MICRORNA EXPRESSION IN AGING: EFFECTS OF EXERCISE AND ESSENTIAL AMINO ACIDS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 众所周知，随着个体年龄的增长，肌肉质量下降。抗阻运动和氨基酸似乎是值得在老年人中使用的干预措施，以防止肌肉质量的损失。 最近的发现已经导致鉴定出具有抑制蛋白质合成能力的microRNA。 因此，microRNA对骨骼肌生长的调控可能是老年人和抗阻运动后氨基酸调控骨骼肌生长的新机制。 基于目前的文献，我们的一般假设是microRNA在老年骨骼肌中上调。 我们还假设microRNA在年轻和老年骨骼肌的抗阻运动和氨基酸摄入的恢复期下调，但这种反应在年轻骨骼肌中更大。我们将测量年轻和老年受试者中microRNA 1、133 a和206的基础水平，并确定在单次抗阻运动或必需氨基酸后的恢复期内，年轻和老年受试者中microRNA 1、133 a和206是否上调或下调以及差异调节。我们将研究20名年轻男性（18- 40岁）和20名老年男性（60 - 85岁）。 肌肉活检（~150 mg）将用于测量混合肌肉蛋白质合成、细胞内富集、氨基酸浓度和microRNA表达。肌肉质量的减少可导致骨折和福尔斯的增加以及伴随的独立性丧失和随后的死亡率增加。 因此，必须制定干预措施，以防止和/或减缓这种下降。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. It is well known that as an individual ages muscle mass declines. Resistance exercise and amino acids appears to be worthwhile interventions to use in the elderly to prevent the loss in muscle mass. Recent discoveries have led to the identification of microRNAs that have the ability to repress protein synthesis. Thus, the regulation of skeletal muscle growth by microRNAs may be a novel mechanisms to explore in the aged and after resistance exercise and amino acids. Based on the current literature our general hypothesis is that microRNAs are upregulated in older skeletal muscle. We also hypothesize microRNAs to be downregulated during the recovery period of resistance exercise and amino acids ingestion in young and old skeletal muscle but this response will be greater in young skeletal muscle. We will measure basal levels of microRNA 1, 133a and 206 in young and old subjects and determine if microRNA 1, 133a and 206 are up or downregulated and differentiallyregulated in young vs. old subjects during the recovery period after a single bout of resistance exercise or essential amino acids. We will study 20 young men (18-40y) and 20 old men (60 to 85y). Muscle biopsy (~150 mg) will be used to measure mixed muscle protein synthesis, intracellular enrichment, amino acid concentration, and microRNA expression. Reductions in muscle mass can lead to an increase in fractures and falls and an accompanied loss of independence and subsequent increase in mortality. Thus it is imperative to develop interventions to prevent and/or attenuate this decline.