EXCITATION CONTRACTION COUPLING IN AGING MUSCLE

本研究的长期目标是阐明机制 导致骨骼肌性能随年龄增长而下降 以及它们的逆转或阻滞， 干预措施。骨骼肌质量、力量和运动相关的减少 和质量被称为肌肉减少症，并可能有助于身体 残疾和丧失独立性。除了质量减少， 已经报道了肌肉收缩力的降低。尽管 肌肉质量和力量在预防残疾方面的重要性， 造成这些现象的生物学机制并不完善， 明白本提案的目的是确定机制， 导致骨骼肌收缩力随年龄增长而下降。 该假设包括（a）机制研究和（B）干预研究。 (a)机械学研究。二氢吡啶受体减少， 老年骨骼肌中的管状肌膜导致供应减少 钙与收缩蛋白质的结合这些功能的后果 细胞内的变化是收缩力的降低。(b)干预 问题研究这些改变可以被显著逆转和延迟， 长期饮食热量限制。我们将探讨这一假设 使用以下具体目标：1）确定 DHPR在离体快缩趾长伸肌中的表达 来自年轻（7个月）、中年（14）和老年（28）的肌纤维 Fisher 344 Brown Norway F1杂交大鼠（F1杂交大鼠 （F344BNF1/NIA）。2)为了评估肌浆细胞的减少是否 网钙释放是由于大量的钙 释放通道（RYR）在老年动物中与DHPR解偶联。3)到 将骨骼肌收缩特性的下降与 细胞内钙浓度的改变。4)建立 肌膜兴奋-收缩偶联的改变 与衰老相关的疾病可以被显著逆转和/或延迟， 饮食热量限制。目前的提案是一部小说 骨骼肌基本机制的表征 年龄的增长，这是以前没有解决的。

The long term goal of this study is to elucidate the mechanism(s) responsible for the decline in skeletal muscle performance with age and their reversion or retardation with non-pharmacological interventions. Age-related decreases in skeletal muscle mass, strength and quality are termed sarcopenia and may contribute to physical disability and loss of independence. In addition to decreased mass, decreases in muscle contractile force has been reported. Despite the importance of muscle mass and strength in preventing disability, the biological mechanisms responsible for these phenomena are poorly understood. The purpose of this proposal is to determine mechanisms responsible for the decline in skeletal muscle contractility with aging. The hypothesis includes (a) mechanistic and (b) intervention studies. (a) Mechanistic studies. A decrease in dihydropyridine receptors at the tubular sarcolemma in aged skeletal muscle results in a reduced supply of calcium to contractile proteins. The functional consequence of these intracellular changes is a decrease in contractile force. (b) Intervention studies. These alterations can be significantly reversed and delayed by long-term dietary caloric restriction. This hypothesis will be explored using the following specific aims: 1) To determine the amount of DHPR expression in isolated fast-twitch extensor digitorum longus muscle fiber from young (7 months), middle age (14), and old (28) Fisher 344 Brown Norway F1 Hybrids rats (F1 Hybrids rats (F344BNF1/NIA). 2) To assess whether reductions in the sarcoplasmic reticulum calcium release is a result of significant number of calcium release channels (RYRs) uncoupled to DHPRs in older animals. 3) To correlate decline in skeletal muscle contraction properties with alterations in intracellular calcium concentrations. 4) To establish whether alterations in sarcolemmal excitation-contraction coupling associated with aging can be significantly reversed and/or delayed by dietary caloric restriction. The current proposal is a novel characterization of the basic mechanisms underlying skeletal muscle impairment with age, which previously have not been addressed.