@article{MTMT:34773870,
	title = {Accelerated Aging Induced by an Unhealthy High-Fat Diet: Initial Evidence for the Role of Nrf2 Deficiency and Impaired Stress Resilience in Cellular Senescence},
	url = {https://m2.mtmt.hu/api/publication/34773870},
	author = {Balasubramanian, Priya and Kiss, Tamás and Gulej, Rafal and Nyúl-Tóth, Ádám and Tarantini, Stefano and Yabluchanskiy, Andriy and Ungvári, Zoltán István and Csiszar, Anna},
	doi = {10.3390/nu16070952},
	journal-iso = {NUTRIENTS},
	journal = {NUTRIENTS},
	volume = {16},
	unique-id = {34773870},
	abstract = {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.},
	year = {2024},
	eissn = {2072-6643},
	orcid-numbers = {Kiss, Tamás/0000-0001-5339-5227; Gulej, Rafal/0000-0002-9958-707X; Tarantini, Stefano/0000-0001-5627-1430; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:34724864,
	title = {Vascular smooth muscle cell-specific Igf1r deficiency exacerbates the development of hypertension-induced cerebral microhemorrhages and gait defects},
	url = {https://m2.mtmt.hu/api/publication/34724864},
	author = {Miller, L.R. and Bickel, M.A. and Vance, M.L. and Vaden, H. and Nagykaldi, D. and Nyúl-Tóth, Ádám and Bullen, E.C. and Gautam, T. and Tarantini, Stefano and Yabluchanskiy, A. and Kiss, Tamás and Ungvári, Zoltán István and Conley, S.M.},
	doi = {10.1007/s11357-024-01090-7},
	journal-iso = {GEROSCIENCE},
	journal = {GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)},
	volume = {46},
	unique-id = {34724864},
	issn = {2509-2715},
	year = {2024},
	eissn = {2509-2723},
	pages = {3481-3501},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Kiss, Tamás/0000-0001-5339-5227; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:34506904,
	title = {Dimension-based quantification of aging-associated cerebral microvasculature determined by optical coherence tomography and two-photon microscopy},
	url = {https://m2.mtmt.hu/api/publication/34506904},
	author = {Yan, F. and Alhajeri, Z.A. and Nyúl-Tóth, Ádám and Wang, C. and Zhang, Q. and Mercyshalinie, E.R.S. and Delfavero, J. and Ahire, C. and Mutembei, B.M. and Tarantini, S. and Csiszar, Anna and Tang, Q.},
	doi = {10.1002/jbio.202300409},
	journal-iso = {J BIOPHOTONICS},
	journal = {JOURNAL OF BIOPHOTONICS},
	volume = {17},
	unique-id = {34506904},
	issn = {1864-063X},
	year = {2024},
	eissn = {1864-0648}
}

@article{MTMT:34477401,
	title = {Impaired Neurovascular Coupling and Increased Functional Connectivity in the Frontal Cortex Predict Age-Related Cognitive Dysfunction},
	url = {https://m2.mtmt.hu/api/publication/34477401},
	author = {Mukli, Péter and Pinto, Camila B and Owens, Cameron D and Csípő, Tamás and Lipécz, Ágnes and Szarvas, Zsófia and Péterfi, Anna and Langley, Ana Clara da Costa Pinaffi and Hoffmeister, Jordan and Rácz, Frigyes Sámuel and Perry, Jonathan W and Tarantini, Stefano and Nyúl-Tóth, Ádám and Sorond, Farzaneh A and Yang, Yuan and James, Judith A and Kirkpatrick, Angelia C and Prodan, Calin I and Tóth, Péter József and Galindo, Juliette and Gardner, Andrew W and Sonntag, William E and Csiszar, Anna and Ungvári, Zoltán István and Yabluchanskiy, Andriy},
	doi = {10.1002/advs.202303516},
	journal-iso = {ADV SCI},
	journal = {ADVANCED SCIENCE},
	volume = {11},
	unique-id = {34477401},
	abstract = {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.},
	keywords = {Aging; cognitive decline; functional connectivity; Neurovascular coupling; functional near-infrared spectroscopy},
	year = {2024},
	eissn = {2198-3844},
	orcid-numbers = {Mukli, Péter/0000-0003-4355-8103; Szarvas, Zsófia/0000-0002-0022-5053; Rácz, Frigyes Sámuel/0000-0001-9077-498X; Tarantini, Stefano/0000-0001-5627-1430; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:34474845,
	title = {Rejuvenation of cerebromicrovascular function in aged mice through heterochronic parabiosis: insights into neurovascular coupling and the impact of young blood factors},
	url = {https://m2.mtmt.hu/api/publication/34474845},
	author = {Gulej, R. and Nyúl-Tóth, Ádám and Csik, B. and Petersen, B. and Faakye, J. and Negri, S. and Chandragiri, S.S. and Mukli, Péter and Yabluchanskiy, A. and Conley, S. and Huffman, D.M. and Csiszar, Anna and Tarantini, Stefano and Ungvári, Zoltán István},
	doi = {10.1007/s11357-023-01039-2},
	journal-iso = {GEROSCIENCE},
	journal = {GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)},
	volume = {46},
	unique-id = {34474845},
	issn = {2509-2715},
	year = {2024},
	eissn = {2509-2723},
	pages = {327-347},
	orcid-numbers = {Mukli, Péter/0000-0003-4355-8103; Tarantini, Stefano/0000-0001-5627-1430; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:34444878,
	title = {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},
	url = {https://m2.mtmt.hu/api/publication/34444878},
	author = {Gulej, Rafal and Csik, B. and Faakye, J. and Tarantini, Stefano and Shanmugarama, S. and Chandragiri, S.S. and Mukli, P. and Conley, S. and Csiszar, Anna and Ungvári, Zoltán István and Yabluchanskiy, A. and Nyúl-Tóth, Ádám},
	doi = {10.1111/micc.12840},
	journal-iso = {MICROCIRCULATION},
	journal = {MICROCIRCULATION},
	volume = {31},
	unique-id = {34444878},
	issn = {1073-9688},
	year = {2024},
	eissn = {1549-8719},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:34415989,
	title = {Preventing spontaneous cerebral microhemorrhages in aging mice : a novel approach targeting cellular senescence with ABT263/navitoclax},
	url = {https://m2.mtmt.hu/api/publication/34415989},
	author = {Faakye, Janet and Nyúl-Tóth, Ádám and Murányi, Mihály and Gulej, Rafal and Csik, Boglarka and Shanmugarama, Santny and Tarantini, Stefano and Negri, Sharon and Prodan, Calin and Mukli, Peter and Yabluchanskiy, Andriy and Conley, Shannon and Tóth, Péter József and Csiszar, Anna and Ungvári, Zoltán István},
	doi = {10.1007/s11357-023-01024-9},
	journal-iso = {GEROSCIENCE},
	journal = {GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)},
	volume = {46},
	unique-id = {34415989},
	issn = {2509-2715},
	abstract = {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.},
	keywords = {HYPERTENSION; CAPILLARY; cellular senescence; Cerebral microcirculation; ABT263/Navitoclax; Senolytic therapy},
	year = {2024},
	eissn = {2509-2723},
	pages = {21-37},
	orcid-numbers = {Murányi, Mihály/0000-0002-7888-9749; Tarantini, Stefano/0000-0001-5627-1430; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:34391939,
	title = {Whole brain irradiation–induced endothelial dysfunction in the mouse brain},
	url = {https://m2.mtmt.hu/api/publication/34391939},
	author = {Kiss, Tamás and Ungvári, Anna Sára and Gulej, R. and Nyúl-Tóth, Ádám and Tarantini, Stefano and Benyó, Zoltán and Csik, B. and Yabluchanskiy, A. and Mukli, Péter and Csiszar, Anna and Ungvári, Zoltán István},
	doi = {10.1007/s11357-023-00990-4},
	journal-iso = {GEROSCIENCE},
	journal = {GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)},
	volume = {46},
	unique-id = {34391939},
	issn = {2509-2715},
	year = {2024},
	eissn = {2509-2723},
	pages = {531-541},
	orcid-numbers = {Kiss, Tamás/0000-0001-5339-5227; Tarantini, Stefano/0000-0001-5627-1430; Benyó, Zoltán/0000-0001-6015-0359; Mukli, Péter/0000-0003-4355-8103; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:34119854,
	title = {Elimination of senescent cells by treatment with Navitoclax/ABT263 reverses whole brain irradiation-induced blood-brain barrier disruption in the mouse brain},
	url = {https://m2.mtmt.hu/api/publication/34119854},
	author = {Gulej, Rafal and Nyúl-Tóth, Ádám and Ahire, Chetan and DelFavero, Jordan and Balasubramanian, Priya and Kiss, Tamás and Tarantini, Stefano and Benyó, Zoltán and Pacher, Pál and Csik, Boglarka and Yabluchanskiy, Andriy and Mukli, Péter and Kuan-Celarier, Anna and Krizbai, István Adorján and Campisi, Judith and Sonntag, William E. and Csiszar, Anna and Ungvári, Zoltán István},
	doi = {10.1007/s11357-023-00870-x},
	journal-iso = {GEROSCIENCE},
	journal = {GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)},
	volume = {45},
	unique-id = {34119854},
	issn = {2509-2715},
	year = {2023},
	eissn = {2509-2723},
	pages = {2983-3002},
	orcid-numbers = {Kiss, Tamás/0000-0001-5339-5227; Tarantini, Stefano/0000-0001-5627-1430; Benyó, Zoltán/0000-0001-6015-0359; Pacher, Pál/0000-0001-7036-8108; Mukli, Péter/0000-0003-4355-8103; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:34093747,
	title = {Galectin-1 as a marker for microglia activation in the aging brain},
	url = {https://m2.mtmt.hu/api/publication/34093747},
	author = {Kiss, Tamás and Mir, Mohd Yaqub and Stefancsik, Gergely and Ganbat, Gantulga and Askarova, Aruzhan and Monostori, Éva and Dulka, Karolina and Szebeni, Gábor and Nyúl-Tóth, Ádám and Csiszar, Anna and Légrádi, Ádám},
	doi = {10.1016/j.brainres.2023.148517},
	journal-iso = {BRAIN RES},
	journal = {BRAIN RESEARCH},
	volume = {1818},
	unique-id = {34093747},
	issn = {0006-8993},
	abstract = {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.},
	keywords = {Aging; Galectin-1; neuroinflammation; microglia},
	year = {2023},
	eissn = {1872-6240},
	orcid-numbers = {Kiss, Tamás/0000-0001-5339-5227; Stefancsik, Gergely/0000-0002-2098-652X; Monostori, Éva/0000-0002-7442-3562; Dulka, Karolina/0000-0002-7368-8198; Szebeni, Gábor/0000-0002-6998-5632; Légrádi, Ádám/0000-0001-7994-1935}
}