In vivo spectrofluorimetry reveals endogenous biomarkers that report healthspan and dietary restriction in Caenorhabditis elegans
In vivo spectrofluorimetry reveals endogenous biomarkers that report healthspan and dietary restriction in Caenorhabditis elegans
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DOI：
10.1111/j.1474-9726.2005.00153.x
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发表时间：
2005-06-01
期刊：
影响因子：
7.8
通讯作者：
Driscoll, M
中科院分区：
文献类型：
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作者：
Gerstbrein, B;Stamatas, G;Driscoll, M
自体荧光脂褐素和晚期糖基化终产物（老年色素）随着年龄的增长而在各个门中积累，但对它们在生理条件下的形成及其对衰老过程的具体贡献知之甚少。我们在体内使用荧光分光光度法定量自发荧光野生型秀丽隐杆线虫和长寿突变体破坏不同方面的老化过程。在野生型动物中，年龄色素增加到成年期，在生殖阶段缓慢积累，在生殖后阶段积累得更快。与人类一样，胰岛素信号传导影响老年色素积累-降低胰岛素信号传导功效并延长寿命的突变[daf-2（e1370）胰岛素受体和age-1（hx 546）PI 3-激酶]显著降低老年色素积累;相反地，胰岛素抑制的α-16/FOXO转录因子的消除导致老年色素积累的巨大增加，支持了短寿命的DAF-16无效突变体确实是早老性的。相比之下，增加线粒体活性氧产生的突变不会影响老年色素的积累，挑战了关于氧化应激在体内产生这些物质中的作用的假设。饮食限制显着降低年龄色素水平，并与一个独特的光谱变化，可能作为一个快速评分的报告者的饮食限制状态。出乎意料的是，年龄不佳的基因相同的兄弟姐妹（根据衰老的运动能力来判断）的年龄色素水平明显高于同龄的兄弟姐妹，后者似乎年龄更优雅，行动更年轻。因此，高年龄色素水平表明生理老化状态，而不是简单地标记按时间顺序排列的时间，年龄色素是线虫健康寿命的有效报告。
Autofluorescent lipofuscin and advanced glycation end-products (age pigments) accumulate with age across phyla, yet little is understood about their formation under physiological conditions and their specific contributions to the aging process. We used in vivo spectrofluorimetry to quantitate autofluorescence in wild-type Caenorhabditis elegans and longevity mutants disrupted for distinct aspects of the aging process. In wild-type animals, age pigments increase into adulthood, accumulating slowly during the reproductive phase and more rapidly during the post-reproductive period. As in humans, insulin signaling influences age pigment accumulation - mutations that lower efficacy of insulin signaling and extend lifespan [daf-2(e1370) insulin receptor and age-1(hx546) PI3-kinase] dramatically lower age pigment accumulation; conversely, elimination of the insulin-inhibited DAF-16/FOXO transcription factor causes a huge increase in age pigment accumulation, supporting that the short-lived daf-16 null mutant is truly progeric. By contrast, mutations that increase mitochondrial reactive oxygen species production do not affect age pigment accumulation, challenging assumptions about the role of oxidative stress in generating these species in vivo. Dietary restriction reduces age pigment levels significantly and is associated with a unique spectral shift that might serve as a rapidly scored reporter of the dietary restricted state. Unexpectedly, genetically identical siblings that age poorly (as judged by decrepit locomotory capacity) have dramatically higher levels of age pigments than their same-aged siblings that appear to have aged more gracefully and move youthfully. Thus, high age pigment levels indicate a physiologically aged state rather than simply marking chronological time, and age pigments are valid reporters of nematode healthspan.