Dataset Information

Human organ rejuvenation by VEGF-A: Lessons from the skin.

ABSTRACT: Transplanting aged human skin onto young SCID/beige mice morphologically rejuvenates the xenotransplants. This is accompanied by angiogenesis, epidermal repigmentation, and substantial improvements in key aging-associated biomarkers, including ß-galactosidase, p16^ink4a, SIRT1, PGC1α, collagen 17A, and MMP1. Angiogenesis- and hypoxia-related pathways, namely, vascular endothelial growth factor A (VEGF-A) and HIF1A, are most up-regulated in rejuvenated human skin. This rejuvenation cascade, which can be prevented by VEGF-A-neutralizing antibodies, appears to be initiated by murine VEGF-A, which then up-regulates VEGF-A expression/secretion within aged human skin. While intradermally injected VEGF-loaded nanoparticles suffice to induce a molecular rejuvenation signature in aged human skin on old mice, VEGF-A treatment improves key aging parameters also in isolated, organ-cultured aged human skin, i.e., in the absence of functional skin vasculature, neural, or murine host inputs. This identifies VEGF-A as the first pharmacologically pliable master pathway for human organ rejuvenation in vivo and demonstrates the potential of our humanized mouse model for clinically relevant aging research.

SUBMITTER: Keren A

PROVIDER: S-EPMC9232104 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Human organ rejuvenation by VEGF-A: Lessons from the skin.

Keren Aviad A Bertolini Marta M Keren Yaniv Y Ullmann Yehuda Y Paus Ralf R Gilhar Amos A

Science advances 20220624 25

Transplanting aged human skin onto young SCID/beige mice morphologically rejuvenates the xenotransplants. This is accompanied by angiogenesis, epidermal repigmentation, and substantial improvements in key aging-associated biomarkers, including ß-galactosidase, p16<sup>ink4a</sup>, SIRT1, PGC1α, collagen 17A, and MMP1. Angiogenesis- and hypoxia-related pathways, namely, vascular endothelial growth factor A (VEGF-A) and HIF1A, are most up-regulated in rejuvenated human skin. This rejuvenation casc ...[more]

PMID: 35749494

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Dataset Information

Human organ rejuvenation by VEGF-A: Lessons from the skin.

Publications

Human organ rejuvenation by VEGF-A: Lessons from the skin.

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