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在秀丽隐杆线虫中,与年龄相关的行为具有独特的转录谱。

Age-related behaviors have distinct transcriptional profiles in Caenorhabditis elegans.

作者信息

Golden Tamara R, Hubbard Alan, Dando Caroline, Herren Michael A, Melov Simon

机构信息

Buck Institute for Age Research, Novato, CA 94945, USA.

出版信息

Aging Cell. 2008 Dec;7(6):850-65. doi: 10.1111/j.1474-9726.2008.00433.x.

Abstract

There has been a great deal of interest in identifying potential biomarkers of aging. Biomarkers of aging would be useful to predict potential vulnerabilities in an individual that may arise well before they are chronologically expected, due to idiosyncratic aging rates that occur between individuals. Prior attempts to identify biomarkers of aging have often relied on the comparisons of long-lived animals to a wild-type control. However, the effect of interventions in model systems that prolong lifespan (such as single gene mutations or caloric restriction) can sometimes be difficult to interpret due to the manipulation itself having multiple unforeseen consequences on physiology, unrelated to aging itself. The search for predictive biomarkers of aging therefore is problematic, and the identification of metrics that can be used to predict either physiological or chronological age would be of great value. One methodology that has been used to identify biomarkers for numerous pathologies is gene expression profiling. Here, we report whole-genome expression profiles of individual wild-type Caenorhabditis elegans covering the entire wild-type nematode lifespan. Individual nematodes were scored for either age-related behavioral phenotypes, or survival, and then subsequently associated with their respective gene expression profiles. This facilitated the identification of transcriptional profiles that were highly associated with either physiological or chronological age. Overall, our approach serves as a paradigm for identifying potential biomarkers of aging in higher organisms that can be repeatedly sampled throughout their lifespan.

摘要

人们对识别衰老的潜在生物标志物有着浓厚的兴趣。衰老的生物标志物对于预测个体可能出现的潜在脆弱性很有用,这些脆弱性可能在按时间顺序预期之前就出现,这是由于个体之间存在的特殊衰老速率。先前识别衰老生物标志物的尝试通常依赖于将长寿动物与野生型对照进行比较。然而,在延长寿命的模型系统中(如单基因突变或热量限制)进行干预的效果有时难以解释,因为这种操作本身会对生理产生多种不可预见的后果,而这些后果与衰老本身无关。因此,寻找衰老的预测性生物标志物存在问题,而识别可用于预测生理年龄或时间年龄的指标将具有重要价值。一种已被用于识别多种病理生物标志物的方法是基因表达谱分析。在此,我们报告了覆盖整个野生型线虫寿命的单个野生型秀丽隐杆线虫的全基因组表达谱。对单个线虫进行与年龄相关的行为表型或存活率评分,然后将其与各自的基因表达谱相关联。这有助于识别与生理年龄或时间年龄高度相关的转录谱。总体而言,我们的方法为识别高等生物中衰老的潜在生物标志物提供了一个范例,这些生物标志物可以在其整个寿命期间反复采样。

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