Mechanisms of Dysfunction in the Aging Vasculature and Role in Age-Related Disease.
Mechanisms of Dysfunction in the Aging Vasculature and Role in Age-Related Disease.
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DOI：
10.1161/circresaha.118.312563
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发表时间：
2018-09-14
影响因子：
20.1
通讯作者：
Lesniewski LA
中科院分区：
文献类型：
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作者：
Donato AJ;Machin DR;Lesniewski LA
年龄增长会导致心血管疾病(CVD)，心血管疾病是美国和许多发达国家的主要死亡原因。与年龄相关的两种主要动脉表型，大弹性动脉硬化和内皮功能障碍，是未来CVD诊断的独立预测因素，可能是老年人CVD发生的原因。不仅限于传统的心血管疾病，这些与年龄相关的血管变化也会导致其他与年龄相关的疾病，这些疾病会影响哺乳动物的健康寿命和潜在寿命。该综述通过炎症和氧化应激在组织水平和细胞水平上通过Klotho和能量感应通路(AMPK、sirtuins、mTOR)来探讨影响与年龄相关的大弹性动脉硬化和内皮功能障碍的机制。我们还讨论了长期热量限制，一种健康和延长寿命的干预措施，如何通过防止这些机制中的有害变化来预防许多与年龄相关的血管表型。最后，我们讨论了新出现的血管衰老的新机制，包括血管细胞内的衰老和基因组不稳定。随着老年人口的稳步增长，阐明随年龄增长的血管功能障碍的细胞和分子机制对于更好地指导适当和有节制的策略至关重要，这些策略利用药理学和生活方式干预来预防这一人群中的心血管疾病风险。
Advancing age promotes cardiovascular disease (CVD), the leading cause of death in the United States and many developed nations. Two major age-related arterial phenotypes, large elastic artery stiffening and endothelial dysfunction, are independent predictors of future CVD diagnosis and likely are responsible for the development of CVD in older adults. Not limited to traditional CVD, these age-related changes in the vasculature also contribute to other age-related diseases that influence mammalian healthspan and potential lifespan. This review explores mechanisms that influence age-related large elastic artery stiffening and endothelial dysfunction at the tissue level via inflammation and oxidative stress, and at the cellular level via Klotho and energy sensing pathways (AMPK, Sirtuins, mTOR). We also discuss how long-term calorie restriction, a healthspan and lifespan extending intervention, can prevent many of these age-related vascular phenotypes through the prevention of deleterious alterations in these mechanisms. Lastly, we discuss emerging novel mechanisms of vascular aging, including senescence and genomic instability within cells of the vasculature. As the population of older adults steadily expands, elucidating the cellular and molecular mechanisms of vascular dysfunction with age is critical to better direct appropriate and measured strategies that utilize pharmacological and lifestyle interventions to prevent against CVD risk within this population.