Impaired Regulation of Muscle size with Aging

随着年龄的增长，肌肉大小的调节能力受损

基本信息

批准号：
6439793
负责人：
Esther E Dupont-Versteegden
金额：
$ 7.3万
依托单位：
UNIV OF ARKANSAS FOR MED SCIS
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-02-01 至 2004-01-31
项目状态：
已结题

项目摘要

Mechanisms controlling muscle size are poorly understood and it is unknown whether the same mechanisms are involved in muscles from young and old animals. Therefore, the goal of this study is to gain insight into mechanisms controlling muscle size and to determine whether these mechanisms are similar between young and old. The following hypothesis will be addressed: aging is associated with an impaired ability to maintain or restore muscles size in the face of an atrophy-inducing event. Three specific aims will be executed to address the hypothesis. In Specific Aim 1 the differences between young, adult and old rat muscles will be investigated in response to an atrophy-inducing event (hind limb suspension), to an atrophy preventing intervention (intermittent reloading during hind limb suspension) and a muscle mass restoring intervention (reloading after hind limb suspension)> It will be determine whether muscles from older rats react to the atrophy inducing events the same as muscles from young rats and whether the muscles from old rats can be restored in size as muscles from young rats are. In Specific Aim 2 different mechanisms known to influence muscle size in young animals are being investigated to determine whether these mechanisms are also involved to the same extent in older muscle. The role that satellite cells play and the involvement of apoptosis will be investigated in muscles from young, adult and old rats undergoing the above mentioned experimental paradigms. In Specific Aim 2 we will determine differences in gene expression in the muscles, undergoing the different experimental manipulations and compare changes in gene expression between young, adult and old muscles. We will look at a number of genes known to play a role in skeletal muscle atrophy and hypertrophy, but we will also use cDNA micro array technology to scan large numbers of genes that are not known yet to be involved in the regulation of muscle size. Results from these studies will indicate whether muscles from older animals restore or maintain muscle mass to the same extent as young animals and if underlying mechanisms are different in old compared to young muscles. Also, potential regulatory pathways and molecules involved in control of muscle size will be determined.

人们对控制肌肉大小的机制知之甚少，并且尚不清楚年轻和年老动物的肌肉是否涉及相同的机制。因此，本研究的目的是深入了解控制肌肉大小的机制，并确定这些机制在年轻人和老年人之间是否相似。将解决以下假设：衰老与面对萎缩诱发事件时维持或恢复肌肉大小的能力受损有关。将执行三个具体目标来解决该假设。在具体目标 1 中，将研究年轻、成年和老年大鼠肌肉之间的差异，以响应萎缩诱发事件（后肢悬挂）、预防萎缩干预（后肢悬挂期间间歇性重新加载）和肌肉质量恢复干预(后肢悬吊后重新加载)>将确定老年大鼠的肌肉是否与年轻大鼠的肌肉一样对萎缩诱导事件做出反应，以及老年大鼠的肌肉是否可以恢复与年轻大鼠的肌肉一样的大小。在Specific Aim 2中，正在研究已知影响年轻动物肌肉大小的不同机制，以确定这些机制是否也以相同程度涉及老年肌肉。将在经历上述实验范式的年轻、成年和老年大鼠的肌肉中研究卫星细胞所发挥的作用和细胞凋亡的参与。在具体目标 2 中，我们将通过不同的实验操作来确定肌肉中基因表达的差异，并比较年轻、成人和老年肌肉之间基因表达的变化。我们将研究一些已知在骨骼肌萎缩和肥大中发挥作用的基因，但我们还将使用 cDNA 微阵列技术扫描大量尚不知道参与肌肉大小调节的基因。这些研究的结果将表明年老动物的肌肉是否恢复或维持与年轻动物相同的肌肉质量，以及年老动物与年轻动物的潜在机制是否不同。此外，还将确定参与控制肌肉大小的潜在调节途径和分子。