MicroRNA Expression in Aging Mice and in Models of Longevity

衰老小鼠和长寿模型中的 MicroRNA 表达

• 批准号: 7769510
• 负责人: SUSAN L NAYLOR
• 金额: $ 15.07万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2012-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7769510
• 关键词: Accounting; Adult; Affect; Age; Age-Months; Aging; Caenorhabditis elegans; Caloric Restriction; Computer software; Curiosities; Data; Databases; Development; Disease; Dwarfism; Gene Expression; Gene Expression Regulation; Gene Targeting; Genes; Genetic; Institutes; Insulin; Kidney; Life; Ligands; Liver; Longevity; Mammals; Measures; Messenger RNA; MicroRNAs; Microarray Analysis; Modeling; Molecular; Molecular Profiling; Mus; Muscle; Process; Research; Reverse Transcriptase Polymerase Chain Reaction; Rodent; Role; Skeletal Muscle; Small RNA; Testing; Time; Tissue Sample; Tissues; Translational Regulation; Western Blotting; Wild Type Mouse; age related; anti aging; design; dietary restriction; feeding; insight; middle age; mimetics; mouse model; programs; public health relevance; research study; young adult

DESCRIPTION (provided by applicant): The long term objective of this research is to identify the molecular mechanism that accounts for extended lifespan. Two mouse models of extended lifespan will be studied: Caloric restriction and the Ames dwarf mouse. It has been known for decades that caloric restriction in rodents leads to significantly increased lifespan. Likewise, dwarf mice such as the Ames mouse also have a prolonged lifespan. MicroRNAs are likely potential candidates for molecules that regulate lifespan as one of these small RNAs (~22 nt) can control the expression of multiple genes. To determine if miRNAs have a role in aging three specific aims are proposed. Specific aim 1 is to establish the miRNA profile of normal mice at young adulthood, middle age and old age using microarray technology to determine if specific miRNAs correlate with age. miRNA microarray data will be validated by real-time reverse transcriptase PCR. Specific aim 2 will determine the miRNA profile of the long lived caloric restricted mouse to examine if there are specific miRNA correlated with longer lifespan. Specific aim 3 will examine the miRNA profile of the Ames dwarf mouse which is not considered to be a mimetic of caloric restriction. Comparison of the extended lifespan models will indicate if there are specific miRNAs in common that contribute to increased lifespan. The identification of such a regulatory molecule will help unlock the mechanism of controlling lifespan in mammals PUBLIC HEALTH RELEVANCE: Aging is a normal process of life but it is still unknown what mechanism instigates intrinsic aging. If we understand this process, we may be able to delay age- related changes especially those related to age-dependent disease. Understanding models of prolonged lifespan will yield clues into the process and may give insight into how we can age in a more healthy manner.

描述（由申请人提供）：这项研究的长期目标是确定延长寿命的分子机制。将研究两种延长寿命的小鼠模型：热量限制和AMES矮人小鼠。几十年来，啮齿动物的热量限制会导致寿命显着增加。同样，矮小的小鼠（例如Ames Mouse）的寿命也延长。 MicroRNA可能是调节寿命作为这些小RNA（〜22 nt）之一的分子的潜在候选物，可以控制多个基因的表达。为了确定miRNA是否在老化中起作用，提出了三个特定目标。具体目标1是使用微阵列技术在成年，中年和老年时建立正常小鼠的miRNA谱，以确定特定的miRNA是否与年龄相关。 miRNA微阵列数据将通过实时逆转录酶PCR验证。特定的目标2将确定长期寿命限制的小鼠的miRNA谱，以检查特定的miRNA是否与更长的寿命相关。特定的目标3将检查AMES矮小鼠的miRNA谱，这不被认为是热量限制的模拟物。扩展寿命模型的比较将指示是否有特定的miRNA有助于增加寿命。这种调节分子的识别将有助于释放哺乳动物公共卫生相关性控制寿命的机制：衰老是一种正常的生活过程，但仍不知道哪种机制促进了内在的衰老。如果我们了解这一过程，我们可能会延迟与年龄相关的变化，尤其是与年龄依赖性疾病有关的变化。了解延长寿命的模型将为这一过程带来线索，并可以深入了解我们如何以更健康的方式老化。