期刊
SCIENCE ADVANCES
卷 8, 期 25, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abm6756
关键词
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资金
- Technion Research & Development Foundation
- Technion-Israel Institute of Technology
- University of Miami
- Frost Endowed Scholarship
- Monasterium Laboratory, Munster
Transplanting aged human skin onto young SCID/beige mice can rejuvenate the skin and improve aging-related biomarkers. The rejuvenation cascade is initiated by murine VEGF-A, which up-regulates VEGF-A expression/secretion within aged human skin. VEGF-A is identified as the first pharmacologically pliable master pathway for human organ rejuvenation in vivo.
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 beta-galactosidase, p16(ink4a), SIRT1, PGC1 alpha, collagen 17A, and MMP1. Angiogenesis-and hypoxia-related pathways, namely, vascular endothelial growth factor A (VEGF-A) and HIFI A, 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.
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