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Aging, physical activity, and cardiac apoptosis

衰老、体力活动和心脏细胞凋亡

基本信息

批准号：
6665999
负责人：
MICHAEL J TURNER
金额：
$ 19.88万
依托单位：
UNIVERSITY OF NORTH CAROLINA CHARLOTTE
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-01 至 2007-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): One's physical activity level is known to decrease with age. This decrement in activity has been shown to be associated with age-associated health concerns, i.e., obesity, diabetes, and cardiovascular disease. Recent research in our laboratory has shown a genetic influence in the age-associated change in physical activity patterns. Therefore, this research study will study the genetic influence on physical activity level during the aging process. In addition, we will investigate the relationship of physical activity and cardiac cell death in aging mice. This project will be the first to determine the influence of genetics on the age-related decline in physical activity level, as well as the relationship between the age-related changes in physical activity and cardiac apoptosis in inbred mice. One hundred ninety mice (male and female) will be studied. Initially we will breed our progenitor strains (DBA/2J x SWR/J) to generate our F1 (20 mice). After a brief period to phenotype our F1 population, we will generate backcross mice (40 mice) to allow for segregation analysis. Lastly, F2 (130 mice) will be produced for the performance of segregation and linkage analysis. Our pilot research has found these inbred strains to possess differing age-related changes in physical activity patterns. All mice will be housed separately (at age 6 weeks) in a cage with a suspended running wheel to measure the daily distance traveled and duration of activity. At specific time points (10 mice at ages 6 weeks, 26 weeks, and 39 weeks), F2 mice will be randomly selected to be sacrificed for the genetic analysis and measurement of cardiac apoptosis. Additionally, at one year of age, all F1, backcross, and remaining F2 mice will be sacrificed for genetic analysis and measurement of cardiac apoptosis. The spleen, lungs, and kidneys will be removed for the separation of RNA for linkage analysis. The hearts will be removed with portions of the left and right ventricles fixed for later determination of apoptosis activity by TUNEL assay and DNA laddering. We hypothesize: 1) a polygenic influence on the age-related decrease in physical activity and 2) a significant relationship between the changes in age-associated physical activity level and amount of cardiac apoptosis. The information gathered from these studies will provide the foundation for future studies whose purpose will be to further delineate the location and specific genetic control of physical activity with aging.

描述（由申请人提供）：一个人的体力活动水平是众所周知的，随着年龄的增长而下降。这种活动的减少已被证明与年龄相关的健康问题有关，即，肥胖、糖尿病和心血管疾病。我们实验室最近的研究表明，与年龄相关的身体活动模式变化存在遗传影响。因此，本研究将研究在衰老过程中遗传对体力活动水平的影响。此外，我们还将研究体力活动与衰老小鼠心脏细胞死亡的关系。该项目将首次确定遗传对与年龄相关的体力活动水平下降的影响，以及与年龄相关的体力活动变化与近交系小鼠心脏细胞凋亡之间的关系。将研究190只小鼠（雄性和雌性）。最初，我们将繁殖我们的祖先品系（DBA/2 J x SWR/J）以产生我们的F1（20只小鼠）。在对我们的F1群体进行短暂的表型化后，我们将产生回交小鼠（40只小鼠）以进行分离分析。最后，将生产F2（130只小鼠）用于分离和连锁分析。我们的初步研究发现，这些近交系在身体活动模式上具有不同的年龄相关变化。将所有小鼠单独饲养（6周龄）在带有悬挂式转轮的笼中，以测量每日行进距离和活动持续时间。在特定时间点（6周龄、26周龄和39周龄的10只小鼠），将随机选择F2小鼠处死，用于遗传分析和心脏细胞凋亡的测量。此外，在1岁时，将处死所有F1、回交和剩余F2小鼠，用于遗传分析和心脏细胞凋亡的测量。取出脾、肺和肾，分离RNA进行连锁分析。取出心脏，固定部分左心室和右心室，用于随后通过TUNEL测定和DNA梯状法测定细胞凋亡活性。我们假设：1）多基因影响与年龄相关的体力活动减少; 2）与年龄相关的体力活动水平的变化与心脏细胞凋亡量之间存在显著关系。从这些研究中收集到的信息将为未来的研究提供基础，其目的是进一步描述身体活动与衰老的位置和特定的遗传控制。