MicroRNA Expression in Aging Mice and in Models of Longevity

描述（由申请人提供）：本研究的长期目标是确定延长寿命的分子机制。两种延长寿命的小鼠模型将被研究：热量限制和艾姆斯矮鼠。几十年来，人们都知道啮齿动物的热量限制会显著延长寿命。同样，像艾姆斯老鼠这样的侏儒老鼠也有较长的寿命。MicroRNAs可能是调节寿命的潜在候选分子，因为这些小rna（约22 nt）之一可以控制多个基因的表达。为了确定mirna是否在衰老中起作用，提出了三个特定的目标。具体目的1是利用微阵列技术建立正常小鼠在青年期、中年期和老年期的miRNA谱，以确定特定miRNA是否与年龄相关。miRNA微阵列数据将通过实时逆转录酶PCR进行验证。特异性目标2将确定长寿命热量限制小鼠的miRNA谱，以检查是否存在与更长的寿命相关的特异性miRNA。具体目标3将检查不被认为是模拟热量限制的Ames矮鼠的miRNA谱。延长寿命模型的比较将表明是否有特定的共同mirna有助于延长寿命。公共卫生相关性：衰老是一种正常的生命过程，但究竟是什么机制引发了内在衰老，目前尚不清楚。如果我们了解这个过程，我们可能能够延缓与年龄有关的变化，特别是那些与年龄相关的疾病。了解延长寿命的模型将为这一过程提供线索，并可能让我们了解如何以更健康的方式变老。

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.