TY - JOUR AU - Ungvári, Zoltán István AU - Ungvári, Anna Sára AU - Bianchini, Giampaolo AU - Győrffy, Balázs TI - Prognostic significance of a signature based on senescence-related genes in colorectal cancer JF - GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE) J2 - GEROSCIENCE PY - 2024 SN - 2509-2715 DO - 10.1007/s11357-024-01164-6 UR - https://m2.mtmt.hu/api/publication/34825015 ID - 34825015 N1 - Funding Agency and Grant Number: Semmelweis University Funding text: No Statement Available AB - Colorectal cancer, recognized as a quintessential age-related disease, underscores the intricate interplay between aging mechanisms and disease pathogenesis. Cellular senescence, a DNA damage-induced cellular stress response, is characterized by cell cycle arrest, the expression of an inflammatory senescence-associated secretory phenotype, and alterations in extracellular matrix metabolism. It is widely recognized as a fundamental and evolutionarily conserved mechanism of aging. Guided by geroscience principles, which assert that the pathogenesis of age-related diseases involves cellular mechanisms of aging, this study delves into the role of senescence-related genes in colon cancer progression. Leveraging a gene set reflective of senescence-associated pathways, we employed uni- and multivariate Cox proportional hazards survival analysis combined with the determination of the false discovery rate to analyze correlations between gene expression and survival. The integrated database of 1130 colon cancer specimens with available relapse-free survival time and relapse event data from ten independent cohorts provided a robust platform for survival analyses. We identified senescence-related genes associated with differential expression levels linked to shorter survival. Our findings unveil a prognostic signature utilizing cellular senescence-related genes (hazard ratio: 2.73, 95% CI 2.12-3.52, p = 6.4E - 16), offering valuable insights into survival prediction in colon cancer. Multivariate analysis underscored the independence of the senescence-related signature from available epidemiological and pathological variables. This study highlights the potential of senescence-related genes as prognostic biomarkers. Overall, our results underscore the pivotal role of cellular senescence, a fundamental mechanism of aging, in colon cancer progression. LA - English DB - MTMT ER - TY - JOUR AU - Csiszar, Anna AU - Ungvári, Anna Sára AU - Patai, Roland AU - Gulej, Rafal AU - Yabluchanskiy, Andriy AU - Benyó, Zoltán AU - Kovács, Illés AU - Sótonyi, Péter AU - Kirkpartrick, Angelia C AU - Prodan, Calin I AU - Liotta, Eric M AU - Zhang, Xin A AU - Tóth, Péter József AU - Tarantini, Stefano AU - Sorond, Farzaneh A AU - Ungvári, Zoltán István TI - Atherosclerotic burden and cerebral small vessel disease : exploring the link through microvascular aging and cerebral microhemorrhages JF - GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE) J2 - GEROSCIENCE PY - 2024 SN - 2509-2715 DO - 10.1007/s11357-024-01139-7 UR - https://m2.mtmt.hu/api/publication/34804161 ID - 34804161 N1 - * Megosztott szerzőség AB - Cerebral microhemorrhages (CMHs, also known as cerebral microbleeds) are a critical but frequently underestimated aspect of cerebral small vessel disease (CSVD), bearing substantial clinical consequences. Detectable through sensitive neuroimaging techniques, CMHs reveal an extensive pathological landscape. They are prevalent in the aging population, with multiple CMHs often being observed in a given individual. CMHs are closely associated with accelerated cognitive decline and are increasingly recognized as key contributors to the pathogenesis of vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). This review paper delves into the hypothesis that atherosclerosis, a prevalent age-related large vessel disease, extends its pathological influence into the cerebral microcirculation, thereby contributing to the development and progression of CSVD, with a specific focus on CMHs. We explore the concept of vascular aging as a continuum, bridging macrovascular pathologies like atherosclerosis with microvascular abnormalities characteristic of CSVD. We posit that the same risk factors precipitating accelerated aging in large vessels (i.e., atherogenesis), primarily through oxidative stress and inflammatory pathways, similarly instigate accelerated microvascular aging. Accelerated microvascular aging leads to increased microvascular fragility, which in turn predisposes to the formation of CMHs. The presence of hypertension and amyloid pathology further intensifies this process. We comprehensively overview the current body of evidence supporting this interconnected vascular hypothesis. Our review includes an examination of epidemiological data, which provides insights into the prevalence and impact of CMHs in the context of atherosclerosis and CSVD. Furthermore, we explore the shared mechanisms between large vessel aging, atherogenesis, microvascular aging, and CSVD, particularly focusing on how these intertwined processes contribute to the genesis of CMHs. By highlighting the role of vascular aging in the pathophysiology of CMHs, this review seeks to enhance the understanding of CSVD and its links to systemic vascular disorders. Our aim is to provide insights that could inform future therapeutic approaches and research directions in the realm of neurovascular health. LA - English DB - MTMT ER - TY - JOUR AU - Varga, Csaba AU - Springó, Zsolt AU - Koch, M. AU - Prenek, L. AU - Porcsa, L. AU - Bellyei, Szabolcs AU - Rumi, L. AU - Szabó, É. AU - Ungvári, Zoltán István AU - Girán, K. AU - Kiss, I. AU - Pozsgai, É. TI - Predictive factors of basic palliative and hospice care among patients with cancer visiting the emergency department in a Hungarian tertiary care center JF - HELIYON J2 - HELIYON VL - 10 PY - 2024 IS - 8 PG - 11 SN - 2405-8440 DO - 10.1016/j.heliyon.2024.e29348 UR - https://m2.mtmt.hu/api/publication/34803971 ID - 34803971 LA - English DB - MTMT ER - 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 - Petersen, B. AU - Negri, S. AU - Milan, M. AU - Reyff, Z. AU - Ballard, C. AU - Ihuoma, J. AU - Ungvári, Zoltán István AU - Tarantini, Stefano TI - Editorial: Endocrine regulation of aging: impacts of humoral factors and circulating mediators JF - FRONTIERS IN ENDOCRINOLOGY J2 - FRONT ENDOCRINOL VL - 15 PY - 2024 PG - 3 SN - 1664-2392 DO - 10.3389/fendo.2024.1387435 UR - https://m2.mtmt.hu/api/publication/34760823 ID - 34760823 N1 - Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Vascular Cognitive Impairment and Neurodegeneration Program, Department of Neurosurgery, 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 Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Export Date: 6 April 2024 Correspondence Address: Tarantini, S.; Oklahoma Center for Geroscience and Healthy Brain Aging, United States; email: Stefano-tarantini@ouhsc.edu Chemicals/CAS: galectin 3, 208128-56-7; growth hormone, 36992-73-1, 37267-05-3, 66419-50-9, 9002-72-6; nicotinamide adenine dinucleotide, 53-84-9 Funding details: National Institute of General Medical Sciences, NIGMS Funding details: American Heart Association, AHA, CDA941290 Funding details: U54GM104938 Funding details: 1P20GM125528-01A1 Funding details: T32AG052363 Funding details: National Institute on Aging, NIA, K01AG073614, R21AG080775, R03AG070479 Funding text 1: The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the National Institute on Aging (NIA R03AG070479, NIA K01AG073614 and R21AG080775), the American Heart Association (AHA CDA941290), the HEvolution Foundation, the NIA-supported Geroscience Training Program in Oklahoma (T32AG052363), the NIA-supported Oklahoma Nathan Shock Center, and the NIGMS-supported Center of Biomedical Research Excellence (CoBRE) (1P20GM125528-01A1). This research was also supported by the Oklahoma Shared Clinical and Translational Resources (U54GM104938) with an Institutional Development Award (IDeA) from NIGMS. LA - English DB - MTMT ER - TY - JOUR AU - Owens, Cameron D AU - Bonin Pinto, Camila AU - Detwiler, Sam AU - Olay, Lauren AU - Pinaffi-Langley, Ana Clara da C AU - Mukli, Péter AU - Péterfi, Anna AU - Szarvas, Zsófia AU - James, Judith A AU - Galvan, Veronica AU - Tarantini, Stefano AU - Csiszar, Anna AU - Ungvári, Zoltán István AU - Kirkpatrick, Angelia C AU - Prodan, Calin I AU - Yabluchanskiy, Andriy TI - Neurovascular coupling impairment as a mechanism for cognitive deficits in COVID-19 JF - BRAIN COMMUNICATIONS J2 - BRAIN COMMUN VL - 6 PY - 2024 IS - 2 PG - 23 SN - 2632-1297 DO - 10.1093/braincomms/fcae080 UR - https://m2.mtmt.hu/api/publication/34756276 ID - 34756276 N1 - Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, United States Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, 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/Departments of Public Health, Translational Medicine and Physiology, Semmelweis University, Budapest, 1089, Hungary Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, United States Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States Veterans Affairs Medical Center, Oklahoma City, OK 73104, United States The Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States Cardiovascular Section, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, United States Department of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States Export Date: 5 April 2024 Correspondence Address: Yabluchanskiy, A.; Department of Neurosurgery, 975 NE 10th Street, United States; email: andriy-yabluchanskiy@ouhsc.edu AB - Components that comprise our brain parenchymal and cerebrovascular structures provide a homeostatic environment for proper neuronal function to ensure normal cognition. Cerebral insults (e.g. ischaemia, microbleeds and infection) alter cellular structures and physiologic processes within the neurovascular unit and contribute to cognitive dysfunction. COVID-19 has posed significant complications during acute and convalescent stages in multiple organ systems, including the brain. Cognitive impairment is a prevalent complication in COVID-19 patients, irrespective of severity of acute SARS-CoV-2 infection. Moreover, overwhelming evidence from in vitro, preclinical and clinical studies has reported SARS-CoV-2-induced pathologies in components of the neurovascular unit that are associated with cognitive impairment. Neurovascular unit disruption alters the neurovascular coupling response, a critical mechanism that regulates cerebromicrovascular blood flow to meet the energetic demands of locally active neurons. Normal cognitive processing is achieved through the neurovascular coupling response and involves the coordinated action of brain parenchymal cells (i.e. neurons and glia) and cerebrovascular cell types (i.e. endothelia, smooth muscle cells and pericytes). However, current work on COVID-19-induced cognitive impairment has yet to investigate disruption of neurovascular coupling as a causal factor. Hence, in this review, we aim to describe SARS-CoV-2's effects on the neurovascular unit and how they can impact neurovascular coupling and contribute to cognitive decline in acute and convalescent stages of the disease. Additionally, we explore potential therapeutic interventions to mitigate COVID-19-induced cognitive impairment. Given the great impact of cognitive impairment associated with COVID-19 on both individuals and public health, the necessity for a coordinated effort from fundamental scientific research to clinical application becomes imperative. This integrated endeavour is crucial for mitigating the cognitive deficits induced by COVID-19 and its subsequent burden in this especially vulnerable population. 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 - 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 - Hricisák, László AU - Pál, Éva AU - Nagy, Dorina AU - Delank, Max AU - Polycarpou, Andreas AU - Fülöp, Ágnes AU - Sándor, Péter AU - Sótonyi, Péter AU - Ungvári, Zoltán István AU - Benyó, Zoltán TI - NO Deficiency Compromises Inter- and Intrahemispheric Blood Flow Adaptation to Unilateral Carotid Artery Occlusion JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 2 PG - 17 SN - 1661-6596 DO - 10.3390/ijms25020697 UR - https://m2.mtmt.hu/api/publication/34482135 ID - 34482135 N1 - I AB - Carotid artery stenosis (CAS) affects approximately 5–7.5% of older adults and is recognized as a significant risk factor for vascular cognitive impairment (VCI). The impact of CAS on cerebral blood flow (CBF) within the ipsilateral hemisphere relies on the adaptive capabilities of the cerebral microcirculation. In this study, we aimed to test the hypothesis that the impaired availability of nitric oxide (NO) compromises CBF homeostasis after unilateral carotid artery occlusion (CAO). To investigate this, three mouse models exhibiting compromised production of NO were tested: NOS1 knockout, NOS1/3 double knockout, and mice treated with the NO synthesis inhibitor L-NAME. Regional CBF changes following CAO were evaluated using laser-speckle contrast imaging (LSCI). Our findings demonstrated that NOS1 knockout, NOS1/3 double knockout, and L-NAME-treated mice exhibited impaired CBF adaptation to CAO. Furthermore, genetic deficiency of one or two NO synthase isoforms increased the tortuosity of pial collaterals connecting the frontoparietal and temporal regions. In conclusion, our study highlights the significant contribution of NO production to the functional adaptation of cerebrocortical microcirculation to unilateral CAO. We propose that impaired bioavailability of NO contributes to the impaired CBF homeostasis by altering inter- and intrahemispheric blood flow redistribution after unilateral disruption of carotid artery flow. 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 -