the Division of Comparative Medicine team at the University of Oklahoma Health Sciences Center for their invaluable support in supervising animal care and sharing their extensive expertise. Special recognition is extended to Dr. Shawn Lane, DVM, for his invaluable guidance and expertise in surgical and postsurgical care. We are grateful to Dr. Wendy Williams, DVM, for her instrumental role in designing appropriate pre- and postsurgical treatments. We also acknowledge Ms. Carlye Yancey, BS, for her exceptional animal husbandry knowledge and contributions to parabiosis housing. Furthermore, we wish to express our gratitude to Mr. Chad Cunningham, Electronic & Instrument Shop Supervisor Building Manager of the University of Oklahoma’ s Department of Physics and Engineering for his essential assistance in fabricating the parabiont-adjusted components of the stereotactic frame, which was instrumental in facilitating simultaneous measurements of neurovascular coupling in parabionts. Funding text 2: This work was supported by grants from the American Heart Association (R.G.: 916225, ANT: AHA834339, and S.T.: 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. ANT was supported by Project no. DMH is supported by P30AG038072. 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). The funding sources 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. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the American Heart Association, or the Presbyterian Health Foundation. The 3.5 version of ChatGPT, developed by OpenAI, was used as a language tool to refine our writing, enhancing the clarity of our work. LA - English DB - MTMT ER - TY - JOUR AU - Gulej, Rafal AU - Csik, B. AU - Faakye, J. AU - Tarantini, Stefano AU - Shanmugarama, S. AU - Chandragiri, S.S. AU - Mukli, P. AU - Conley, S. AU - Csiszar, Anna AU - Ungvári, Zoltán István AU - Yabluchanskiy, A. AU - Nyúl-Tóth, Ádám TI - Endothelial deficiency of insulin-like growth factor-1 receptor leads to blood–brain barrier disruption and accelerated endothelial senescence in mice, mimicking aspects of the brain aging phenotype JF - MICROCIRCULATION J2 - MICROCIRCULATION VL - 31 PY - 2024 IS - 2 PG - 13 SN - 1073-9688 DO - 10.1111/micc.12840 UR - https://m2.mtmt.hu/api/publication/34444878 ID - 34444878 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 Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, United States Department of Cell Biology, 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 Translational Medicine, Semmelweis University, Budapest, Hungary Export Date: 18 March 2024 CODEN: MROCE Correspondence Address: Yabluchanskiy, A.; Department of Neurosurgery, United States; email: andriy-yabluchanskiy@ouhsc.edu Correspondence Address: Nyúl-Tóth, Á.; Vascular Cognitive Impairment, United States; email: adam-nyultoth@ouhsc.edu Chemicals/CAS: somatomedin C, 67763-96-6; Insulin-Like Growth Factor I; Insulin-Like Peptides LA - English DB - MTMT ER - TY - JOUR AU - Faakye, Janet AU - Nyúl-Tóth, Ádám AU - Murányi, Mihály AU - Gulej, Rafal AU - Csik, Boglarka AU - Shanmugarama, Santny AU - Tarantini, Stefano AU - Negri, Sharon AU - Prodan, Calin AU - Mukli, Peter AU - Yabluchanskiy, Andriy AU - Conley, Shannon AU - Tóth, Péter József AU - Csiszar, Anna AU - Ungvári, Zoltán István TI - Preventing spontaneous cerebral microhemorrhages in aging mice : a novel approach targeting cellular senescence with ABT263/navitoclax JF - GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE) J2 - GEROSCIENCE VL - 46 PY - 2024 SP - 21 EP - 37 PG - 17 SN - 2509-2715 DO - 10.1007/s11357-023-01024-9 UR - https://m2.mtmt.hu/api/publication/34415989 ID - 34415989 AB - Emerging evidence from both clinical and preclinical studies underscores the role of aging in potentiating the detrimental effects of hypertension on cerebral microhemorrhages (CMHs, or cerebral microbleeds). CMHs progressively impair neuronal function and contribute to the development of vascular cognitive impairment and dementia. There is growing evidence showing accumulation of senescent cells within the cerebral microvasculature during aging, which detrimentally affects cerebromicrovascular function and overall brain health. We postulated that this build-up of senescent cells renders the aged cerebral microvasculature more vulnerable, and consequently, more susceptible to CMHs. To investigate the role of cellular senescence in CMHs' pathogenesis, we subjected aged mice, both with and without pre-treatment with the senolytic agent ABT263/Navitoclax, and young control mice to hypertension via angiotensin-II and L-NAME administration. The aged cohort exhibited a markedly earlier onset, heightened incidence, and exacerbated neurological consequences of CMHs compared to their younger counterparts. This was evidenced through neurological examinations, gait analysis, and histological assessments of CMHs in brain sections. Notably, the senolytic pre-treatment wielded considerable cerebromicrovascular protection, effectively delaying the onset, mitigating the incidence, and diminishing the severity of CMHs. These findings hint at the potential of senolytic interventions as a viable therapeutic avenue to preempt or alleviate the consequences of CMHs linked to aging, by counteracting the deleterious effects of senescence on brain microvasculature. 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 - 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 -