Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging.,Cell

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Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging.
Cell ( IF 45.5 ) Pub Date : 2018-Mar-22 , DOI: 10.1016/j.cell.2018.02.008
Abhirup Das ₁ , George X Huang ₂ , Michael S Bonkowski ₃ , Alban Longchamp ₄ , Catherine Li ₅ , Michael B Schultz ₃ , Lynn-Jee Kim ₅ , Brenna Osborne ₆ , Sanket Joshi ₆ , Yuancheng Lu ₃ , Jose Humberto Treviño-Villarreal ₄ , Myung-Jin Kang ₅ , Tzong-Tyng Hung ₇ , Brendan Lee ₇ , Eric O Williams ₈ , Masaki Igarashi ₈ , James R Mitchell ₄ , Lindsay E Wu ₅ , Nigel Turner ₆ , Zolt Arany ₉ , Leonard Guarente ₈ , David A Sinclair ₁₀

Affiliation

Paul F. Glenn Center for the Biological Mechanisms of Aging, Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Laboratory for Ageing Research, Department of Pharmacology, School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia; Paul F. Glenn Center for Science of Aging Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Paul F. Glenn Center for the Biological Mechanisms of Aging, Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, Bldg. 421, Philadelphia, PA 19104, USA.
Paul F. Glenn Center for the Biological Mechanisms of Aging, Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Laboratory for Ageing Research, Department of Pharmacology, School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia.
Mitochondrial Bioenergetics Laboratory, Department of Pharmacology, School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia.
Biological Resources Imaging Laboratory, Mark Wainwright Analytical Centre, The University of New South Wales, Sydney, NSW 2052, Australia.
Paul F. Glenn Center for Science of Aging Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, Bldg. 421, Philadelphia, PA 19104, USA.
Paul F. Glenn Center for the Biological Mechanisms of Aging, Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Laboratory for Ageing Research, Department of Pharmacology, School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia.

A decline in capillary density and blood flow with age is a major cause of mortality and morbidity. Understanding why this occurs is key to future gains in human health. NAD precursors reverse aspects of aging, in part, by activating sirtuin deacylases (SIRT1-SIRT7) that mediate the benefits of exercise and dietary restriction (DR). We show that SIRT1 in endothelial cells is a key mediator of pro-angiogenic signals secreted from myocytes. Treatment of mice with the NAD⁺ booster nicotinamide mononucleotide (NMN) improves blood flow and increases endurance in elderly mice by promoting SIRT1-dependent increases in capillary density, an effect augmented by exercise or increasing the levels of hydrogen sulfide (H₂S), a DR mimetic and regulator of endothelial NAD⁺ levels. These findings have implications for improving blood flow to organs and tissues, increasing human performance, and reestablishing a virtuous cycle of mobility in the elderly.

中文翻译：

内皮NAD + -H2S信号网络的损害是血管衰老的可逆原因。

随着年龄的增长，毛细血管密度和血流量下降是导致死亡和发病的主要原因。理解为什么会发生这种情况对于人类未来的健康发展至关重要。NAD前体可通过激活调节运动和饮食限制（DR）益处的瑟土因脱酰基酶（SIRT1-SIRT7）来部分逆转衰老。我们显示内皮细胞中的SIRT1是从肌细胞分泌的促血管生成信号的关键介体。用NAD ⁺增强型烟酰胺单核苷酸（NMN）治疗小鼠可促进SIRT1依赖性毛细血管密度的增加，从而改善老年小鼠的血流量并增强其耐力，这种作用可通过运动或增加硫化氢（H ₂ S）的水平来增强， DR模拟物和内皮NAD调节剂⁺水平。这些发现对于改善流向器官和组织的血液，提高人类的机能以及在老年人中建立良好的活动性循环具有重要意义。

更新日期：2018-03-22

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