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001-es BibID:	BIBFORM099929
035-os BibID:	(WOS)000531041500024 (Scopus)85082710654
Első szerző:	Kiss Tamás (vegyész)
Cím:	Circulating anti-geronic factors from heterochonic parabionts promote vascular rejuvenation in aged mice : transcriptional footprint of mitochondrial protection, attenuation of oxidative stress, and rescue of endothelial function by young blood / Kiss Tamas, Tarantini Stefano, Csipo Tamas, Balasubramanian Priya, Nyúl-Tóth Ádám, Yabluchanskiy Andriy, Wren Jonathan D., Garman Lori, Huffman Derek M., Csiszar Anna, Ungvari Zoltan
Dátum:	2020
ISSN:	2509-2715 2509-2723
Megjegyzések:	Aging-induced functional and phenotypic alterations of the vasculature (e.g., endothelial dysfunction, oxidative stress) have a central role in morbidity and mortality of older adults. It has become apparent in recent years that cell autonomous mechanisms alone are inadequate to explain all aspects of vascular aging. The present study was designed to test the hypothesis that age-related changes in circulating anti-geronic factors contribute to the regulation of vascular aging processes in a non-cell autonomous manner. To test this hypothesis, through heterochronic parabiosis we determined the extent, if any, to which endothelial function, vascular production of ROS, and shifts in the vascular transcriptome (RNA-seq) are modulated by the systemic environment. We found that in aortas isolated from isochronic parabiont aged (20-month-old) C57BL/6 mice [A-(A); parabiosis for 8 weeks] acetylcholine-induced endothelium-dependent relaxation was impaired and ROS production (dihydroethidium fluorescence) was increased as compared with those in aortas from young isochronic parabiont (6-month-old) mice [Y-(Y)]. The presence of young blood derived from young parabionts significantly improved endothelium-dependent vasorelaxation and attenuated ROS production in vessels of heterochronic parabiont aged [A-(Y)] mice. In aortas derived from heterochronic parabiont young [Y-(A)] mice, acetylcholine-induced relaxation and ROS production were comparable with those in aortas derived from Y-(Y) mice. Using RNA-seq we assessed transcriptomic changes in the aortic arch associated with aging and heterochronic parabiosis. We identified 347 differentially expressed genes in A-(A) animals compared with Y-(Y) controls. We have identified 212 discordant genes, whose expression levels differed in the aged phenotype, but have shifted back toward the young phenotype by the presence of young blood in aged A-(Y) animals. Pathway analysis shows that vascular protective effects mediated by young blood-regulated genes include mitochondrial rejuvenation. In conclusion, a relatively short-term exposure to young blood can rescue vascular aging phenotypes, including attenuation of oxidative stress, mitochondrial rejuvenation, and improved endothelial function. Our findings provide additional evidence supporting the significant plasticity of vascular aging and evidence for the existence of anti-geronic factors capable of exerting rejuvenating effects on the aging vasculature.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	GeroScience. - 42 : 2 (2020), p. 727-748. -
További szerzők:	Tarantini, Stefano Csípő Tamás (1990-) Balasubramanian, Priya Nyúl-Tóth Ádám Yabluchanskiy, Andriy Wren, Jonathan D. Garman, Lori Huffman, Derek M. Csiszár Anna Ungvári Zoltán
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM099926
035-os BibID:	(WOS)000522703800001 (Scopus)85083217977
Első szerző:	Kiss Tamás (vegyész)
Cím:	Single-cell RNA sequencing identifies senescent cerebromicrovascular endothelial cells in the aged mouse brain / Kiss Tamas, Nyúl-Tóth Ádám, Balasubramanian Priya, Tarantini Stefano, Ahire Chetan, DelFavero Jordan, Yabluchanskiy Andriy, Csipo Tamas, Farkas Eszter, Wiley Graham, Garman Lori, Csiszar Anna, Ungvari Zoltan
Dátum:	2020
ISSN:	2509-2715 2509-2723
Megjegyzések:	Age-related phenotypic changes of cerebromicrovascular endothelial cells lead to dysregulation of cerebral blood flow and blood-brain barrier disruption, promoting the pathogenesis of vascular cognitive impairment (VCI). In recent years, endothelial cell senescence has emerged as a potential mechanism contributing to microvascular pathologies opening the avenue to the therapeutic exploitation of senolytic drugs in preclinical studies. However, difficulties with the detection of senescent endothelial cells in wild type mouse models of aging hinder the assessment of the efficiency of senolytic treatments. To detect senescent endothelial cells in the aging mouse brain, we analyzed 4233 cells in fractions enriched for cerebromicrovascular endothelial cells and other cells associated with the neurovascular unit obtained from young (3-month-old) and aged (28-month-old) C57BL/6 mice. We define 13 transcriptomic cell types by deep, single-cell RNA sequencing. We match transcriptomic signatures of cellular senescence to endothelial cells identified on the basis of their gene expression profile. Our study demonstrates that with advanced aging, there is an increased ratio of senescent endothelial cells (~ 10%) in the mouse cerebral microcirculation. We propose that our single-cell RNA sequencing-based method can be adapted to study the effect of aging on senescence in various brain cell types as well as to evaluate the efficiency of various senolytic regimens in multiple tissues.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Aging Blood-brain barrier Geroscience Senescence Vascular cognitive impairment
Megjelenés:	GeroScience. - 42 : 2 (2020), p. 429-444. -
További szerzők:	Nyúl-Tóth Ádám Balasubramanian, Priya Tarantini, Stefano Ahire, Chetan DelFavero, Jordan Yabluchanskiy, Andriy Csípő Tamás (1990-) Farkas Eszter Wiley, Graham Garman, Lori Csiszár Anna Ungvári Zoltán
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM099925
035-os BibID:	(WOS)000516267700001 (Scopus)85079528822
Első szerző:	Kiss Tamás (vegyész)
Cím:	Nicotinamide mononucleotide (NMN) supplementation promotes neurovascular rejuvenation in aged mice : transcriptional footprint of SIRT1 activation, mitochondrial protection, anti-inflammatory, and anti-apoptotic effects / Kiss Tamas, Nyúl-Tóth Ádám, Balasubramanian Priya, Tarantini Stefano, Ahire Chetan, Yabluchanskiy Andriy, Csipo Tamas, Farkas Eszter, Wren Jonathan D., Garman Lori, Csiszar Anna, Ungvari Zoltan
Dátum:	2020
ISSN:	2509-2715 2509-2723
Megjegyzések:	Aging-induced structural and functional alterations of the neurovascular unit lead to impairment of neurovascular coupling responses, dysregulation of cerebral blood flow, and increased neuroinflammation, all of which contribute importantly to the pathogenesis of age-related vascular cognitive impairment (VCI). There is increasing evidence showing that a decrease in NAD+ availability with age plays a critical role in age-related neurovascular and cerebromicrovascular dysfunction. Our recent studies demonstrate that restoring cellular NAD+ levels in aged mice rescues neurovascular function, increases cerebral blood flow, and improves performance on cognitive tasks. To determine the effects of restoring cellular NAD+ levels on neurovascular gene expression profiles, 24-month-old C57BL/6 mice were treated with nicotinamide mononucleotide (NMN), a key NAD+ intermediate, for 2 weeks. Transcriptome analysis of preparations enriched for cells of the neurovascular unit was performed by RNA-seq. Neurovascular gene expression signatures in NMN-treated aged mice were compared with those in untreated young and aged control mice. We identified 590 genes differentially expressed in the aged neurovascular unit, 204 of which are restored toward youthful expression levels by NMN treatment. The transcriptional footprint of NMN treatment indicates that increased NAD+ levels promote SIRT1 activation in the neurovascular unit, as demonstrated by analysis of upstream regulators of differentially expressed genes as well as analysis of the expression of known SIRT1-dependent genes. Pathway analysis predicts that neurovascular protective effects of NMN are mediated by the induction of genes involved in mitochondrial rejuvenation, anti-inflammatory, and anti-apoptotic pathways. In conclusion, the recently demonstrated protective effects of NMN treatment on neurovascular function can be attributed to multifaceted sirtuin-mediated anti-aging changes in the neurovascular transcriptome. Our present findings taken together with the results of recent studies using mitochondria-targeted interventions suggest that mitochondrial rejuvenation is a critical mechanism to restore neurovascular health and improve cerebral blood flow in aging.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Aging Geroscience Mitochondria dysfunction Transcriptomics Vascular cognitive impairment
Megjelenés:	GeroScience. - 42 : 2 (2020), p. 527-546. -
További szerzők:	Nyúl-Tóth Ádám Balasubramanian, Priya Tarantini, Stefano Ahire, Chetan Yabluchanskiy, Andriy Csípő Tamás (1990-) Farkas Eszter Wren, Jonathan D. Garman, Lori Csiszár Anna Ungvári Zoltán
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon: