Biomarkers of Cardiovascular Aging

心血管衰老的生物标志物

• 批准号: 10913154
• 负责人: Edward Lakatta
• 金额: $ 2.02万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10913154
• 关键词: Adrenergic Agents; Age; Age Months; Aging; Alzheimer' s Disease; Animal Model; Animals; Ants; Biological Markers; Blood Vessels; Brain; Cardiac; Cardiovascular system; Cessation of life; Clinical Research; Dementia; Diabetes Mellitus; Echocardiography; Elderly; Electrocardiogram; Endocrine system; Future; Gene Expression Profile; Goals; Healthcare Systems; Heart Rate; Heart failure; Human; Individual; Intervention; Investigation; Longevity; Malignant Neoplasms; Medical; Mus; Physiological; Population; Process; Research Project Grants; Societies; Stroke; age effect; cohort; healthspan; heart rate variability; neural; pre-clinical; programs; social

The broad objective of this program is to perform preclinical experimentation on animal models of aging to elucidate the possible biomarkers that strongly associated with health span and lifespan of mouse. For that purpose, we used echocardiography to observed cardiac and vascular physiological parameters non-invasively in a cohort of 58 mice from 3 months of age to their natural deaths of everyone in a 3-month interval. We also recorded ECG with and without autonomic blockade to elucidate the changes with intrinsic heart rate by age. Preliminary results indicated that regardless of absolute lifespan of mice, most of the cardiac and vascular physiological parameters we observed showed clear longitudinal trajectories when adjusted to percent of lifespan that calculated retrospectively for each individual subject. From these trajectories, lifespan of an individual subject may be predicted. On the other hand, trajectories of HR, Intrinsic HR and HRV showed clear age-associated changes in brain adrenergic drive, increases in sympathetic drive while reduction in parasympathetic drive, by age in mice. The relationship between gene expression profile of SAN and changes in intrinsic HR and HRV are currently under investigation.

该程序的广泛目的是对衰老动物模型进行临床前实验，以阐明与健康跨度和寿命密切相关的生物标志物。 为此，我们使用超声心动图来观察到从3个月大的58只小鼠组成的58只小鼠，到每个人的自然死亡，以3个月的间隔观察到心脏和血管生理参数。我们还记录了具有和没有自主性阻滞的ECG，以阐明按年龄的内在心率的变化。初步结果表明，无论小鼠的绝对寿命如何，我们观察到的大多数心脏和血管生理参数都显示出明确的纵向轨迹，当调整到为每个受试者回顾性计算的寿命百分比时。从这些轨迹中，可以预测单个受试者的寿命。另一方面，人力资源，内在的HR和HRV的轨迹显示出与小鼠的年龄减少，同时减少副交感神经驱动器，同时驱动的同时驱动，同时驱动型的变化明显。目前正在研究SAN基因表达谱与内在HR和HRV的变化之间的关系。