<p><span>长寿常见问题解答：长寿研究的初学者指南</span></p><p><span/></p><p><span>嗨！我是</span><span>劳拉德明（</span><span>Laura Deming</span><span>）</span><span>，我经营</span><span>长寿基金会（</span><span>Longevity Fund</span><span>）</span><span>。我花了很多时间思考什么可以增加人类健康的寿命。这是我对初学者领域的概述。请随时</span><span>向我发送</span><span/><span>有关以下内容的</span><span>任何问题</span><span>（只包括姓名和隶属关系）。</span></p><p><span/></p><p><span/><span>原文地址：</span><span>https://www.ldeming.com/longevityfaq</span></p><p/><div class="image-package"><img src="https://upload-images.jianshu.io/upload_images/16057169-70ec96f45a6d8c8e.png" class="uploaded-img" style="min-height:200px;min-width:200px;" width="auto" height="auto"/>
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</span></p><p><span>概述：</span></p><p><span>·</span><span/><span>简介</span><span>：</span></p><p><span>o</span><span/><span>老化研究的基本概念</span></p><p><span>·</span><span/><span>说明</span><span>：</span></p><p><span>o</span><span/><span>衰老研究的主要领域</span></p><p><span>§</span><span/><span>热量限制</span></p><p><span>§</span><span/><span>胰岛素</span><span>/ IGF</span></p><p><span>§</span><span/><span>共生</span></p><p><span>§</span><span/><span>衰老</span></p><p><span>§</span><span/><span>自噬</span></p><p><span>§</span><span/><span>下丘脑</span></p><p><span>§</span><span/><span>生殖系统</span></p><p><span>§</span><span/><span>线粒体</span></p><p><span>§</span><span/><span>西尔图因斯</span></p><p><span>·</span><span/><span>资料</span><span>：</span></p><p><span>o</span><span/><span>综合寿命调查</span></p><p><span>§</span><span/><span>使老鼠寿命更长的</span><span>95</span><span>件事</span></p><p><span>§</span><span/><span>诊所里有</span><span>70</span><span>种可能会使人寿命更长的药物</span></p><p><span>介绍</span></p><p><span>随着年龄的增长，死亡的机会会增加。</span></p><p><span/></p><p><span/></p><p><span/></p><p><span>随着年龄的增长，死于某些疾病的机会也会增加。</span><span/></p><p><span/></p><p><span>为什么会这样？</span><span/></p><p><span/></p><p><span>一个简单的解释就是，就像一辆旧车一样，您会随机累积损坏。</span><span/></p><p><span/></p><p><span>但是，我们可以做许多简单的事情来使动物的寿命更长。为什么？我们真的不知道。</span></p><p><span/></p><p><span>少吃可使小鼠寿命更长。</span></p><p><span/></p><p><span/></p><p><span/></p><p><span>一些基因突变后可使小鼠寿命更长，</span></p><p><span/></p><p><span/></p><p><span>批准用于人类的几种药物也可使小鼠寿命更长。</span></p><p><span/></p><p><span>还有其他</span><span>-</span><span>我们将在下面介绍。</span><span/></p><p><span/></p><p><span>那么，如何研究衰老呢？</span></p><p><span/></p><p><span>我将其归纳为以下内容：试图弄清楚随着年龄的增长会累积什么样的损害，如何逆转这种累积，并寻找我们可以翻转人类生物学以延长寿命的开关。</span></p><p><span/></p><p><span/></p><p><span>长寿研究领域</span></p><p><span>热量限制</span></p><p><span/></p><p><span>概览：减少饮食，可以通过多种方式使您的寿命更长</span><span>-</span><span>但是，您的身体只是利用卡路里的数量作为信号吗？</span></p><p><span/></p><p><span>在</span><span>1930</span><span>年代，研究人员想做一个实验，看大萧条期间增长速度缓慢是否会影响寿命。他们通过给老鼠喂食比平时少吃的食物对老鼠进行了测试。令他们惊讶的是，这实际上</span><span>使老鼠的寿命更长</span><span>！这是一个开创性的发现。我们第一次改变了动物的环境，使其寿命比正常情况下更长。</span><span/></p><p><span/></p><p><span>从那时起，研究人员一直试图发现其工作原理。影响取决于您拥有的基因，正在吃的食物以及少吃的食物。如果您将许多遗传上不同的小鼠品系用于同一饮食（将卡路里减少约</span><span>40</span><span>％），则有时</span><span>不到</span><span>1/5</span><span>的小鼠品系寿命更长</span><span>。饮食组成也起作用。仅</span><span>降低蛋白质</span><span>或</span><span>特定氨基酸</span><span>，同时保持总卡路里摄入量不变，就可以延长小鼠的寿命。用</span><span>生酮饮食</span><span>喂养小鼠似乎也有帮助。过多减少食物摄入量将导致饥饿，因此，根据情况选择合适的饮食。</span></p><p><span/></p><p><span>尽管长期的人类研究稀少，但研究人员在猴子身上进行了两次热量限制实验，其中一项显示</span><span>了提高存活率的有希望的结果</span><span>。为避免连续节食的困难，每天禁食</span><span>〜</span><span>8 +</span><span>小时或每月</span><span>5</span><span>天，或以各种不同的周期禁食也可能会有帮助。这称为</span><span>间歇禁食</span><span>。在医学上，间歇性禁食可能有助于化疗期间的恢复。一些与寿命有关的途径涉及氨基</span><span>酸水平的检测，因此特定的生物过程而不是总卡路里摄入量可以控制寿命的延长。</span></p><p><span/></p><p><span>胰岛素</span><span>/ IGF</span></p><p><span/></p><p><span>概览：与生长和胰岛素信号传导相关的遗传途径与衰老相关</span></p><p><span/></p><p><span>在</span><span>1983-1993</span><span>年发表的论文中，研究人员介绍了一种基因可以控制寿命的概念。当这个领域的一位创始人辛西娅</span><span>·</span><span>凯尼恩（</span><span>Cynthia Kenyon</span><span>）同意让我作为</span><span>12</span><span>岁的孩子在她的实验室工作时，我就开始了科学工作。我将永远感激她的友善和指导。以前我们知道热量的限制会使动物的寿命更长，但是</span><span>Kenyon</span><span>和其他科学家（包括</span><span>Michael Klass</span><span>，</span><span/><span>David Friedman</span><span>和</span><span>Tom Johnson</span><span>）</span><span>发现了可使蠕虫寿命更长的突变基因。</span><span>Kenyon</span><span>发现的基因编码的蛋白质类似于人体内的胰岛素样生长因子和胰岛素受体。在小鼠中，</span><span>这两个途径的</span><span>突变成员</span><span>都</span><span>可以</span><span>延长寿命</span><span>。我们今天拥有的寿命最长的小鼠突变体之一是</span><span>矮小鼠</span><span>。在一项研究中，具有类似矮人突变的人似乎比未突变的亲人</span><span>罹患与年龄有关的疾病更少</span><span>。</span></p><p><span/></p><p><span>我着迷的事实是，许多针对糖尿病而开发的药物，未考虑将其用于其他地方，后来却证明与衰老有关。</span><span>二甲双胍</span><span>和</span><span>FGF-21</span><span>就是很好的例子。二甲双胍是用于治疗</span><span>2</span><span>型糖尿病的小分子，而</span><span>FGF-21</span><span>是血液中的一种蛋白质，可以延长小鼠的寿命。我们仍在弄清楚</span><span>胰岛素</span><span>/ IGF</span><span>途径是如何起作用的，特别是哪种分子可能正在驱动我们观察到的寿命效应。</span><span/></p><p><span/></p><p><span>共生</span></p><p><span/></p><p><span>乍一看：年轻的血液使老年小鼠更健康，但是为什么呢？</span></p><p><span/></p><p><span>德古拉想喝年轻的血液，但是那与衰老有什么关系呢？</span><span>上世纪</span><span>70</span><span>年代发表</span><span>的</span><span>一篇论文</span><span>表明，将成年雌性和雌性小鼠连接在一起，使它们共享血液，可以延长寿命。几十年后的</span><span>2005</span><span>年，斯坦福大学的科学家证明了这种方法可能有助于</span><span>老的肌肉干细胞修复伤口</span><span>。然后，在</span><span>2011</span><span>年，一系列论文表明这种方法以及其他类似方法（例如向</span><span>年老的老鼠</span><span>注射</span><span>幼血</span><span>）使老鼠更容易</span><span>记忆事物</span><span>，并随着年龄的增长而改善</span><span>心脏</span><span>和</span><span>肌肉的功能</span><span>。这些发现增加了对该领域的兴奋和兴趣，并引发了一波创业公司。</span><span/></p><p><span/></p><p><span>该领域的研究人员已经提出了造成这种现象的许多可能原因。清洁幼鼠血液的幼鼠中的蛋白质，小囊泡或细胞都可能是这种作用的一部分。许多公司正试图弄清是否涉及特殊蛋白质或分子。要解决的主要问题是，我们是否可以分离出一些导致共生效应的关键因素，以及与寿命有关的表型将转化成多少以改善人类健康。</span></p><p><span/></p><p><span>衰老</span></p><p><span/></p><p><span>乍一看：您的细胞中有一部分比其他细胞更老，因此我们希望消除它们</span></p><p><span/></p><p><span>随着年龄的增长，细胞也会变老。但是您的某些细胞变老的方式要比其他细胞差得多。您可能听说过一种叫做端粒酶的东西。如果您没有记错的话，那是可以使</span><span>DNA</span><span>末端保持足够长的时间，从而使您的细胞仍然可以分裂的东西。当您的一个细胞用尽端粒酶时，它无法复制更多的自身。如果细胞粘在周围，即使停止工作也拒绝死亡，并开始向免疫系统分泌信号，我们称其为</span><span>“</span><span>衰老细胞</span><span>”</span><span>。</span></p><p><span/></p><p><span>当您摆脱这些细胞会怎样？一些</span><span>年龄</span><span>比正常人</span><span>快的动物</span><span>具有大量的</span><span>“</span><span>衰老细胞</span><span>”</span><span>，并且是很好的实验模型。</span><span>2011</span><span>年，来自</span><span>Mayo</span><span>诊所的一组研究人员清除了其中一种动物模型中的许多衰老细胞，发现所产生的</span><span>小鼠老年时更健康</span><span>（此外，它们没有白内障和弯曲的脊椎，通常在晚年出现）。在</span><span>2016</span><span>年，同</span><span>一位</span><span>研究人员发现，摆脱正常小鼠中的衰老细胞</span><span>可以延长它们的健康寿命</span><span>。剔除衰老细胞是棘手的，因为它们没有很多唯一的标识符。公司正在努力寻找凭经验找到杀死衰老细胞的东西，或者找出破坏它们的具体机制。</span></p><p><span/></p><p><span>自噬</span></p><p><span/></p><p><span>乍一看：牢房的垃圾处理单元会随着年龄的增长而恶化，改善它可能会延长健康寿命</span></p><p><span/></p><p><span>从分子水平上讲，您的身体会产生大量垃圾，细胞需要清除这些垃圾。仅增加一种有助于清除垃圾的蛋白质的表达就足以使</span><span>小鼠的寿命延长约</span><span>17</span><span>％</span><span>。细胞将旧的蛋白质和其他分子回收到称为溶酶体的大囊泡中。它包含许多蛋白质，其作用是将吞噬的旧细胞部分切碎。在溶酶体中起作用的蛋白质的基因在</span><span>帕金森氏</span><span>病等疾病中发生了突变。因此，改善这一过程与神经退行性疾病有直接关系。随着溶酶体的变老，其中会堆积更多的垃圾，使其无法降解。寻找制造更多溶酶体或帮助溶酶体降解垃圾的方法可能是有趣的治疗途径。</span><span/></p><p><span/></p><p><span>下丘脑</span></p><p><span/></p><p><span>一目了然：仅在大脑组织中发生变化时，数量惊人的事物可以延长寿命</span></p><p><span/></p><p><span>仅改变大脑中的某些东西就足以使鼠标寿命更长。例如，如果下丘脑认为温度过高，则会降低小鼠的核心体温，</span><span>从而导致寿命略长</span><span>。</span><span>更改级别</span><span>的</span><span>多种</span><span>的</span><span>基因</span><span>在</span><span>大脑特定的方式</span><span>也可以</span><span>使鼠标寿命更长</span><span>我们知道下丘脑会产生一种叫做生长激素释放激素（</span><span>GHRH</span><span>）的物质，它负责释放生长激素。生长激素似乎与寿命密切相关，因此下丘脑可能是重要的控制点。一个有趣的问题是，仅通过改变大脑，您就能在多大程度上影响整个生物体的寿命。</span></p><p><span/></p><p><span>生殖系统</span></p><p><span/></p><p><span>一目了然：消除繁殖能力可以延长寿命</span></p><p><span/></p><p><span>10</span><span>年前，我从事的第一个项目是试图了解有关蠕虫繁殖的怪异事实。如果您吃些小蠕虫并摆脱它们的性腺（我知道，这很奇怪），它们的</span><span>寿命比正常人长</span><span>60</span><span>％</span><span>。但这仅在您清除内部物质（精子</span><span>/</span><span>卵子</span><span>-</span><span>这些蠕虫是雌雄同体的虫，这意味着它们既携带又携带）时才起作用。如果您摆脱了</span><span>所有问题，寿命就会恢复正常</span><span>。</span></p><p><span/></p><p><span>这不仅限于蠕虫。根据韩国太监的法庭记录，这些太监的</span><span>寿命</span><span>往往</span><span>比其同龄人长</span><span>14-19</span><span>岁</span><span>。有些人试图做一些事情，例如将年轻的卵巢移植到老年小鼠中，看是否有帮助（</span><span>这可能会增加寿命</span><span>）。也有许多报告显示，当您延长寿命时，生育能力下降。可能需要权衡取舍（生育力夺走了可用于其他用途的资源），或者是生殖系统发出的信号，如果衰老受到破坏，它会试图阻止衰老。</span></p><p><span/></p><p><span>线粒体</span></p><p><span/></p><p><span>乍一看：线粒体突变以与直觉相反的方式影响寿命</span></p><p><span/></p><p><span>您可能已经听说过线粒体，称为细胞的</span><span>“</span><span>动力源</span><span>”</span><span>。有趣的是，它们确实像大坝一样发电。</span><span>-</span><span>它们以一种方式泵送质子（带正电的粒子），然后向回滑动时使用它们以运行一种马达，该马达产生的小能量分子被细胞中的许多实体所使用。人们谈论线粒体时会想到的一个概念是</span><span>“</span><span>氧化应激</span><span>”</span><span>，即如果分子具有很高的反应性（例</span><span>如，它们具有氧气，吸收了一些额外的电子，并且现在想要将其释放到其他分子上），那么它们很可能会干扰细胞中的许多其他分子，这些分子应该留给自己的设备使用。</span></p><p><span/></p><p><span>奇怪的是，随着时间的流逝，这个故事开始改变。的确，泵送充满活性氧的动物是不好的，并且可以通过</span><span>增加</span><span>应该清除线粒体</span><span>的</span><span>蛋白质</span><span>的水平</span><span>来</span><span>延长</span><span>小鼠的</span><span>寿命</span><span>。但是，您也可以变异本应有助于线粒体的物质，</span><span>从而延长寿命</span><span>！这是违反直觉的，并且一个假设是一点点压力是好的，因为它会迫使您的细胞增强防御能力并增加使活性氧中和的分子的中性。但是我们真的不知道。</span><span/></p><p><span/></p><p><span>西尔图因斯</span></p><p><span/></p><p><span>一目了然：瑟土因蛋白可以改变</span><span>DNA</span><span>并延长寿命</span></p><p><span/></p><p><span>Sirtuins</span><span>在</span><span>DNA</span><span>包裹的结构蛋白球上添加标签。听起来很奇怪，但请考虑一下将纱线缠绕在纸板管上。当他们在</span><span>DNA</span><span>毛线球上添加标签时，它会改变</span><span>DNA</span><span>的折叠和表达方式。因此，他们的行动之一就是控制基因的作用。</span></p><p><span/></p><p><span>Sirtuins</span><span>被首次发现可以</span><span>延长酵母的寿命</span><span>，而且在</span><span>蠕虫</span><span>，</span><span>苍蝇</span><span>和</span><span>小鼠中</span><span>似乎也能</span><span>延长寿命</span><span>。他们依靠</span><span>NAD</span><span>来完成工作，因此，当您看到人们在谈论</span><span>NR</span><span>或</span><span>NAD</span><span>的其他前体时，您可以将其视为也可以帮助</span><span>sirtuins</span><span>完成他们的工作。您可以在老年时给它们</span><span>NR</span><span>来</span><span>延长它们的寿命</span><span>。</span><span/></p><p><span/></p><p><span>[</span><span>目前仅此部分</span><span>-</span><span>我计划在时间允许的情况下添加到上面。还有更多要谈论的！</span><span>]</span></p><p><span/></p><p><span>寿命数据</span></p><p><span>为了给该领域提供一些背景信息，我认为进行更全面的调查会很有趣。下面实际上是我们已经看到的可以改善鼠标寿命的所有事物，按引用次数</span><span>/</span><span>年列出。</span><span/></p><p><span/></p><p><span>我认为列表底部的某些论文实际上很酷，并且可能会简短地提及。</span></p><p><span/></p><p><span>（方法</span><span>-</span><span>我拍摄了所有具有证明的鼠标寿命效果的论文，提取了关键寿命图，并且在文本未列出实际中位数或其他寿命的情况下，使用虚拟像素标尺将像素计数到中位数。相应地允许一些标准偏差！）。</span></p><p><span>介入</span></p><p><span>平均寿命增加（治疗</span><span>/</span><span>控制）</span></p><p><span>出版年份</span></p><p><span>笔记</span></p><p><span>参考</span></p><p><span>去除衰老细胞</span></p><p><span>135</span><span>％</span></p><p><span>2016</span><span>年</span></p><p><span>不影响轮转性能，不歧视物体。伤口闭合稍延迟。</span></p><p><span>1</span><span>个</span></p><p><span>雷帕霉素</span></p><p><span>110</span><span>％</span></p><p><span>2009</span><span>年</span></p><p><span>rapapyicn</span><span>的后期治疗延长了寿命（来自多站点</span><span>NIA</span><span>研究的女性成年）</span></p><p><span>2</span></p><p><span>NR</span></p><p><span>105</span><span>％</span></p><p><span>2016</span><span>年</span></p><p><span>要求增加跑步距离</span></p><p><span>3</span></p><p><span>过氧化氢酶</span></p><p><span>117</span><span>％</span></p><p><span>2005</span><span>年</span></p><p><span>与对照相比，线粒体靶向的过氧化氢酶表达可延长小鼠的寿命</span></p><p><span>4</span></p><p><span>Sirt6</span><span>过表达</span></p><p><span>115</span><span>％</span></p><p><span>2012</span><span>年</span></p><p><span>Sirt6</span><span>过表达可延长雄性小鼠的寿命</span></p><p><span>5</span></p><p><span>二甲双胍</span></p><p><span>106</span><span>％</span></p><p><span>2013</span><span>年</span></p><p><span>在男性中，二甲双胍应用后寿命小而显着延长</span></p><p><span>6</span></p><p><span>DN-IκBα</span></p><p><span>110</span><span>％</span></p><p><span>2013</span><span>年</span></p><p><span>负值下调</span><span>IKK-beta</span><span>活性，显着下调至中年小鼠的下丘脑</span></p><p><span>7</span></p><p><span>克洛托</span></p><p><span>120</span><span>％</span></p><p><span>2005</span><span>年</span></p><p><span>在人类延伸因子</span><span>1α</span><span>启动子下过表达可延长寿命，并降低生育力</span></p><p><span>8</span></p><p><span>S6K1</span></p><p><span>118</span><span>％</span></p><p><span>2009</span><span>年</span></p><p><span>与野生型小鼠相比，</span><span>S6K1</span><span>的</span><span>KO</span><span>延长寿命</span></p><p><span>9</span></p><p><span>66</span></p><p><span>128</span><span>％</span></p><p><span>1999</span><span>年</span></p><p><span>p66shc</span><span>（原癌基因基因座</span><span>SHC</span><span>的成员）的突变可延长寿命。可能只是由于癌症作用。</span></p><p><span>10</span></p><p><span>降低蛋白质：碳水化合物比例</span></p><p><span>128</span><span>％</span></p><p><span>2014</span><span>年</span></p><p><span>各种蛋白质，碳水化合物和总能量水平。</span></p><p><span>11</span></p><p><span>脂肪特异性胰岛素受体敲除小鼠</span></p><p><span>111</span><span>％</span></p><p><span>2003</span><span>年</span></p><p><span>脂肪特异性胰岛素受体敲除小鼠的寿命显着增加</span></p><p><span>12</span></p><p><span>NZB / OlaHsd</span><span>线粒体突变的</span><span>C57BL / 6</span><span>小鼠</span></p><p><span>120</span><span>％</span></p><p><span>2016</span><span>年</span></p><p><span>相同的核，不同的线粒体</span><span>DNA</span><span>。</span></p><p><span>13</span></p><p><span>空腹模仿饮食</span></p><p><span>112</span><span>％</span></p><p><span>2015</span><span>年</span></p><p><span>口蹄疫，然后正常</span><span>10</span><span>天，然后重复</span></p><p><span>14</span></p><p><span>雷帕霉素</span></p><p><span>127</span><span>％</span></p><p><span>2014</span><span>年</span></p><p><span>雷帕霉素从</span><span>9</span><span>个月大开始，在最大剂量下体重下降</span><span>〜</span><span>30</span><span>％</span></p><p><span>15</span></p><p><span>脑特异性</span><span>Sirt1</span><span>表达</span></p><p><span>116</span><span>％</span></p><p><span>2013</span><span>年</span></p><p><span>雌性小鼠脑特异性</span><span>Sirt1</span><span>表达增加了野生型的寿命</span></p><p><span>16</span></p><p><span>SRT1720</span></p><p><span>104</span><span>％</span></p><p><span>2014</span><span>年</span></p><p><span>在</span><span>28</span><span>周龄时开始饮食，寿命增长很小</span></p><p><span>17</span></p><p><span>亚精胺</span></p><p><span>111</span><span>％</span></p><p><span>2016</span><span>年</span></p><p><span>多胺，在饮用水中使用</span></p><p><span>18</span><span>岁</span></p><p><span>Atg5</span><span>过表达</span></p><p><span>117</span><span>％</span></p><p><span>2013</span><span>年</span></p><p><span>普遍表达</span><span>Atg5</span><span>（对自噬体确认至关重要）的转基因小鼠寿命更长。</span></p><p><span>19</span></p><p><span>端粒酶</span></p><p><span>124</span><span>％</span></p><p><span>2012</span><span>年</span></p><p><span>显示端粒酶疗法可延长寿命的论文</span></p><p><span>20</span></p><p><span>胰岛素受体底物无效</span></p><p><span>132</span><span>％</span></p><p><span>2008</span><span>年</span></p><p><span>胰岛素受体底物</span><span>1</span><span>延长雌性小鼠的寿命</span></p><p><span>21</span></p><p><span>斯内尔</span><span>·</span><span>矮鼠</span></p><p><span>142</span><span>％</span></p><p><span>2001</span></p><p><span>斯内尔侏儒老鼠纸显示寿命延长</span></p><p><span>22</span></p><p><span>艾姆斯矮小鼠</span></p><p><span>168</span><span>％</span></p><p><span>1996</span><span>年</span></p><p><span>原始的</span><span>Ames</span><span>矮人鼠标纸显示寿命延长</span></p><p><span>23</span></p><p><span>s-Arf / p53</span></p><p><span>113</span><span>％</span></p><p><span>2007</span><span>年</span></p><p><span>p53</span><span>和上游调节剂</span><span>Arf / p16Ink4a</span><span>的额外副本可延长使用寿命</span></p><p><span>24</span></p><p><span>哺乳期生长缓慢</span></p><p><span>106</span><span>％</span></p><p><span>2004</span><span>年</span></p><p><span>用低蛋白饮食喂养的被水坝哺乳的雄性小鼠的寿命长于其对照组。</span></p><p><span>25</span></p><p><span>蛋氨酸限制</span></p><p><span>111</span><span>％</span></p><p><span>2005</span><span>年</span></p><p><span>蛋氨酸的限制增加了小鼠的寿命，此处存活至少</span><span>1</span><span>年的小鼠的中位寿命增加。</span></p><p><span>26</span></p><p><span>雷帕霉素（</span><span>3</span><span>个月）</span></p><p><span>114</span><span>％</span></p><p><span>2016</span><span>年</span></p><p><span>从治疗时间算起的寿命为</span><span>23-24</span><span>个月，使用</span><span>24</span><span>个月来获得百分比，所以这是一个估计值</span></p><p><span>27</span></p><p><span>GHR</span><span>血压</span></p><p><span>138</span><span>％</span></p><p><span>2000</span></p><p><span>缺乏生长激素受体</span><span>/</span><span>结合蛋白的小鼠的寿命更长（此处显示的是女性平均数，不是中位数，寿命）</span></p><p><span>28</span></p><p><span>mTOR</span></p><p><span>116</span><span>％</span></p><p><span>2013</span><span>年</span></p><p><span>mTOR</span><span>耗尽可延长使用寿命</span></p><p><span>29</span></p><p><span>PTEN</span><span>过表达</span></p><p><span>112</span><span>％</span></p><p><span>2012</span><span>年</span></p><p><span>PTEN</span><span>（一种抗</span><span>PI3K</span><span>的肿瘤抑制因子）的过表达延长了小鼠的寿命</span></p><p><span>30</span></p><p><span>Myc</span><span>（</span><span>+/-</span><span>）</span></p><p><span>121</span><span>％</span></p><p><span>2015</span><span>年</span></p><p><span>声称体重和寿命之间没有关联</span></p><p><span>31</span></p><p><span>FGF-21</span></p><p><span>139</span><span>％</span></p><p><span>2012</span><span>年</span></p><p><span>FGF-21</span><span>的肝特异性表达（抑制生长激素并减少</span><span>IGF</span><span>的产生）可延长寿命，此处显示的是女性寿命</span></p><p><span>32</span></p><p><span>BubR1</span><span>过表达</span></p><p><span>114</span><span>％</span></p><p><span>2012</span><span>年</span></p><p><span>激酶定位于线粒体，过表达可延长寿命</span></p><p><span>33</span></p><p><span>AC5 KO</span></p><p><span>132</span><span>％</span></p><p><span>2007</span><span>年</span></p><p><span>AC5</span><span>基因敲除小鼠的寿命比对照组长，可能与对</span><span>cAMP</span><span>产生和</span><span>β-</span><span>肾上腺素受体信号传导的影响有关。</span></p><p><span>34</span></p><p><span>17-α-</span><span>雌二醇</span></p><p><span>112</span><span>％</span></p><p><span>2013</span><span>年</span></p><p><span>17-α-</span><span>雌二醇可延长男性寿命，但不延长女性寿命（如预期）</span></p><p><span>35</span></p><p><span>阿卡波糖</span></p><p><span>122</span><span>％</span></p><p><span>2013</span><span>年</span></p><p><span>阿卡波糖延长男性寿命，延长女性寿命</span></p><p><span>36</span></p><p><span>TRPV1-/-</span></p><p><span>114</span><span>％</span></p><p><span>2014</span><span>年</span></p><p><span>静态交换率在</span><span>16 mo</span><span>到</span><span>3 mo</span><span>相似</span></p><p><span>37</span></p><p><span>SRT2104</span></p><p><span>106</span><span>％</span></p><p><span>2014</span><span>年</span></p><p><span>从</span><span>28</span><span>周龄开始饮食，如果有的话，增加很少</span></p><p><span>38</span></p><p><span>Hcrt-UCP2</span></p><p><span>128</span><span>％</span></p><p><span>2006</span><span>年</span></p><p><span>降钙素启动子下的</span><span>UCP2</span><span>降低核心体温，延长寿命</span></p><p><span>39</span></p><p><span>G6PD</span><span>过度表达</span></p><p><span>114</span><span>％</span></p><p><span>2016</span><span>年</span></p><p><span>降低</span><span>NADP +</span></p><p><span>40</span></p><p><span>IGF-1</span><span>受体脑</span><span>KO</span><span>（</span><span>+/-</span><span>）</span></p><p><span>109</span><span>％</span></p><p><span>2008</span><span>年</span></p><p><span>脑特异性</span><span>IGF-1</span><span>受体</span><span>+/-</span><span>小鼠比野生型小鼠寿命更长</span></p><p><span>41</span></p><p><span>SURF-1 KO</span></p><p><span>121</span><span>％</span></p><p><span>2007</span><span>年</span></p><p><span>SURF1</span><span>（一种细胞色素</span><span>C</span><span>氧化酶装配因子）中的突变可延长寿命。线粒体。</span></p><p><span>42</span></p><p><span>垃圾放大网（</span><span>CR</span><span>）</span></p><p><span>118</span><span>％</span></p><p><span>2009</span><span>年</span></p><p><span>前</span><span>20</span><span>天垫料增加</span><span>50</span><span>％，以限制热量</span></p><p><span>43</span></p><p><span>mclk-1</span><span>杂合的</span></p><p><span>115</span><span>％</span></p><p><span>2005</span><span>年</span></p><p><span>与野生型相比，</span><span>mclk1</span><span>的杂合敲除（在线粒体呼吸中很重要）可延长小鼠的寿命</span></p><p><span>44</span></p><p><span>去甲双氢愈创木酸</span></p><p><span>112</span><span>％</span></p><p><span>2008</span><span>年</span></p><p><span>NDGA</span><span>和阿司匹林可延长使用寿命。小分子。</span></p><p><span>45</span></p><p><span>阿司匹林</span></p><p><span>108</span><span>％</span></p><p><span>2008</span><span>年</span></p><p><span>NDGA</span><span>和阿司匹林可延长使用寿命。小分子。</span></p><p><span>46</span></p><p><span>SOD</span><span>模拟羧基富勒烯</span></p><p><span>115</span><span>％</span></p><p><span>2008</span><span>年</span></p><p><span>与野生型对照相比，被称为</span><span>SOD</span><span>模拟物的羧基富勒烯可延长治疗小鼠的寿命</span></p><p><span>47</span></p><p><span>去除内脏脂肪组织</span></p><p><span>108</span><span>％</span></p><p><span>2008</span><span>年</span></p><p><span>去除内脏脂肪组织可延长使用寿命</span></p><p><span>48</span></p><p><span>低糖毒素饮食</span></p><p><span>112</span><span>％</span></p><p><span>2007</span><span>年</span></p><p><span>低糖毒素（</span><span>AGEs</span><span>水平低）可延长寿命</span></p><p><span>49</span></p><p><span>Per2</span><span>（</span><span>-/-</span><span>）</span></p><p><span>118</span><span>％</span></p><p><span>2016</span><span>年</span></p><p><span>寿命研究不完整</span></p><p><span>50</span></p><p><span>新生儿二甲双胍</span></p><p><span>120</span><span>％</span></p><p><span>2015</span><span>年</span></p><p><span>出生后第</span><span>3</span><span>、</span><span>5</span><span>、</span><span>7</span><span>天收到动物</span><span>-</span><span>对雌性不利，对雄性有利。</span></p><p><span>51</span></p><p><span>GHRH KO</span></p><p><span>146</span><span>％</span></p><p><span>2013</span><span>年</span></p><p><span>GHRH</span><span>（生长激素释放激素）破坏可延长寿命，大概是通过胰岛素</span><span>/ IGF</span><span>途径轴</span></p><p><span>52</span></p><p><span>Sod-2</span><span>过度表达</span></p><p><span>104</span><span>％</span></p><p><span>2007</span><span>年</span></p><p><span>相对于野生型，针对线粒体的</span><span>SOD-2</span><span>的过表达增加了小鼠的寿命</span></p><p><span>53</span></p><p><span>金属硫蛋白心脏特异性表达</span></p><p><span>114</span><span>％</span></p><p><span>2006</span><span>年</span></p><p><span>与</span><span>WT FVB</span><span>对照相比，抗氧化剂金属硫蛋白的心脏特异性表达延长了野生型小鼠的寿命。</span></p><p><span>54</span></p><p><span>IGF1R</span><span>（</span><span>+/-</span><span>）</span></p><p><span>121</span><span>％</span></p><p><span>2013</span><span>年</span></p><p><span>IGF1 / 2</span><span>激活酪氨酸激酶受体</span></p><p><span>55</span></p><p><span>Ink4a / Arf / Ink4b</span></p><p><span>116</span><span>％</span></p><p><span>2009</span><span>年</span></p><p><span>编码</span><span>2</span><span>个</span><span>CDK</span><span>（</span><span>p16</span><span>和</span><span>p15</span><span>）和</span><span>Arf</span><span>（</span><span>p53</span><span>的上游）</span></p><p><span>56</span></p><p><span>成人发病率（</span><span>-/-</span><span>）</span></p><p><span>100</span><span>％</span></p><p><span>2016</span><span>年</span></p><p><span>雄性小鼠的胰岛素比雌性小鼠高</span><span>> 2</span><span>倍</span></p><p><span>57</span></p><p><span>卵巢移植</span></p><p><span>117</span><span>％</span></p><p><span>2003</span><span>年</span></p><p><span>原始文件显示，将年轻的卵巢移植到老年动物中可以延长寿命</span></p><p><span>58</span></p><p><span>UCP-1</span><span>转基因</span></p><p><span>111</span><span>％</span></p><p><span>2007</span><span>年</span></p><p><span>具有骨骼肌特异性</span><span>UCP1</span><span>的转基因小鼠的寿命延长。如果有少量增加。</span></p><p><span>59</span></p><p><span>帕普</span></p><p><span>131</span><span>％</span></p><p><span>2010</span><span>年</span></p><p><span>PAPP-A</span><span>的敲除（通过降解抑制性</span><span>IGF</span><span>结合蛋白增强</span><span>IGF-1</span><span>活性）延长了野生型的寿命，女性寿命如图所示</span></p><p><span>60</span></p><p><span>猪油</span><span>CR</span><span>饮食</span></p><p><span>132</span><span>％</span></p><p><span>2015</span><span>年</span></p><p><span>从</span><span>4</span><span>个月开始减少</span><span>40</span><span>％</span></p><p><span>61</span></p><p><span>Riib</span><span>（</span><span>PKA</span><span>亚基）功能丧失</span></p><p><span>114</span><span>％</span></p><p><span>2009</span><span>年</span></p><p><span>与野生型相比，</span><span>PKA</span><span>的一个亚基</span><span>RIIbeta</span><span>的敲除增加了小鼠的寿命</span></p><p><span>62</span></p><p><span>肌生长抑制素（</span><span>+/-</span><span>）</span></p><p><span>109</span><span>％</span></p><p><span>2015</span><span>年</span></p><p><span>敲除诱导双肌小鼠</span></p><p><span>63</span></p><p><span>Akt1 +/-</span></p><p><span>113</span><span>％</span></p><p><span>2013</span><span>年</span></p><p><span>相对于野生型，</span><span>Akt1</span><span>的单倍剂量不足会增加小鼠的寿命。胰岛素</span><span>/ IGF-1</span><span>途径。</span></p><p><span>64</span></p><p><span>miR-17</span></p><p><span>117</span><span>％</span></p><p><span>2014</span><span>年</span></p><p><span>尚不清楚</span><span>miR-17</span><span>是否具有主要功能</span></p><p><span>65</span></p><p><span>NDGA</span></p><p><span>111</span><span>％</span></p><p><span>2015</span><span>年</span></p><p><span>占叶子干重的约</span><span>12.5</span><span>％</span></p><p><span>66</span></p><p><span>FAT10ko</span></p><p><span>119</span><span>％</span></p><p><span>2014</span><span>年</span></p><p><span>泛素样蛋白质，可以指示蛋白质进入蛋白酶体。</span></p><p><span>67</span></p><p><span>鼻内</span><span>Hsp70</span></p><p><span>116</span><span>％</span></p><p><span>2015</span><span>年</span></p><p><span>从</span><span>17</span><span>个月开始，似乎可以延长使用寿命</span></p><p><span>68</span></p><p><span>RasGRF1</span><span>（</span><span>-/-</span><span>）</span></p><p><span>120</span><span>％</span></p><p><span>2011</span><span>年</span></p><p><span>Ras-</span><span>鸟嘌呤核苷酸交换因子（</span><span>Ras-GRF1</span><span>）</span><span>-/-</span><span>小鼠相比野生型具有更长的寿命。</span></p><p><span>69</span></p><p><span>Lmna-Lcs</span><span>（仅</span><span>Lamin C</span><span>）</span></p><p><span>113</span><span>％</span></p><p><span>2014</span><span>年</span></p><p><span>仅表达</span><span>Lamin-C</span><span>的小鼠的体重和肿瘤发生率增加</span></p><p><span>70</span></p><p><span>Cisd2</span><span>过表达</span></p><p><span>119</span><span>％</span></p><p><span>2011</span><span>年</span></p><p><span>Cisd2</span><span>转基因小鼠（表达更多）的寿命比野生型更长。</span><span>Cisd2</span><span>是在线粒体外膜上表达的跨膜蛋白，与人类长寿所在地有关。</span></p><p><span>71</span></p><p><span>美托洛尔</span></p><p><span>110</span><span>％</span></p><p><span>2013</span><span>年</span></p><p><span>与野生型小鼠相比，给小鼠服用</span><span>β-</span><span>肾上腺素受体阻滞剂美托洛尔可延长寿命</span></p><p><span>72</span></p><p><span>奈比洛尔</span></p><p><span>106</span><span>％</span></p><p><span>2013</span><span>年</span></p><p><span>与野生型小鼠相比，给小鼠服用</span><span>β-</span><span>肾上腺素受体阻滞剂奈必洛尔可延长寿命</span></p><p><span>73</span></p><p><span>uPA</span><span>（在晶状体</span><span>/ CNS</span><span>神经细胞中）</span></p><p><span>118</span><span>％</span></p><p><span>1997</span><span>年</span></p><p><span>在</span><span>α-</span><span>晶状体蛋白启动子下的</span><span>uPA</span><span>表达可延长寿命，小</span><span>/</span><span>少吃</span></p><p><span>74</span></p><p><span>MIF-1 KO</span></p><p><span>116</span><span>％</span></p><p><span>2010</span><span>年</span></p><p><span>MIF-1</span><span>敲除突变体（</span><span>T</span><span>细胞衍生的细胞因子）延长寿命</span></p><p><span>75</span></p><p><span>mGsta4-</span><span>无效</span></p><p><span>113</span><span>％</span></p><p><span>2009</span><span>年</span></p><p><span>酶可防止脂质过氧化，奇怪的是它的活性较少可能会延长寿命</span></p><p><span>76</span></p><p><span>肌肉特异性</span><span>GHRKO</span></p><p><span>109</span><span>％</span></p><p><span>2015</span><span>年</span></p><p><span>肌酐激酶启动子敲除</span></p><p><span>77</span></p><p><span>CAM-α</span><span>（</span><span>1A</span><span>）</span><span>AR</span><span>小鼠</span></p><p><span>110</span><span>％</span></p><p><span>2011</span><span>年</span></p><p><span>具有</span><span>α1-</span><span>肾上腺素能受体（</span><span>CAM-alpha1aAR</span><span>）组成型活性突变体形式的小鼠的寿命比野生型对照的小鼠更长</span></p><p><span>78</span></p><p><span>心脏特异性过氧化氢酶过表达</span></p><p><span>113</span><span>％</span></p><p><span>2007</span><span>年</span></p><p><span>过氧化氢酶在小鼠心脏中的过度表达</span></p><p><span>79</span></p><p><span>伊卡林</span></p><p><span>108</span><span>％</span></p><p><span>2015</span><span>年</span></p><p><span>类黄酮</span></p><p><span>80</span></p><p><span>miR-29</span><span>脑特异性</span><span>KO</span></p><p><span>112</span><span>％</span></p><p><span>2016</span><span>年</span></p><p><span>miR-29</span><span>在发育过程中在大脑中高度表达</span></p><p><span>81</span></p><p><span>双母鼠</span></p><p><span>128</span><span>％</span></p><p><span>2010</span><span>年</span></p><p><span>发现准备双胎的小鼠比正常队列寿命更长</span></p><p><span>82</span></p><p><span>RNase-L</span><span>（</span><span>-/-</span><span>）</span></p><p><span>127</span><span>％</span></p><p><span>2007</span><span>年</span></p><p><span>与野生型相比，敲除</span><span>RNase-L</span><span>可以加速小鼠的寿命，表达后可以加速细胞衰老</span></p><p><span>83</span></p><p><span>hMTH1-Tg</span></p><p><span>116</span><span>％</span></p><p><span>2013</span><span>年</span></p><p><span>表达高水平的</span><span>hMTH1</span><span>水解酶，认为可降解</span><span>8-oxodGTP</span><span>和</span><span>8-oxoGTP</span><span>。氧化应激。</span></p><p><span>84</span></p><p><span>DGAT-1-/-</span></p><p><span>126</span><span>％</span></p><p><span>2012</span><span>年</span></p><p><span>敲除</span><span>DGAT1</span><span>可以催化甘油三酸酯的合成，延长小鼠相对于野生型的寿命</span></p><p><span>85</span></p><p><span>IGFBP-2</span><span>过表达</span></p><p><span>105</span><span>％</span></p><p><span>2016</span><span>年</span></p><p><span>蛋白质结合</span><span>IGF1 / 2</span><span>，在怀孕期间降解，性成熟延迟</span></p><p><span>86</span></p><p><span>高脂饮食中的</span><span>PAPP-A</span></p><p><span>105</span><span>％</span></p><p><span>2015</span><span>年</span></p><p><span>选择男性，因此对油库没有不利的发育影响</span></p><p><span>87</span></p><p><span>具有</span><span>clk-1</span><span>转基因的</span><span>clk-1</span><span>（</span><span>-/-</span><span>）</span></p><p><span>128</span><span>％</span></p><p><span>2014</span><span>年</span></p><p><span>clk-1</span><span>在泛醌合成中起作用，但水平并未受到太大影响。</span></p><p><span>88</span></p><p><span>AgRP-/-</span></p><p><span>110</span><span>％</span></p><p><span>2006</span><span>年</span></p><p><span>神经肽是食欲刺激物，过度表达会导致食欲亢进和肥胖。</span></p><p><span>89</span></p><p><span>骨髓移植</span></p><p><span>106</span><span>％</span></p><p><span>2013</span><span>年</span></p><p><span>据称从幼鼠到老鼠进行骨髓移植可延长寿命</span></p><p><span>90</span></p><p><span>年轻的血液注射</span></p><p><span>94</span><span>％</span></p><p><span>2014</span><span>年</span></p><p><span>导致使用寿命缩短</span></p><p><span>91</span></p><p><span>Nas</span><span>（</span><span>-/-</span><span>）小鼠</span></p><p><span>125</span><span>％</span></p><p><span>2011</span><span>年</span></p><p><span>与野生型对照相比，低硫酸盐</span><span>NaS1</span><span>无效小鼠（</span><span>Nas1-/-</span><span>）的寿命增加。</span></p><p><span>92</span></p><p><span>亲环素</span><span>D</span><span>（</span><span>+/-</span><span>）</span></p><p><span>119</span><span>％</span></p><p><span>2017</span><span>年</span></p><p><span>减少最大使用寿命</span></p><p><span>93</span></p><p><span>成人</span><span>PAPP-A</span></p><p><span>120</span><span>％</span></p><p><span>2017</span><span>年</span></p><p><span>他莫昔芬诱导的击倒</span></p><p><span>94</span></p><p><span>Mtbp</span><span>（</span><span>+/-</span><span>）</span></p><p><span>120</span><span>％</span></p><p><span>2016</span><span>年</span></p><p><span>罗塔罗德，开阔地域，血糖，胰岛素，</span><span>IGF-1</span><span>相同。</span></p><p><span>95</span></p><p><span>使老鼠寿命更长的</span><span>95</span><span>件事</span><span>按引文</span><span>/</span><span>年份排序</span></p><p><span>消息来源</span><span>：</span><span>请参阅表</span><span>1</span><span>的参考</span></p><p><span/></p><p><span/></p><p><span>为了娱乐，我拿了清单，将条目与诊所中的药物进行了匹配。下面的部分内容可能已过时（公司有时会花很长时间来更新审判进度），但这是对正在运行的事物数量的有趣的表示，这些事物对寿命的影响非零（可能会猜到）在几乎所有情况下都很小）。方法是相似的</span><span>-</span><span>只是使用</span><span>Clinicaltrials.gov</span><span>来尝试寻找相关的试验和分子，或者通常是使用</span><span>Google</span><span>搜索。</span><span/></p><p><span>长寿班</span></p><p><span>药品</span></p><p><span>相</span></p><p><span>专为</span></p><p><span>开发者</span></p><p><span>参考</span></p><p><span>胰岛素</span><span>/ IGF</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>生长激素受体拮抗剂</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>培维索孟（</span><span>Somavert</span><span>）</span></p><p><span>批准（</span><span>2003</span><span>年</span><span>3</span><span>月）</span></p><p><span>肢端肥大症（</span><span>IGF-1</span><span>水平正常化）</span></p><p><span>辉瑞</span></p><p><span>1</span><span>个</span></p><p><span>Akt1</span><span>拮抗剂</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>Archexin</span><span>（</span><span>Akt1</span><span>反义）</span></p><p><span>阶段</span><span>2</span></p><p><span>胰腺</span><span>/</span><span>肾癌</span></p><p><span>雷克森制药</span></p><p><span>2</span></p><p><span>PAPP-A</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>PAPP-A</span><span>抗体已出版</span></p><p><span>临床前</span></p><p><span>--</span></p><p><span/></p><p><span>3</span></p><p><span>胰岛素受体拮抗剂</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>S961</span><span>和</span><span>S661</span></p><p><span>临床前</span><span>/</span><span>未开发</span></p><p><span>--</span></p><p><span/></p><p><span>4</span></p><p><span>IGF-1</span><span>受体拮抗剂</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>AMG-479</span><span>（</span><span>Ganitumab</span><span>）</span></p><p><span>阶段</span><span>2</span></p><p><span>胰腺癌</span></p><p><span>安进</span></p><p><span>5</span></p><p><span/></p><p><span>AVE1642</span></p><p><span>第二阶段（已终止）</span></p><p><span>肝癌和乳腺癌</span></p><p><span>赛诺菲</span><span>-</span><span>安万特</span><span>/ ImmunoGen</span></p><p><span>6</span></p><p><span/></p><p><span>西妥单抗</span></p><p><span>阶段</span><span>2</span></p><p><span>癌症</span></p><p><span>Lilly / ImClone</span><span>）</span></p><p><span>7</span></p><p><span/></p><p><span>林西替尼</span></p><p><span>阶段</span><span>2</span></p><p><span>卵巢癌</span></p><p><span>OSI</span><span>制药</span><span>/</span><span>阿斯特拉</span></p><p><span>8</span></p><p><span/></p><p><span>AXL-1717</span></p><p><span>阶段</span><span>2</span></p><p><span>癌症</span></p><p><span>Axelar</span><span>）</span></p><p><span>9</span></p><p><span/></p><p><span>菲珠单抗</span></p><p><span>第三阶段（已终止）</span></p><p><span>非小细胞肺癌</span></p><p><span>辉瑞</span></p><p><span>10</span></p><p><span/></p><p><span>PL-225b</span></p><p><span>第</span><span>1</span><span>阶段（已暂停）</span></p><p><span>癌症</span></p><p><span>Piramal Enterprises Ltd /</span><span>默克</span></p><p><span>11</span></p><p><span/></p><p><span>BIIB022</span></p><p><span>第一阶段（已停产）</span></p><p><span>癌症</span></p><p><span>Biogen Idec</span></p><p><span>12</span></p><p><span/></p><p><span>RG1507</span></p><p><span>第二阶段（已停产）</span></p><p><span>癌症</span></p><p><span>Genmab /</span><span>罗氏）</span></p><p><span>13</span></p><p><span/></p><p><span>达洛珠单抗</span></p><p><span>阶段</span><span>2</span></p><p><span>癌症</span></p><p><span>默克</span></p><p><span>14</span></p><p><span/></p><p><span>NT219</span></p><p><span>临床前</span></p><p><span>--</span></p><p><span>TryNovo</span></p><p><span>15</span></p><p><span>GHRH</span><span>拮抗剂</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>JV-1-36</span></p><p><span>临床前</span></p><p><span>--</span></p><p><span/></p><p><span>16</span></p><p><span/></p><p><span>JMR-132</span><span>，</span><span>MZ-5-156</span><span>，</span><span>MIA-601</span><span>，</span><span>MIA-479</span></p><p><span>临床前</span></p><p><span>--</span></p><p><span/></p><p><span>17</span></p><p><span>生长抑素类似物</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>奥曲肽</span></p><p><span>已批准</span></p><p><span>肢端肥大症和某些癌症</span></p><p><span>诺华</span></p><p><span>18</span><span>岁</span></p><p><span/></p><p><span>帕西肽</span></p><p><span>已批准</span></p><p><span>库欣病</span></p><p><span>诺华</span></p><p><span>19</span></p><p><span/></p><p><span>Sandostatin</span></p><p><span>已批准</span></p><p><span>肢端肥大症和某些癌症</span></p><p><span>诺华</span></p><p><span>20</span></p><p><span>热量限制</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>无蛋氨酸饮食</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>蛋氨酸限制饮食</span></p><p><span>阶段</span><span>2</span></p><p><span>代谢综合征</span></p><p><span/></p><p><span>21</span></p><p><span>热量限制方案</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>热量限制</span></p><p><span>--</span></p><p><span>与年龄有关的疾病</span></p><p><span/></p><p><span>22</span></p><p><span>TOR</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>mTORC1</span><span>抑制剂</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>西罗莫司</span></p><p><span>已批准</span></p><p><span>器官移植</span></p><p><span>辉瑞</span></p><p><span>23</span></p><p><span/></p><p><span>替米罗莫司</span></p><p><span>已批准</span></p><p><span>晚期肾细胞癌</span></p><p><span>辉瑞</span></p><p><span>24</span></p><p><span/></p><p><span>依维莫司</span></p><p><span>已批准</span></p><p><span>晚期肾细胞癌，</span><span>SEGA</span><span>与</span><span>TS</span><span>相关</span></p><p><span>诺华</span></p><p><span>25</span></p><p><span/></p><p><span>里达福莫斯</span></p><p><span>拒绝</span><span>NDA</span></p><p><span>转移性软组织或骨肉瘤</span></p><p><span>默克和</span><span>ARIAD</span><span>）</span></p><p><span>26</span></p><p><span>S6K1</span><span>抑制剂</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>PF-4708671</span></p><p><span>临床前</span></p><p><span>--</span></p><p><span/></p><p><span>27</span></p><p><span>西尔图因斯</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>Sirt1</span><span>激动剂</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>SRT2104</span></p><p><span>阶段</span><span>2</span></p><p><span>糖尿病，牛皮癣</span></p><p><span>GSK / Sirtris</span></p><p><span>28</span></p><p><span/></p><p><span>SRT2739</span></p><p><span>阶段</span><span>1</span></p><p><span>内毒素引起的炎症</span></p><p><span>GSK / Sirtris</span></p><p><span>29</span></p><p><span>显示的可用疗法可延长小鼠寿命，而无任何机械假设</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>NDGA</span></p><p><span>阶段</span><span>2</span></p><p><span>前列腺癌</span></p><p><span/></p><p><span>30</span></p><p><span/></p><p><span>阿司匹林（通用）</span></p><p><span>已批准</span></p><p><span>血管适应症，再凝集程序和风湿性疾病适应症</span></p><p><span/></p><p><span>31</span></p><p><span/></p><p><span>二甲双胍（通用）</span></p><p><span>已批准</span></p><p><span>II</span><span>型糖尿病</span></p><p><span/></p><p><span>32</span></p><p><span/></p><p><span>17-α-</span><span>雌二醇（通用）</span></p><p><span>上市</span></p><p><span>脱发</span></p><p><span/></p><p><span/></p><p><span/></p><p><span>阿卡波糖</span></p><p><span>已批准</span></p><p><span>II</span><span>型糖尿病</span></p><p><span/></p><p><span>33</span></p><p><span>端粒</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>TA-65</span></p><p><span>市场补充</span></p><p><span>--</span></p><p><span>山脉科学</span></p><p><span>34</span></p><p><span>NFkB</span><span>抑制剂</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>IKK-β</span><span>抑制剂</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>化合物</span><span>A</span></p><p><span>临床前</span></p><p><span>--</span></p><p><span/></p><p><span>35</span></p><p><span/></p><p><span>化合物</span><span>1</span></p><p><span>临床前</span></p><p><span>--</span></p><p><span/></p><p><span>36</span></p><p><span>NFkB</span><span>抑制剂</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>猫</span><span>1004</span></p><p><span>1/2</span><span>阶段</span></p><p><span>DMD</span></p><p><span>分解病</span></p><p><span>37</span></p><p><span/></p><p><span>发现</span><span>19</span><span>种抑制</span><span>NFkB</span><span>信号传导的药物</span></p><p><span>临床前工作</span></p><p><span>--</span></p><p><span/></p><p><span>38</span></p><p><span>FGF-21</span><span>类似物</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>LY2405319</span></p><p><span>阶段</span><span>1</span></p><p><span>II</span><span>型糖尿病</span></p><p><span>礼来公司</span></p><p><span>39</span></p><p><span/></p><p><span>BMS-986036</span></p><p><span>阶段</span><span>2</span></p><p><span>II</span><span>型糖尿病，</span><span>NASH</span></p><p><span>BMS</span></p><p><span>40</span></p><p><span>卵巢移植</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>卵巢皮质移植</span></p><p><span>不适用</span></p><p><span>改善后代的生育能力</span></p><p><span/></p><p><span>41</span></p><p><span>手术切除内脏脂肪组织</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>手术切除内脏脂肪组织</span></p><p><span>第</span><span>2/3</span><span>期</span></p><p><span>胰岛素抵抗，肥胖，代谢综合征</span></p><p><span/></p><p><span>42</span></p><p><span>线粒体操纵</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>NAD +</span><span>前体</span></p><p><span>NAD +</span><span>前体</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>烟酰胺</span></p><p><span>市场补充</span></p><p><span>--</span></p><p><span/></p><p><span>43</span></p><p><span/></p><p><span>烟酰胺核苷（</span><span>NIAGEN</span><span>）</span></p><p><span>市场补充</span></p><p><span>--</span></p><p><span>Chromadex</span></p><p><span>44</span></p><p><span/></p><p><span>烟酰胺核苷</span><span>/</span><span>季戊二烯</span></p><p><span>市场补充</span></p><p><span>急性肾损伤</span></p><p><span>极乐世界</span></p><p><span>45</span></p><p><span>溶酶体功能改善</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>溶酶体调节剂</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>AT3375</span></p><p><span>临床前</span></p><p><span>帕金森氏症</span></p><p><span>弹药疗法</span></p><p><span>46</span></p><p><span/></p><p><span>PBT2</span></p><p><span>阶段</span><span>2</span></p><p><span>阿尔茨海默氏症和亨廷顿氏症</span></p><p><span>普拉纳生物技术</span></p><p><span>47</span></p><p><span/></p><p><span>溶酶体疗法</span></p><p><span>临床前</span></p><p><span>--</span></p><p><span/></p><p><span>48</span></p><p><span>AC5</span><span>抑制</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>SQ22,536 [9-</span><span>（四氢</span><span>-2-</span><span>呋喃基）</span><span>-9H-</span><span>嘌呤</span><span>-6-</span><span>胺</span><span>]</span><span>，维达拉滨（</span><span>9-β-D-</span><span>阿拉伯糖基腺嘌呤）和</span><span>NKY80</span></p><p><span>临床前</span></p><p><span>--</span></p><p><span/></p><p><span>49</span></p><p><span>DGAT1</span><span>抑制</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>PF-04620110</span></p><p><span>阶段</span><span>1</span></p><p><span>II</span><span>型糖尿病</span></p><p><span>辉瑞</span></p><p><span>50</span></p><p><span>PKA</span><span>抑制剂</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>H89</span><span>，</span><span>KT5720</span><span>，</span><span>PKI</span><span>类似物</span></p><p><span>临床前</span></p><p><span>--</span></p><p><span/></p><p><span>51</span></p><p><span>低糖毒素饮食</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>低年龄饮食</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>低年龄饮食</span></p><p><span>阶段</span><span>2</span></p><p><span>代谢综合征</span></p><p><span/></p><p><span>52</span></p><p><span>破碎时代</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>紫草属</span></p><p><span>第二阶段（已终止）</span></p><p><span>慢性心力衰竭</span></p><p><span>Synvista</span><span>治疗学</span></p><p><span>53</span></p><p><span/></p><p><span>苯丁胺</span></p><p><span>阶段</span><span>4</span></p><p><span>糖尿病肾病</span></p><p><span/></p><p><span>54</span></p><p><span>MIF-1</span><span>抑制</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>MIF-1</span><span>程序</span></p><p><span>临床前</span></p><p><span>--</span></p><p><span>卡洛斯疗法</span></p><p><span>55</span></p><p><span/></p><p><span>ISO-1</span></p><p><span>临床前</span></p><p><span>--</span></p><p><span/></p><p><span>56</span></p><p><span>α1-</span><span>肾上腺素能受体激动剂</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>Midodrinre</span></p><p><span>已批准</span></p><p><span>体位性低血压</span></p><p><span>夏尔</span></p><p><span>57</span></p><p><span>纤溶酶原激活剂</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>尿激酶</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>动解</span></p><p><span>批准（在返回市场的过程中）</span></p><p><span>肺栓塞，清除静脉导管中的血块</span></p><p><span>Microbix</span></p><p><span>58</span></p><p><span>PAI-1</span><span>抑制剂</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>TM5614</span></p><p><span>阶段</span><span>2</span></p><p><span>CP-CML</span></p><p><span>瑞纳科学</span></p><p><span>59</span></p><p><span>53</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>p53</span><span>基因治疗</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>p53</span><span>基因治疗</span></p><p><span>已批准（中国）</span></p><p><span>国家核安全委员会</span></p><p><span>SiBiono</span><span>基因技术</span></p><p><span>60</span></p><p><span>p53</span><span>激动剂</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>APR-246</span></p><p><span>阶段</span><span>2</span></p><p><span>卵巢癌</span></p><p><span>Aprea</span><span>治疗学</span></p><p><span>61</span></p><p><span>MDM2</span><span>拮抗剂</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>依地那林</span></p><p><span>第三阶段</span></p><p><span>反洗钱</span></p><p><span>罗氏</span></p><p><span>62</span></p><p><span>AgRP</span><span>抑制</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>TTP435</span></p><p><span>第二阶段（已停产）</span></p><p><span>肥胖</span></p><p><span>电视疗法</span></p><p><span>63</span></p><p><span>TRPV1</span><span>抑制</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>ALD403</span><span>（抗</span><span>CGRP</span><span>单抗）</span></p><p><span>第三阶段</span></p><p><span>慢性偏头痛</span></p><p><span>der</span><span>木</span></p><p><span>64</span></p><p><span/></p><p><span>LY2951742</span><span>（抗</span><span>CGRP</span><span>单抗）</span></p><p><span>第三阶段</span></p><p><span>慢性偏头痛</span></p><p><span>礼来公司</span></p><p><span>65</span></p><p><span/></p><p><span>AMG334</span><span>（抗</span><span>CGRP</span><span>受体单克隆抗体）</span></p><p><span>第三阶段</span></p><p><span>慢性偏头痛</span></p><p><span>安进</span></p><p><span>66</span></p><p><span/></p><p><span>TEV48125</span><span>（抗</span><span>CGRP</span><span>单抗）</span></p><p><span>第三阶段</span></p><p><span>慢性偏头痛</span></p><p><span>梯瓦</span></p><p><span>67</span></p><p><span>抑制肌生长抑制素</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>PF-06252616</span><span>（抗肌生成抑制素单克隆抗体）</span></p><p><span>阶段</span><span>2</span></p><p><span>DMD</span></p><p><span>辉瑞</span></p><p><span>68</span></p><p><span/></p><p><span>BMS-986089</span><span>（抗肌生成抑制素单克隆抗体）</span></p><p><span>第三阶段</span></p><p><span>DMD</span></p><p><span>BMS</span></p><p><span>69</span></p><p><span>亲环素</span><span>D</span><span>抑制</span></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span/></p><p><span>CC-1233</span></p><p><span>临床前</span></p><p><span>急性胰腺炎，神经变性</span></p><p><span>骨</span></p><p><span>70</span></p><p><span>诊所里有</span><span>70</span><span>种可能会使人寿命更长的药物</span><span>按作用机理排序</span></p><p><span>消息来源</span><span>：</span><span>请参阅表</span><span>2</span><span>的参考</span></p><p><span/></p><p><span>感谢</span><span>Patrick Collison</span><span>，</span><span>Daniel Gross</span><span>，</span><span>Elad Gil</span><span>和</span><span>Nate Sauder</span><span>鼓励我提出这个建议，以及</span><span>Nathaniel Horwitz</span><span>的主要编辑帮助。</span></p><p><span/></p><p><span/></p>