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Transcriptional Signatures of Aging

机译：老化转录签名

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Genome-wide studies of aging have identified subsets of genes that show age-related changes in expression. Although the types of genes that are age regulated vary among different tissues and organisms, some patterns emerge from these large data sets. First, aging is associated with a broad induction of stress response pathways, although the specific genes and pathways involved differ depending on cell type and species. In contrast, a wide variety of functional classes of genes are downregulated with age, often including tissue-specific genes. Although the upregulation of age-regulated genes is likely to be governed by stress-responsive transcription factors, questions remain as to why particular genes are susceptible to age-related transcriptional decline. Here, we discuss recent findings showing that splicing is misregulated with age. While defects in splicing could lead to changes in protein isoform levels, they could also impact gene expression through nonsense-mediated decay of intron-retained transcripts. The discovery that splicing is misregulated with age suggests that other aspects of gene expression, such as transcription elongation, termination, and polyadenylation, must also be considered as potential mechanisms for age-related changes in transcript levels. Moreover, the considerable variation between genome-wide aging expression studies indicates that there is a critical need to analyze the transcriptional signatures of aging in single-cell types rather than whole tissues. Since age-associated decreases in gene expression could contribute to a progressive decline in cellular function, understanding the mechanisms that determine the aging transcriptome provides a potential target to extend healthy cellular lifespan. (C) 2017 Elsevier Ltd. All rights reserved.
机译：对老化的基因组研究已经确定了表现出表达年龄相关变化的基因子集。虽然年龄调节的基因类型在不同的组织和生物中变化，但是一些模式从这些大数据集中出现。首先，老化与宽诱导应激响应途径的诱导相关，尽管涉及的特定基因和途径根据细胞类型和物种而不同。相反，随着年龄的增长，通常包括组织特异性基因，各种基因的各种功能类别。虽然年龄调节基因的上调可能受到应激响应性转录因素的管辖，但仍然是特定基因易患年龄相关的转录下降的问题。在这里，我们讨论最近的发现表明拼接是随着年龄的增长来误解的。虽然剪接缺陷可能导致蛋白质同种型水平的变化，但它们也可以通过内蒙氏保留的转录物的废话介导的衰减来影响基因表达。拼接的发现具有年龄的发现表明基因表达的其他方面，例如转录伸长，终止和多腺苷酸化，也必须被认为是转录水平的年龄相关变化的潜在机制。此外，基因组 - 宽的老化表达研究的相当大变化表明存在危急需要分析单细胞类型而不是整个组织的老化的转录签名。由于基因表达的年龄相关降低可以有助于细胞功能的逐渐下降，了解确定老化转录组的机制提供延长健康细胞寿命的潜在靶标。 （c）2017 Elsevier Ltd.保留所有权利。

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