ROLE OF ION CHANNELS IN SARCOPENIA

描述：（逐字从应用程序）最严重的问题之一 老年人容易跌倒是行动能力受损的主要原因。福尔斯占 几乎90%的老年人骨折。中的限制 进行日常生活活动和福尔斯坠落无疑与 姿势肌肉的变化。姿势肌与稳定有关 站立时身体的一部分在另一部分上。这种肌肉亚群表现出 慢肌纤维含量高。在许多成年哺乳动物的比目鱼肌中 这种纤维的比例接近100%（超过80 人的百分比）。虽然姿势的关键作用，机械 单一完整慢纤维的性质和分子机制 还没有研究老年人或衰老的动物模型中的收缩。 不幸的是，关于快缩纤维的年龄相关变化的信息 不能外推到慢纤维， 两种纤维亚型之间的结构和生化差异。 这一提议的假设是， 1型纤维中DHPR受体基因的表达导致 骨骼肌力量随年龄增长而变化。DHPR的数量较少， 未连接且不能被肌膜激活的RyR 1数量 去极化，导致肌浆网实质性下降 老化慢缩肌肉的钙内流与收缩力。这一假设 将使用以下具体目标进行评估：（1）确定是否 单个骨骼肌纤维收缩力的下降与 单次慢收缩心肌细胞内钙浓度峰值的改变 (type 1）年轻（7个月）、中年（14）和老年（28）的肌纤维 c57 bl/6小鼠(2)确定1型糖尿病患者的年龄相关性损害是否 肌浆网Ca 2+减少导致纤维收缩 release. (3)为了确定是否与年龄相关的功能下降， 监测的DHPR与测量的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，和（4）To 定义是否在慢肌中DHPR和/或RyR 1表达的改变， 衰老小鼠是由于DHPR核转录活性下降所致 α 1、α 2、β、γ和δ亚基和/或RyR 1 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.