Identifying Critical Molecular Targets to Suppress Age-Related Muscle Fiber Loss

识别关键分子靶标以抑制与年龄相关的肌纤维损失

• 批准号: 8772675
• 负责人: Anton Bryantsev
• 金额: $ 7.55万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8772675
• 关键词: Animal Model; Architecture; Cells; Characteristics; Complex; Development; Diagnostic; Drosophila melanogaster; Elderly; Event; Excision; Fiber; Gene Expression; Gene Expression Profile; Genes; Genetic; Genetic Programming; Goals; Health; Health Care Costs; Human; Individual; Knowledge; Link; Longevity; Mediating; Microscopic; Mission; Molecular; Molecular Target; Morbidity - disease rate; Muscle; Muscle Fibers; Muscle Proteins; Muscle Weakness; Nature; Outcome; Population; Population Study; Process; Quality of life; Reporter; Research; Resistance; Testing; Therapeutic; Transcription Repressor/Corepressor; Troponin; Variant; Work; age related; base; derepression; gene interaction; genetic variant; genome-wide; mortality; muscle aging; muscle form; novel; prevent; prophylactic; public health relevance; sarcopenia; skeletal; wasting

DESCRIPTION (provided by applicant): The progressive wasting of skeletal muscle mass (sarcopenia) is a wide-spread, age-related pathological condition found in the modern elderly populations. The loss of muscle mass, paralleled by progressive muscular weakness, deteriorates the quality of living among the elderly, coincides with increased mortality and morbidity rates, and has an estimated healthcare cost of billions of dollars. Age-related muscle mass loss is reflected by microscopic changes in the muscle architecture, where loss of individual muscle fibers is one of the characteristic events. The nature and molecular mechanisms underlying age-related fiber loss (ARFL) and muscle wasting are apparently complex and currently not well understood. Thus, there is an urgent need for identification of a broad range of molecular targets that influence the rate of ARFL in aging muscles. This information will become critical in developing prophylactic and therapeutic approaches to curb age-related muscle wasting. My long-term goal is to identify genetic factors and molecular mechanisms that prolong healthy lifespan of muscles. The objectives here are to identify a range of muscle genes whose activity could be associated with increased resistance against ARFL. My central hypothesis is that greater muscle resistance to ARFL can be achieved cell-autonomously, through changes in muscle transcriptome, specifically by up- regulating expression of genes encoding structural muscle proteins. The expected outcome of this proposed project is an expansion in the list of genes and gene interactions essential to provide tolerance against age- related fiber degeneration and loss. These results will have a positive impact on human health as they will supply novel candidates for developing diagnostic and therapeutic approaches to detect and abrogate molecular processes leading to development of sarcopenia.

描述（由申请人提供）：骨骼肌质量进行性萎缩（肌少症）是现代老年人口中发现的一种广泛存在的、与年龄相关的病理状况。肌肉质量的丧失，伴随着进行性肌肉无力，会恶化老年人的生活质量，同时死亡率和发病率也会增加，并且估计会造成数十亿美元的医疗费用。与年龄相关的肌肉质量损失通过肌肉结构的微观变化反映出来，其中单个肌纤维的损失是特征事件之一。年龄相关纤维损失（ARFL）和肌肉萎缩的本质和分子机制显然很复杂，目前尚未得到很好的了解。因此，迫切需要确定影响衰老肌肉 ARFL 发生率的广泛分子靶点。这些信息对于开发遏制与年龄相关的肌肉萎缩的预防和治疗方法至关重要。我的长期目标是确定延长肌肉健康寿命的遗传因素和分子机制。这里的目标是确定一系列肌肉基因，其活性可能与 ARFL 抵抗力的增强相关。我的中心假设是，通过改变肌肉转录组，特别是通过上调编码结构肌肉蛋白的基因的表达，可以细胞自主地实现对 ARFL 的更大的肌肉抵抗力。该拟议项目的预期结果是扩展基因和基因相互作用的列表，这些基因和基因相互作用对于提供对与年龄相关的纤维变性和损失的耐受性至关重要。这些结果将对人类健康产生积极影响，因为它们将为开发诊断和治疗方法来检测和消除导致肌肉减少症发展的分子过程提供新的候选者。