ROLE OF ION CHANNELS IN SARCOPENIA

描述：(来自应用程序的逐字)最严重的问题之一 行动不便的主要原因是老年人跌倒的倾向。瀑布占了 几乎90%的老年人骨折。中的限制 表演日常生活活动和跌倒无疑与 姿势肌肉的变化。姿势肌肉与稳定有关。 身体的一部分站在另一个身体上。这一肌肉亚群表现出 慢肌纤维含量高。在许多成年哺乳动物的比目鱼肌中 该类型纤维的比例接近100%(超过80% 人类的百分比)。尽管姿势的关键作用，机械的 单根完整慢纤维的性能及其分子机制 老年人的收缩或衰老的动物模型还没有被探索过。 不幸的是，关于快速抽动纤维的年龄相关变化的信息 不能外推到慢纤维由于大量的生理因素， 两种纤维亚型之间的结构和生化差异。 这一提议的假设是二氢吡啶的减少 受体(DHPR)基因在1型纤维中的表达导致 骨骼肌力随年龄增长。较低的DHPR数量会导致显著的 未连接且无法被肌膜激活的RyR1的数量 去极化，导致石棺网状结构的显著下降 衰老慢抽动肌的钙离子内流和收缩力。这一假设 将使用以下具体目标进行评估：(1)确定是否 单一骨骼肌纤维收缩能力的下降与 单次慢收缩时细胞内最大钙离子浓度的变化 (类型1)年轻(7个月)、中年(14个月)和老年(28个月)的肌肉纤维 C57BL/6小鼠。(2)确定1型的年龄相关性损害是否 肌浆网钙离子减少导致纤维收缩 放手。(3)确定与年龄相关的功能衰退是否 监测的DHPR与所测量的DHPR基因表达的减少有关 在同一类型-1单个肌纤维或整个比目鱼肌中，以及(4)到 确定DHPR和/或RyR1在慢肌中的表达变化是否 衰老小鼠是DHPR核转录活性下降所致 Alpha1、Alpha2、Beta、Gamma和Delta亚基和/或RyR1 DNA。

DESCRIPTION: (Verbatim from the application) One of the most serious problems of mobility impairment is the tendency of old adults to fall. Falls account for almost 90 percent of all fractures in the elderly. The limitations in performing activities of daily living and falls are undoubtedly associated with alterations on postural muscles. Postural muscles are concerned with steadying a segment of the body on another in standing. This muscle subgroup exhibits a high content of slow muscle fibers. In the soleus muscle of many adult mammals the proportion of this type of fiber approaches 100 percent (more than 80 percent in humans). Although the crucial role in posture, the mechanical properties and the molecular mechanisms involved in single intact slow fibers contraction in the elderly or animal models of aging have not been explored. Unfortunately the information about age-related changes in fast-twitch fibers cannot be extrapolated to slow fibers due to substantial physiological, structural and biochemical differences between the two fiber subtypes. The hypothesis of this proposal is that the decrease in dihydropyridine receptor (DHPR) gene expression in type-1 fibers results in a decline in skeletal muscle force with aging. A lower number of DHPR renders a significant number of RyR1 unlinked and unable to be activated by sarcolemmal depolarization, leading to a substantial decline in sarcopasmic reticulum Ca2+influx and contractile force in aging slow-twitch muscles. This hypothesis will be assessed using the following specific aims: (1) To determine whether the decline in single skeletal muscle fiber contractility is associated with alterations in peak intracellular calcium concentration in single slow-twitch (type 1) muscle fibers from young (7months), middle-age (14), and old (28) C57BL/6 mice. (2) To establish whether the age-related impairment in type-1 fiber contractility results from a reduction in sarcoplasmic reticulum Ca2+ release. (3) To determine whether the age-related decline in functionally monitored DHPR is associated with a decrease in DHPR gene expression measured in the same type-1 single muscle fiber or whole soleus muscle, and (4) To define whether alterations in DHPR and/or RyR1 expression in slow muscle from aging mice results from a decline in nuclear transcriptional activity of DHPR alpha1, alpha2, beta, gamma and delta subunits and/orRyR1 DNA.