The effects of graded levels of calorie restriction: XI. Evaluation of the main hypotheses underpinning the life extension effects of CR using the hepatic transcriptome.
The effects of graded levels of calorie restriction: XI. Evaluation of the main hypotheses underpinning the life extension effects of CR using the hepatic transcriptome.
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DOI：
10.18632/aging.101269
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发表时间：
2017-07-31
期刊：
影响因子：
--
通讯作者：
Speakman JR
中科院分区：
文献类型：
--
作者：
Derous D;Mitchell SE;Wang L;Green CL;Wang Y;Chen L;Han JJ;Promislow DEL;Lusseau D;Douglas A;Speakman JR
热量限制（CR）可以通过调节衰老机制来延长寿命。对于其主要作用方式，人们提出了不同的假说。我们量化了雄性C57 BL/6小鼠暴露于分级CR水平（0%至40%CR）三个月的肝脏转录物，并评估了相对于这些不同假设的反应。在暗示与CR对寿命的影响相关的四种主要信号传导途径（胰岛素/胰岛素样生长因子1（IGF-1）、核因子-κ β（NF-κ B）、雷帕霉素的机制靶标（mTOR）和沉默调节蛋白（SIRT））中，除SIRT外的所有途径都以与寿命增加一致的方式改变。SIRT 4和SIRT 7的表达水平随着CR水平的升高而降低。CR下与燃料利用率改变一致的变化可能会减少活性氧物质的产生，这与保护的减少是平行的。下调主要尿蛋白（MUP）转录表明减少生殖投资。分级CR对自噬和异生物质代谢具有积极作用，并且对癌症信号传导具有保护作用。CR对成纤维细胞生长因子-21（FGF 21）转录没有显著影响，但影响硫化氢产生途径中的转录。对CR的反应与几种不同的假设一致，CR对寿命的益处可能反映了对多种衰老相关过程的综合影响。
Calorie restriction (CR) may extend longevity by modulating the mechanisms involved in aging. Different hypotheses have been proposed for its main mode of action. We quantified hepatic transcripts of male C57BL/6 mice exposed to graded levels of CR (0% to 40% CR) for three months, and evaluated the responses relative to these various hypotheses. Of the four main signaling pathways implied to be linked to the impact of CR on lifespan (insulin/insulin like growth factor 1 (IGF-1), nuclear factor-kappa beta (NF-ĸB), mechanistic target of rapamycin (mTOR) and sirtuins (SIRTs)), all the pathways except SIRT were altered in a manner consistent with increased lifespan. However, the expression levels of SIRT4 and SIRT7 were decreased with increasing levels of CR. Changes consistent with altered fuel utilization under CR may reduce reactive oxygen species production, which was paralleled by reduced protection. Downregulated major urinary protein (MUP) transcription suggested reduced reproductive investment. Graded CR had a positive effect on autophagy and xenobiotic metabolism, and was protective with respect to cancer signaling. CR had no significant effect on fibroblast growth factor-21 (FGF21) transcription but affected transcription in the hydrogen sulfide production pathway. Responses to CR were consistent with several different hypotheses, and the benefits of CR on lifespan likely reflect the combined impact on multiple aging related processes.
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影响因子：
4.8
作者：
Chiku, Taurai;Padovani, Dominique;Banerjee, Ruma
通讯作者：
Banerjee, Ruma
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
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作者：
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通讯作者：
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DOI：
10.18632/aging.100895
发表时间：
2016-04
期刊：
Aging
影响因子：
--
作者：
Derous D;Mitchell SE;Green CL;Chen L;Han JD;Wang Y;Promislow DE;Lusseau D;Speakman JR;Douglas A
通讯作者：
Douglas A
DOI：
10.1093/gerona/60.1.28
发表时间：
2005-01-01
影响因子：
5.1
作者：
Argentino, DP;Dominici, FP;Turyn, D
通讯作者：
Turyn, D
DOI：
10.1016/0925-4439(95)00024-x
发表时间：
1995-05-24
影响因子：
6.2
作者：
AMES, BN;SHIGENAGA, MK;HAGEN, TM
通讯作者：
HAGEN, TM