血管老化的机制。
Mechanisms of Vascular Aging.
机构信息
From the Vascular Cognitive Impairment Laboratory, Reynolds Oklahoma Center on Aging (Z.U., S.T., A.C.), University of Oklahoma Health Sciences Center, Oklahoma City.
Department of Geriatric Medicine, Translational Geroscience Laboratory (Z.U., S.T., A.C.), University of Oklahoma Health Sciences Center, Oklahoma City.
出版信息
Circ Res. 2018 Sep 14;123(7):849-867. doi: 10.1161/CIRCRESAHA.118.311378.
Aging of the vasculature plays a central role in morbidity and mortality of older people. To develop novel treatments for amelioration of unsuccessful vascular aging and prevention of age-related vascular pathologies, it is essential to understand the cellular and functional changes that occur in the vasculature during aging. In this review, the pathophysiological roles of fundamental cellular and molecular mechanisms of aging, including oxidative stress, mitochondrial dysfunction, impaired resistance to molecular stressors, chronic low-grade inflammation, genomic instability, cellular senescence, epigenetic alterations, loss of protein homeostasis, deregulated nutrient sensing, and stem cell dysfunction in the vascular system are considered in terms of their contribution to the pathogenesis of both microvascular and macrovascular diseases associated with old age. The importance of progeronic and antigeronic circulating factors in relation to development of vascular aging phenotypes are discussed. Finally, future directions and opportunities to develop novel interventions to prevent/delay age-related vascular pathologies by targeting fundamental cellular and molecular aging processes are presented.
血管老化在老年人的发病率和死亡率中起着核心作用。为了开发改善血管老化失败和预防与年龄相关的血管病变的新疗法，了解血管在衰老过程中发生的细胞和功能变化至关重要。在这篇综述中，考虑了衰老的基本细胞和分子机制的病理生理作用，包括氧化应激、线粒体功能障碍、对分子应激源的抵抗力降低、慢性低度炎症、基因组不稳定性、细胞衰老、表观遗传改变、蛋白质平衡丧失、营养感应失调和干细胞功能障碍，这些机制在与衰老相关的微血管和大血管疾病的发病机制中的作用。讨论了与血管老化表型发展相关的促衰老和抗衰老循环因子的重要性。最后，提出了通过针对基本的细胞和分子衰老过程来开发预防/延缓与年龄相关的血管病变的新干预措施的未来方向和机会。
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