CARDIAC ABNORMALITIES & CALORIC RESTRICTION

描述：(改编自调查人员摘要)调查人员是 建议研究早期和成人卡路里限制的影响 (Cr)与年龄相关的心脏功能、结构和 线粒体异常。CR是一种强大且可重复性的干预手段 能够在很大范围内提高平均寿命和最高寿命 物种。卡路里摄入量的减少产生这种影响的机制 影响尚不清楚，然而，越来越多的证据表明，卡路里 通过减少氧化应激和随后的氧化来限制功能 对细胞生物分子的损伤。 线粒体遗传和酶的异常与许多 遗传性线粒体疾病，而且有越来越多的证据表明 与生理相关的线粒体异常堆积 退化的衰老过程。这些调查人员和其他人已经证明了线粒体DNA 删除可能会累积到单元格中的高水平，以及与此相关的删除 堆积是线粒体电子传递系统的异常。他们的 局灶性堆积和镶嵌分布决定了组织学方法 建议。 F344BNF1菌株的使用是拟议研究的一个重要方面。 这种品系的大鼠对许多与年龄相关的疾病不太敏感 常见于大鼠模型(如肾病)，可呈现混乱性 不同年龄动物的心脏改变的机制将是 首先以生理学研究为特征的。然后心脏组织将被 采用可量化的左心功能测量方法进行组织学评估， 心肌细胞的组织结构、丰度的变化 细胞周期中心肌细胞线粒体的异常和数量 死亡。这些生理和组织学研究也将在 早期--而且大多数与人类衰老密切相关的--成年发病的CR的大鼠。

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.