CARDIAC ABNORMALITIES & CALORIC RESTRICTION

描述：（改编自研究者摘要）研究者是 建议研究早期和成人开始的热量限制的影响， (CR)与年龄相关的心脏功能、结构和 线粒体异常CR是一种稳健且可重复的干预措施 能够在很宽的范围内增加平均寿命和最大寿命， 物种减少热量摄入发挥这种作用的机制 影响是未知的，然而，有越来越多的证据表明，热量 限制功能通过减少氧化应激和随后的氧化 对细胞生物分子的损害。 线粒体遗传和酶异常与许多 遗传性线粒体疾病，越来越多的证据表明， 线粒体异常的生理相关积累， 退化性老化过程。这些研究人员和其他人已经证明了线粒体DNA 缺失可以在细胞中积累到高水平， 蓄积是线粒体电子传递系统异常。他们的 局灶性积聚和镶嵌分布决定了组织学方法 提出了 F344BNF 1菌株的使用是拟议研究的一个重要方面。 这种大鼠品系对许多与年龄有关的病理学不太敏感 通常在大鼠模型中发现（例如，肾病），可能存在混淆 心脏变化的机制不同年龄动物的大鼠心脏将被 第一次以生理学研究为特征。然后将心脏组织 采用LV功能的可量化测量进行组织学评估， 组织结构的变化，心肌细胞的丰度表现出 线粒体异常和经历细胞凋亡的心肌细胞数量 死亡这些生理学和组织学研究也将在 大鼠经受早期和与人类衰老最密切相关的成年发病CR。

DESCRIPTION: (adapted from Investigator's abstract) The investigators are proposing to study the effects of early- and adult-onset caloric restriction (CR) on age-associated changes in cardiac function, structure, and mitochondrial abnormalities. CR is a robust and reproducible intervention capable of increasing both mean and maximum life span in a wide range of species. The mechanism by which a reduction in caloric intake exerts this effect is not known, however, there is increasing evidence that caloric restriction functions by decreasing oxidative stress and subsequent oxidative damage to cellular biomolecules. Mitochondrial genetic and enzymatic abnormalities have been linked to many inherited mitochondrial disorders, and there is increasing evidence for physiologically relevant accumulations of mitochondrial abnormalities in degenerative aging processes. These investigators and others have shown mtDNA deletions can accumulate to high levels in cells and that associated with this accumulation are mitochondrial electron transport system abnormalities. Their focal accumulation and mosaic distribution dictates the histologic approaches proposed. The use of the F344BNF1 strain is an important aspect of the proposed studies. This rat strain is less susceptible to many of the age-related pathologies commonly found in rat models (e.g., nephropathy) that can present confounding mechanisms for cardiac changes Rat hearts from animals of diverse ages will be first characterized by physiologic studies. The cardiac tissue will then be histologically assessed employing the quantifiable measures of LV function, changes in histological structure, abundance of cardiomyocytes exhibiting mitochondrial abnormalities and numbers of cardiomyocytes undergoing cell death. These physiological and histological studies will also be conducted on rats subjected to early- and, most germane to human aging, adult-onset CR.