Proteomic analysis of age-dependent changes in protein solubility identifies genes that modulate lifespan.
Proteomic analysis of age-dependent changes in protein solubility identifies genes that modulate lifespan.
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DOI：
10.1111/j.1474-9726.2011.00765.x
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发表时间：
2012-02
期刊：
影响因子：
7.8
通讯作者：
Hughes RE
中科院分区：
文献类型：
--
作者：
Reis-Rodrigues P;Czerwieniec G;Peters TW;Evani US;Alavez S;Gaman EA;Vantipalli M;Mooney SD;Gibson BW;Lithgow GJ;Hughes RE
虽然人们普遍认为特定蛋白质的错误折叠可能导致迟发性疾病，但蛋白质聚集对正常衰老过程的贡献尚不清楚。为了解决这个问题，我们进行了基于质谱的蛋白质组学分析，以鉴定秀丽隐杆线虫衰老过程中采用十二烷基硫酸钠 (SDS) 不溶性构象的蛋白质。从年轻和年老的秀丽隐杆线虫中提取的 SDS 不溶性蛋白质通过同量异位标签进行化学标记，进行相对和绝对定量 (iTRAQ)，并通过液相色谱和质谱进行鉴定。鉴定出 203 种蛋白质在年老线虫的 SDS 不溶部分中显着富集，而在年轻线虫的类似蛋白质部分中基本上不存在。老年动物中的 SDS 不溶部分含有多种蛋白质，包括大量核糖体蛋白质。基因本体分析揭示了能量产生和翻译功能的高度显着丰富。使用 RNAi 敲低衰老线虫中观察到的编码不溶性蛋白质的基因的表达，并测量对寿命的影响。 41% 的测试基因在 RNAi 治疗后被证明可以延长寿命，而对照组基因的这一比例为 18%。这些数据表明，编码随着年龄的增长而变得不溶的蛋白质的基因对于寿命调节剂的作用丰富。这表明蛋白质组学方法可用于识别改变寿命的基因。最后，这些观察结果表明，具有不同功能的不溶性蛋白质的积累可能是衰老的普遍特征。
While it is generally recognized that misfolding of specific proteins can cause late-onset disease, the contribution of protein aggregation to the normal aging process is less well understood. To address this issue, a mass spectrometry-based proteomic analysis was performed to identify proteins that adopt sodium dodecyl sulfate (SDS)-insoluble conformations during aging in Caenorhabditis elegans. SDS-insoluble proteins extracted from young and aged C. elegans were chemically labeled by isobaric tagging for relative and absolute quantification (iTRAQ) and identified by liquid chromatography and mass spectrometry. Two hundred and three proteins were identified as being significantly enriched in an SDS-insoluble fraction in aged nematodes and were largely absent from a similar protein fraction in young nematodes. The SDS-insoluble fraction in aged animals contains a diverse range of proteins including a large number of ribosomal proteins. Gene ontology analysis revealed highly significant enrichments for energy production and translation functions. Expression of genes encoding insoluble proteins observed in aged nematodes was knocked down using RNAi, and effects on lifespan were measured. 41% of genes tested were shown to extend lifespan after RNAi treatment, compared with 18% in a control group of genes. These data indicate that genes encoding proteins that become insoluble with age are enriched for modifiers of lifespan. This demonstrates that proteomic approaches can be used to identify genes that modify lifespan. Finally, these observations indicate that the accumulation of insoluble proteins with diverse functions may be a general feature of aging.
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影响因子：
9.8
作者：
David DC;Ollikainen N;Trinidad JC;Cary MP;Burlingame AL;Kenyon C
通讯作者：
Kenyon C
影响因子：
7.8
作者：
Walker, GA;Lithgow, GJ
通讯作者：
Lithgow, GJ
影响因子：
64.8
作者：
Ogg, S;Paradis, S;Ruvkun, G
通讯作者：
Ruvkun, G
DOI：
10.1093/gerona/56.7.b281
发表时间：
2001-07-01
影响因子：
5.1
作者：
Walker, GA;White, TM;Lithgow, GJ
通讯作者：
Lithgow, GJ
DOI：
10.1073/pnas.92.20.9368
发表时间：
1995-09-26
影响因子：
11.1
作者：
LINK, CD
通讯作者：
LINK, CD