Gene expression profiling of aging in multiple mouse strains: identification of aging biomarkers and impact of dietary antioxidants.

Gene expression profiling of aging in multiple mouse strains: identification of aging biomarkers and impact of dietary antioxidants.
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DOI:
10.1111/j.1474-9726.2009.00496.x
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发表时间:
2009-08
期刊:
影响因子:
7.8
通讯作者:
Prolla TA
Prolla TA
中科院分区:
生物学1区
文献类型:
--
作者:
Park SK;Kim K;Page GP;Allison DB;Weindruch R;Prolla TA

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我们使用DNA微阵列来鉴定衰老的转录标记物,这些标记物在多个近交系(129 sv,BALB/c,CBA,DBA,B6,C3 H和B6 C3 F1)的年轻(5个月)和老年(25个月)小鼠中差异表达。在心脏中,在小鼠的整个生命周期中研究了五个基因的年龄相关变化:补体成分4,趋化因子配体14,Sp100-rs,苯丙氨酸羟化酶和src家族相关磷蛋白2的组成部分。脑(小脑)中的类似分析涉及补体成分1 q(α多肽)、补体成分4、P溶菌酶结构、神经胶质细胞酸性蛋白和组织蛋白酶S。热量限制抑制了这些基因在两种组织中与年龄相关的表达。基因集富集(PAGE)的参数分析,确定了几个生物过程中诱导的衰老在多个小鼠品系。我们还测试了膳食抗氧化剂对抗这些衰老转录标志物的能力。番茄红素、白藜芦醇、乙酰-L-肉碱和Tempol在心脏中与热量限制一样有效,α-硫辛酸和辅酶Q10在小脑中与热量限制一样有效。这些发现表明,小鼠衰老的转录生物标志物可用于评估组织特异性基础上的衰老干预措施的疗效。
We used DNA microarrays to identify panels of transcriptional markers of aging that are differentially expressed in young (5-month) and old (25-month) mice of multiple inbred strains (129sv, BALB/c, CBA, DBA, B6, C3H, and B6C3F1). In the heart, age-related changes of five genes were studied throughout the mouse lifespan: complement component 4, chemokine ligand 14, component of Sp100-rs, phenylalanine hydroxylase, and src family associated phosphoprotein 2. A similar analysis in the brain (cerebellum) involved complement component 1q (alpha polypeptide), complement component 4, P lysozyme structural, glial fibrillary acidic protein, and cathepsin S. Caloric restriction inhibited age-related expression of these genes in both tissues. Parametric analysis of gene set enrichment (PAGE) identified several biological processes that are induced with aging in multiple mouse strains. We also tested the ability of dietary antioxidants to oppose these transcriptional markers of aging. Lycopene, resveratrol, acetyl-L-carnitine, and Tempol were as effective as caloric restriction in the heart, and α-lipoic acid and coenzyme Q10 were as effective as caloric restriction in the cerebellum. These findings suggest that transcriptional biomarkers of aging in mice can be used to estimate the efficacy of aging interventions on a tissue-specific basis.
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