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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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