Transcriptional profiling of MnSOD-mediated lifespan extension in Drosophila reveals a species-general network of aging and metabolic genes.
Transcriptional profiling of MnSOD-mediated lifespan extension in Drosophila reveals a species-general network of aging and metabolic genes.
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DOI：
10.1186/gb-2007-8-12-r262
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发表时间：
2007
期刊：
影响因子：
12.3
通讯作者：
Tower J
中科院分区：
文献类型：
--
作者：
Curtis C;Landis GN;Folk D;Wehr NB;Hoe N;Waskar M;Abdueva D;Skvortsov D;Ford D;Luu A;Badrinath A;Levine RL;Bradley TJ;Tavaré S;Tower J
果蝇MnSOD介导的寿命延长的转录谱确定了一组候选的衰老生物标志物，主要包括碳水化合物代谢和电子传递基因。几种干预措施增加了模型生物的寿命，包括减少胰岛素/胰岛素样生长因子样信号（IIS），FOXO转录因子激活，饮食限制和超氧化物歧化酶（SOD）过表达。一个问题是，这些操作是否通过不同的机制发挥作用，或者它们是否在影响衰老的共同过程中相互交叉。一个多西环素调节系统被用来过表达锰-SOD（MnSOD）在成年果蝇，产生的平均和最大寿命增加20%。寿命的增加是由于降低了初始死亡率，并需要MnSOD在成人中过表达。转录分析表明，特定基因的表达被改变MnSOD在正常衰老过程中的模式相反的方式，揭示了一组候选生物标志物的老化丰富的碳水化合物代谢和电子传递基因，并建议在生理老化的真正延迟，而不是一个新的表型。引人注目的是，交叉数据集比较表明，MnSOD引起的基因表达模式与在长寿的秀丽隐杆线虫胰岛素样信号突变体和外源性应激反应中观察到的相似，从而暴露了潜在的保守的长寿促进基因，并暗示了果蝇长寿的解毒作用。这些数据表明，MnSOD上调和来自线粒体的活性氧物质的逆行信号通常在各种物种中作为由胰岛素样信号传导减少引起的寿命延长的中间步骤起作用。这些结果暗示了一个物种保守的协调基因网络，这些基因通过调节能量效率、嘌呤生物合成、凋亡途径、内分泌信号以及代谢物的解毒和排泄来影响衰老速率。
Transcriptional profiling of MnSOD-mediated life-span extension in Drosophila identifies a set of candidate biomarkers of aging, consisting primarily of carbohydrate metabolism and electron transport genes. Several interventions increase lifespan in model organisms, including reduced insulin/insulin-like growth factor-like signaling (IIS), FOXO transcription factor activation, dietary restriction, and superoxide dismutase (SOD) over-expression. One question is whether these manipulations function through different mechanisms, or whether they intersect on common processes affecting aging. A doxycycline-regulated system was used to over-express manganese-SOD (MnSOD) in adult Drosophila, yielding increases in mean and maximal lifespan of 20%. Increased lifespan resulted from lowered initial mortality rate and required MnSOD over-expression in the adult. Transcriptional profiling indicated that the expression of specific genes was altered by MnSOD in a manner opposite to their pattern during normal aging, revealing a set of candidate biomarkers of aging enriched for carbohydrate metabolism and electron transport genes and suggesting a true delay in physiological aging, rather than a novel phenotype. Strikingly, cross-dataset comparisons indicated that the pattern of gene expression caused by MnSOD was similar to that observed in long-lived Caenorhabditis elegans insulin-like signaling mutants and to the xenobiotic stress response, thus exposing potential conserved longevity promoting genes and implicating detoxification in Drosophila longevity. The data suggest that MnSOD up-regulation and a retrograde signal of reactive oxygen species from the mitochondria normally function as an intermediate step in the extension of lifespan caused by reduced insulin-like signaling in various species. The results implicate a species-conserved net of coordinated genes that affect the rate of senescence by modulating energetic efficiency, purine biosynthesis, apoptotic pathways, endocrine signals, and the detoxification and excretion of metabolites.
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影响因子：
7.8
作者：
Curtis, R;O'Connor, G;DiStefano, PS
通讯作者：
DiStefano, PS
DOI：
10.1073/pnas.0405775102
发表时间：
2005-02-22
影响因子：
11.1
作者：
Broughton, SJ;Piper, MDW;Partridge, L
通讯作者：
Partridge, L
DOI：
10.1002/neu.20193
发表时间：
2006-01-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Belgacem, YH;Martin, JR
通讯作者：
Martin, JR
影响因子：
3.9
作者：
Ford, Daniel;Hoe, Nicholas;Tower, John
通讯作者：
Tower, John
影响因子：
5.8
作者：
Beissbarth, T;Speed, TP
通讯作者：
Speed, TP