Impaired Regulation of Muscle size with Aging

人们对控制肌肉大小的机制知之甚少，也不清楚幼年动物和老年动物的肌肉是否也涉及同样的机制。因此，这项研究的目标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。以下假设将被解决：衰老与在萎缩诱发事件面前保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这一假设。具体目的1将研究幼年、成年和老年大鼠肌肉对萎缩诱导事件(后肢悬吊)、防止萎缩干预(后肢悬吊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)的反应的差异。将确定老年大鼠的肌肉对萎缩诱导事件的反应是否与年轻大鼠的肌肉相同，以及老年大鼠的肌肉是否能像年轻大鼠的肌肉一样恢复大小。在特定的目标中，正在研究两种已知的影响幼年动物肌肉大小的不同机制，以确定这些机制是否也在年长的肌肉中以同样的程度参与。卫星细胞在幼年、成年和老年大鼠的肌肉中发挥的作用和细胞凋亡的参与将在上述实验范式中进行研究。在特定的目标2中，我们将确定肌肉中基因表达的差异，经历不同的实验操作，并比较年轻肌肉、成年肌肉和老年肌肉中基因表达的变化。我们将研究一些已知在骨骼肌萎缩和肥大中起作用的基因，但我们也将使用cDNA微阵列技术来扫描大量尚不清楚的基因，这些基因尚未参与肌肉大小的调节。这些研究的结果将表明，老年动物的肌肉是否恢复或保持与年轻动物相同的肌肉质量，以及与年轻动物相比，老年动物肌肉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控途径和分子。

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.