摘要
<p class="MsoNoSpacing"><span lang="EN-US" style="font-size:12.0pt"><span style="background:white"><span style="font-family:"Arial","sans-serif""><span style="color:#1c1d1e">Exposure to sub-lethal levels of stress, or hormesis, was a means to induce longevity. By screening for mutations that enhance resistance to multiple stresses, we identified multiple alleles of </span></span></span></span><i style="box-sizing:border-box; font-variant-ligatures:normal; font-variant-caps:normal; orphans:2; text-align:start; widows:2; -webkit-text-stroke-width:0px; text-decoration-thickness:initial; text-decoration-style:initial; text-decoration-color:initial; word-spacing:0px">alpha-1,2-mannosidase I</i><span style="font-variant-ligatures:normal; text-align:start; -webkit-text-stroke-width:0px"><span style="font-variant-caps:normal"><span style="orphans:2"><span style="widows:2"><span style="text-decoration-thickness:initial"><span style="text-decoration-style:initial"><span style="text-decoration-color:initial"><span style="float:none"><span style="word-spacing:0px"> (</span></span></span></span></span></span></span></span></span><i style="box-sizing:border-box; font-variant-ligatures:normal; font-variant-caps:normal; orphans:2; text-align:start; widows:2; -webkit-text-stroke-width:0px; text-decoration-thickness:initial; text-decoration-style:initial; text-decoration-color:initial; word-spacing:0px">mas1</i><span style="font-variant-ligatures:normal; text-align:start; -webkit-text-stroke-width:0px"><span style="font-variant-caps:normal"><span style="orphans:2"><span style="widows:2"><span style="text-decoration-thickness:initial"><span style="text-decoration-style:initial"><span style="text-decoration-color:initial"><span style="float:none"><span style="word-spacing:0px">) which, in addition to promoting stress resistance, also extended longevity. Longevity enhancement is also observed when </span></span></span></span></span></span></span></span></span><i style="box-sizing:border-box; font-variant-ligatures:normal; font-variant-caps:normal; orphans:2; text-align:start; widows:2; -webkit-text-stroke-width:0px; text-decoration-thickness:initial; text-decoration-style:initial; text-decoration-color:initial; word-spacing:0px">mas1</i><span style="font-variant-ligatures:normal; text-align:start; -webkit-text-stroke-width:0px"><span style="font-variant-caps:normal"><span style="orphans:2"><span style="widows:2"><span style="text-decoration-thickness:initial"><span style="text-decoration-style:initial"><span style="text-decoration-color:initial"><span style="float:none"><span style="word-spacing:0px"> expression is reduced via RNA interference in both </span></span></span></span></span></span></span></span></span><i style="box-sizing:border-box; font-variant-ligatures:normal; font-variant-caps:normal; orphans:2; text-align:start; widows:2; -webkit-text-stroke-width:0px; text-decoration-thickness:initial; text-decoration-style:initial; text-decoration-color:initial; word-spacing:0px">Drosophila melanogaster</i><span style="font-variant-ligatures:normal; text-align:start; -webkit-text-stroke-width:0px"><span style="font-variant-caps:normal"><span style="orphans:2"><span style="widows:2"><span style="text-decoration-thickness:initial"><span style="text-decoration-style:initial"><span style="text-decoration-color:initial"><span style="float:none"><span style="word-spacing:0px"> and </span></span></span></span></span></span></span></span></span><i style="box-sizing:border-box; font-variant-ligatures:normal; font-variant-caps:normal; orphans:2; text-align:start; widows:2; -webkit-text-stroke-width:0px; text-decoration-thickness:initial; text-decoration-style:initial; text-decoration-color:initial; word-spacing:0px">Caenorhabditis elegans.</i><span style="font-variant-ligatures:normal; text-align:start; -webkit-text-stroke-width:0px"><span style="font-variant-caps:normal"><span style="orphans:2"><span style="widows:2"><span style="text-decoration-thickness:initial"><span style="text-decoration-style:initial"><span style="text-decoration-color:initial"><span style="float:none"><span style="word-spacing:0px"> The screen also identified </span></span></span></span></span></span></span></span></span><i style="box-sizing:border-box; font-variant-ligatures:normal; font-variant-caps:normal; orphans:2; text-align:start; widows:2; -webkit-text-stroke-width:0px; text-decoration-thickness:initial; text-decoration-style:initial; text-decoration-color:initial; word-spacing:0px">Edem1</i><span style="font-variant-ligatures:normal; text-align:start; -webkit-text-stroke-width:0px"><span style="font-variant-caps:normal"><span style="orphans:2"><span style="widows:2"><span style="text-decoration-thickness:initial"><span style="text-decoration-style:initial"><span style="text-decoration-color:initial"><span style="float:none"><span style="word-spacing:0px"> (</span></span></span></span></span></span></span></span></span><i style="box-sizing:border-box; font-variant-ligatures:normal; font-variant-caps:normal; orphans:2; text-align:start; widows:2; -webkit-text-stroke-width:0px; text-decoration-thickness:initial; text-decoration-style:initial; text-decoration-color:initial; word-spacing:0px">Edm1</i><span style="font-variant-ligatures:normal; text-align:start; -webkit-text-stroke-width:0px"><span style="font-variant-caps:normal"><span style="orphans:2"><span style="widows:2"><span style="text-decoration-thickness:initial"><span style="text-decoration-style:initial"><span style="text-decoration-color:initial"><span style="float:none"><span style="word-spacing:0px">)</span></span></span></span></span></span></span></span></span><i style="box-sizing:border-box; font-variant-ligatures:normal; font-variant-caps:normal; orphans:2; text-align:start; widows:2; -webkit-text-stroke-width:0px; text-decoration-thickness:initial; text-decoration-style:initial; text-decoration-color:initial; word-spacing:0px">,</i><span style="font-variant-ligatures:normal; text-align:start; -webkit-text-stroke-width:0px"><span style="font-variant-caps:normal"><span style="orphans:2"><span style="widows:2"><span style="text-decoration-thickness:initial"><span style="text-decoration-style:initial"><span style="text-decoration-color:initial"><span style="float:none"><span style="word-spacing:0px"> a gene downstream of </span></span></span></span></span></span></span></span></span><i style="box-sizing:border-box; font-variant-ligatures:normal; font-variant-caps:normal; orphans:2; text-align:start; widows:2; -webkit-text-stroke-width:0px; text-decoration-thickness:initial; text-decoration-style:initial; text-decoration-color:initial; word-spacing:0px">mas1,</i><span style="font-variant-ligatures:normal; text-align:start; -webkit-text-stroke-width:0px"><span style="font-variant-caps:normal"><span style="orphans:2"><span style="widows:2"><span style="text-decoration-thickness:initial"><span style="text-decoration-style:initial"><span style="text-decoration-color:initial"><span style="float:none"><span style="word-spacing:0px"> as a modulator of lifespan. As double mutants for both <i>mas1</i> and <i>Edm1</i> showed no additional longevity enhancement, it appeared that both mutations function within a common pathway to extend lifespan. Molecular analysis of these mutants revealed that the expression of </span></span></span></span></span></span></span></span></span><i style="box-sizing:border-box; font-variant-ligatures:normal; font-variant-caps:normal; orphans:2; text-align:start; widows:2; -webkit-text-stroke-width:0px; text-decoration-thickness:initial; text-decoration-style:initial; text-decoration-color:initial; word-spacing:0px">BiP</i><span style="font-variant-ligatures:normal; text-align:start; -webkit-text-stroke-width:0px"><span style="font-variant-caps:normal"><span style="orphans:2"><span style="widows:2"><span style="text-decoration-thickness:initial"><span style="text-decoration-style:initial"><span style="text-decoration-color:initial"><span style="float:none"><span style="word-spacing:0px">, a putative biomarker of dietary restriction (DR), is down-regulated in response to reductions in </span></span></span></span></span></span></span></span></span><i style="box-sizing:border-box; font-variant-ligatures:normal; font-variant-caps:normal; orphans:2; text-align:start; widows:2; -webkit-text-stroke-width:0px; text-decoration-thickness:initial; text-decoration-style:initial; text-decoration-color:initial; word-spacing:0px">mas1</i><span style="font-variant-ligatures:normal; text-align:start; -webkit-text-stroke-width:0px"><span style="font-variant-caps:normal"><span style="orphans:2"><span style="widows:2"><span style="text-decoration-thickness:initial"><span style="text-decoration-style:initial"><span style="text-decoration-color:initial"><span style="float:none"><span style="word-spacing:0px"> expression. These findings suggested that mutations in </span></span></span></span></span></span></span></span></span><i style="box-sizing:border-box; font-variant-ligatures:normal; font-variant-caps:normal; orphans:2; text-align:start; widows:2; -webkit-text-stroke-width:0px; text-decoration-thickness:initial; text-decoration-style:initial; text-decoration-color:initial; word-spacing:0px">mas1</i><span style="font-variant-ligatures:normal; text-align:start; -webkit-text-stroke-width:0px"><span style="font-variant-caps:normal"><span style="orphans:2"><span style="widows:2"><span style="text-decoration-thickness:initial"><span style="text-decoration-style:initial"><span style="text-decoration-color:initial"><span style="float:none"><span style="word-spacing:0px"> may extend longevity by modulating DR.</span></span></span></span></span></span></span></span></span></p>