第三十章 长生不老药的传说
第三十章 长生不老药的传说
“鬼影，你他一娘一的跑哪儿去了，大家可都在等着你呢，石头的死，你得给老子一个交代。”宋乾坤脸色粒锲涠一硬。
“将军，你不该派石头跟踪我，我是一名侦探，我有我的自由。我想大家也都知道了，日本人已经控制了整座古墓，他们之所以还没对我们下手，是要利用我们帮他们寻找一样东西。”夏凌昊目光坚定，神情凝重，从他脸上看不出任何说谎的迹象。
“什么东西？”
“长生不老药。”
“扯淡！”
秦始皇迷恋长生不老药的传说在中国民间可谓家喻户晓，而这之后的一些帝王和方士也成了秦始皇的“忠实粉丝”。他们或修禅或炼丹，企图通过自己孜孜不倦的努力，以求达到长生不老的目的。他们从一开始就迷失了自我，目标充满幻想，计划毫无根据，行动荒诞可笑，当然结果也就只能惨淡收场了。从某种意义上讲，他们是一群顽固不化的“梦想家”，要知道理想和梦想是有差别的，所以历史的车轮毫不客气地碾碎了他们的梦。两千多年过去了，人们渐渐从长生不老的美好憧憬中走了出来，去品味现实生活中的酸甜苦辣，就连宋乾坤这样的大老粗也坚信，这个世界上根本没有长生不老药，那只是掌权者权欲熏心的产物，那只不过是一个美丽的传说。
夏凌昊轻蔑地一笑，继续说道：“石头和狗子都是被那些蒙面的黑衣人杀死的，我想你们也一定知道了他们的身份。不错，他们就是日本忍者。”说完，他还刻意盯了平川樱子一眼，樱子的目光中透着几分怯懦，她把头转向一边。
这时，巴特和肖俊向这边走来，巴特扯开嗓门，声音像洪钟一般响亮，“连长！石头就是这小子杀的，别听他狡辩！就让老子一崩了他，什么事情都解决了！”
肖俊按住巴特握的手，训斥道：“你太冲动了！鬼影是自己人，我相信他不会杀石头，听他把话说完！”肖俊故意摆出一副很相信“鬼影”夏凌昊的样子，他把目光投向夏墨林博士，夏凌昊是夏墨林博士的侄子，这个时候这位考古负责人总得说点什么吧？可他一改温文尔雅的面容，脸上反倒是冷若冰霜，不打算为侄子作任何辩护。肖俊的双眸登时闪过一丝失望。
夏凌昊针锋相对，冷冷地质问巴特：“二匪兄弟说我杀死石头，可有证据？”
巴特斩钉截铁地说：“我和石头跟踪你到暗室，接着石头就被人杀死了，当时就我们三个人在场，凶手不是你还会有谁！”
“二匪兄弟，你说的很对，当时就我们三个人在场，石头被人害死了，可我怎么就成了唯一的嫌疑人？这不符合正常的逻辑。再说了，堂堂七尺男儿，做事本该光明磊落，却竟干那跟踪别人的勾当，为天下英雄所不耻啊。”夏凌昊露出得意的笑容，他此时看上去不像是一个侦探，而像是一个站在陷阱上面俯瞰猎物的狡猾的猎人。
“你……”巴特想反驳，却无言以对，他此刻看肖俊时的眼神是充满抱怨的，他更不敢抬头正视宋乾坤。
“对对对，我向上帝保证，鬼影兄弟绝不是唯一的嫌疑人，这是明摆着的事，福尔摩斯他老人家不需要在这个时候显灵，连傻子都猜的出来。”杰克适时地插上一句，他还特别加重了“唯一”两个字的发音，他的傲慢他的自以为是，在很多时候都让人觉得这个长着粗鼻子蓝眼睛的美国飞行员是一个“没有立场”的人。
巴特是一个有血一性一的汉子，他虽勇一猛刚直，豪气干云，但却不善“脑力活”，当他发现自己被夏凌昊给绕进去之后，他登时怒不可遏，指着杰克的鼻子骂道：“放你一娘一的狗屁！石头是老子的生死兄弟，老子绝不会杀他！你这个死洋鬼子，再在这里胡说八道，看老子不打断你的狗腿！”
杰克无奈地耸耸肩，很识趣的退到一边，夏凌昊接着展开攻势，“你不用这么激动，大家都不会相信你是凶手，可我确实没有杀石头。我和石头都进入了暗室这不假，但事情绝不会像你想象的那样简单，现场会是只有我们三个人。你当那些忍者是透明人，不存在吗？我是一名侦探，任何蛛丝马迹都逃不过我的眼睛，我通过暗室里的机关找到了忍者的藏身地点，并与他们展开了一场殊死搏斗。其实……我也受了重伤！”说完，“鬼影”夏凌昊哇的一声吐出一口鲜血，身一子晃了几下，差点昏倒在地上。
特遣队的医务兵替夏凌昊查看伤势，发现他的前胸和后背都有许多刀伤，最严重的是左胸部位的一刀，匕首整个没入体内，刀锋偏离心脏不到一公分。医务兵在给夏凌昊处理伤口的同时，肖俊也在心里暗自嘀咕：那些忍者不是都用倭刀的吗？那鬼影左胸上插着的那把匕首是怎么回事？
夏凌昊脸色苍白，豆大的汗珠从额头上渗出来，顺着两颊钻进脖子里，他强忍住剧痛，一声不吭。巴特看在眼里，不禁对夏凌昊刮目相看。他说话的语气也明显缓和下来，“鬼影，老子不是曹一操一那孙子，不喜欢猜忌别人。可有些事情我还是弄不明白，你说你跟那小日本的什么狗屁忍者干了一仗，我咋就没看见呢？”
“暗室里除了机关还有暗道，当时忍者不敌于我，就通过暗道逃跑了，我一路追杀过去，最后将其斩杀。所以，你和石头前后进入暗室，却都没有发现我的影子。”夏凌昊长舒一口气，从黑色风衣的口袋里拿出一张白纸，交到宋乾坤手上，“将军，这是从斩杀的忍者的尸体上找到的，上面清楚地记载了有关长生不老药的传说。”
宋乾坤接过白纸，只见上面是从某处石刻上拓下来的一些奇怪的字体。邦妮站在宋乾坤身后，俏皮地踮起脚，偷偷地看了一眼，在心里对自己说：这不是詹姆斯教授说的衣淖致铮切┤陶咔狈一在沙俑的体内，一定是他们从暗室的墙上拓下来的。
“博士，您看过这些字，上面到底写了些什么？您可别瞒我，咱虽然是一个大老粗，识不了几个字，可咱会看人。特遣队算是拼光了，可原来有几百号人，哪个士兵一撅腚，老子就知道他小子拉的什么屎，哪个士兵的眼睛这么滴溜溜一转，老子就知道他狗日的耍什么心眼。您看您是有文化的人，犯不着跟咱这些没文化的泥腿子藏着掖着不是？放心吧，老爷子，没人跟您抢状元，就是‘秀才’也没那本事，他虽然读过不少书，也挺有见识的，可他顶多也就是一秀才，要戴那状元的帽子，恐怕还不够格。所以呀，您今天无论如何也得说实话。”宋乾坤不是一个好奇心重的人，他压根就不相信这个世界上会有什么长生不老药，可他心里跟明镜似的，夏墨林博士一定知道些什么。夏墨林博士越是藏着掖着，他就越想撬开对方的嘴，因为他是一个豪爽的人，是一个有血一性一的汉子，在他十几年的戎马生涯中，始终持这样一个信条：宁肯打败仗，也绝不允许别人欺骗自己！
夏墨林博士笑的有些苦涩，说道：“将军，你是爽一快人，老朽本来就没打算瞒你什么。这个拓本上的字正是古楼兰人发明的衣淖郑馍厦娴娜诽岬搅擞美戳吨瞥ど焕弦┑奶焐窖┝　
众人听到“天山雪莲”四个字，惊诧不已，在汉族人眼里，这是一种“神药”。千百年来，它始终和“长生不老”有着千丝万缕的联系。天山雪莲，又名“雪荷花”，维吾尔语称其为“塔格依力斯”，是新疆特有的珍奇名贵中草药。它生长在天山山脉海拔4000米左右的悬崖陡壁之上、冰渍岩缝之中；那里气候严寒、终年积雪不化，一般植物根本无法生存，而雪莲却能在零下几十度的严寒和空气稀薄的缺氧环境中傲霜斗雪、顽强生存。素有“百草之王”和“药中极品”的美誉。晋《穆天子传》云，天子向王母求长生不老药，王母取天山雪莲赠之。另外，《史记》、《本草纲目》、《山海经》等均有对雪莲神奇药用价值的记载。
夏墨林博士接着说道：“天山雪莲中最名贵的一种叫‘血莲’。这种药物和普通的雪莲一样有很高的药用价值，不同的是，它的药一性一可能更强更奇特。普通的雪莲从种子萌发到一抽一苔开花需要六到八年的时间，而血莲的生长期则是这个数的十倍。楼兰王安归伽的妻子光月王后没出阁以前就住在天山天池，衣氖樯纤担薷ダ纪醯那耙惶焱底吡俗謇锏氖ノ铮飧鍪ノ镎茄＞菟邓梢允谷似鹚阑厣⒀幽暌媸佟！
詹姆斯教授补充道：“这么说，那些忍者也是冲着血莲来的，日本人控制这座古墓的真正目的是想得到长生不老药。”
炮手兼排雷手胡山狠狠地啐了一口唾沫，“当年徐福东渡扶桑替秦始皇炼制什么长生不老药，两千年后，他的徒子徒孙们又千里迢迢来到中国寻找什么血莲，看来，狗日的小鬼子真是鬼迷心窍了！”
“对了，樱子小一姐不是说，小鬼子在楼兰建立了细菌战实验基地嘛，我看这不过是掩人耳目，他们真正的目的就是要在这里用血莲炼制长生不老药，然后供给他们的作战部队，这样他们就可以永久的占领中国了。好大的野心！咱们必须赶在小鬼子前头找到血莲，不然就麻烦了！”巴特是个直一肠子，心里有什么就说什么，他的“鲁莽”引来杰克的一阵嘲笑。
宋乾坤脸上挂不住面子，训斥道：“你小子当那血莲是山坡上的草，一抓一大把？小鬼子还炼制长生不老药，供给他们的作战部队？亏你想的出来！再说了，要真能炼制出长生不老药，那也是咱中国人该干的事，还轮不到他小鬼子在咱国土上班门弄斧！”
巴特嘿嘿一笑，“连长教训的是，连长教训的是，俺也就那么随口一说，连长咋能当真呢！”
“也许血莲正是日本人进行细菌战试验所必需的一种药物。”始终默默不语的平川樱子突然开口。她的话令所有人震惊，古墓里鸦雀无声，空气也仿佛凝结了。
“樱子小一姐，别忘了你也是日本人。”代号为“白狐”的特派员方雁云又把宋乾坤拉到一边，“将军，樱子向我们透漏了这么多关于日本人进行细菌战试验的秘密，这可不太正常，她……”
“白狐，我虽然是一个日本人，但我讨厌战争，我是一个一爱一好和平的人，我非常希望中日两国能尽快结束这场没有意义的厮杀。”平川樱子似乎有意要打断方雁云和宋乾坤之间的私语。
“将军，没有战场上的胜利做筹码，和平根本就是空谈！现在我们的处境很不妙，希望你能谨慎从事。”白狐方雁云不再和宋乾坤私语，反而故意提高了嗓门，目的是让平川樱子听得清清楚楚，也希望借此能“点化”宋乾坤。
宋乾坤虽然不喜欢白狐，但他觉得她说的还是蛮有道理，可他仍然一语不发，静静地思考起来。这时，夏墨林博士轻轻一抚一摸一着樱子的脑袋，转而对方雁云说：“白狐，我和樱子的父亲是很要好的朋友。樱子她心地善良、一爱一好和平，这一点我可以用我的一性一命作担保，还请你不要对樱子有太多的成见。”
“哼，博士的朋友可真多啊，有些人外表看上去柔一弱可亲，可她内心里在想些什么谁也不知道。将军，博士，党国的利益高于一切，如果哪一天要真发生点什么不愉快的事情，可别怪我没提醒你们！”方雁云冷冷地说道。
“白狐，我和我的兄弟们都是从死人堆里爬出来的，我们为党国浴血奋战，为人民战死沙场，要论功行赏，我们个个都该记一等功！可老子对那张破纸不敢兴趣，你也没资格威胁老子！”宋乾坤说完，方雁云的脸气得通红，她的职位比宋乾坤要高，她也很想发作，但周围特遣队战士们的几十双眼睛正恶毒的盯着自己，她只得忍气吞声。
夏凌昊在医务兵的搀扶下勉强站起身来，说道：“将军，我在古墓里也发现了一些蛛丝马迹，据我推测，日本人煞费苦心想得到血莲，并不见得就是为了炼制什么长生不老药，血莲未必就真有长生不老的功效。也许他们正在进行的细菌战试验需要一种长久不衰的病原体，而血莲可以帮助他们达到这种目的。”
“不管日本人的目的是什么，肯定和惫罴仆巡涣烁上担颐潜匦胱柚顾牵　敝傅荚毙た∠蛳牧桕煌度ピ扌淼哪抗猓肮碛埃幌氲侥阋彩兜衣淖郑植坏弥劳乇旧霞窃氐哪谌荩绕鸩┦坷矗阏婵晌角喑鲇诶抖び诶叮　
夏凌昊淡然一笑，“这没什么好夸耀的，我自小跟随叔父，也曾识得几个古文字。拓本上的大体内容我也解读不出来，只识得‘长生’几个字样而已。”
话音刚落，夏墨林博士指着夏凌昊的鼻子大声呵斥道：“你根本就不是我的侄儿！”
所有的人都被惊呆了，他们盯着夏凌昊看了半天，心中不自觉地筑起一道防线。夏墨林博士接着说：“我教过昊儿怎么解读甲骨文、铭文、还有古埃及文字，却从来没有教过他如何解读衣淖帧Ｋ裕闶歉雒芭苹酰「嫠呶遥闶撬渴遣皇侨毡救伺赡憷吹模课业闹蹲酉衷谠谀睦铮俊
宋乾坤听到这里，不容“夏凌昊”辩解，一操一起鬼头大刀指着后者的鼻子，怒不可遏地说道：“你他一娘一的到底是谁？！”
突然，从“夏凌昊”风衣的袖子里弹出一把四尺三寸长的软剑。软剑像一条吐着红色信子的灵蛇将宋乾坤的鬼头大刀死死缠住，这倒是出乎所有人的意料。宋乾坤也懵了，“夏凌昊”抓住这短暂的喘息时机，手腕略微一抖，软剑如同一条卷着波一浪一的丝带刺向宋乾坤的胸膛，宋乾坤急忙一抽一刀格挡，谁知这竟是虚招，“夏凌昊”立刻收回软剑，几个箭步蹿到墓室门口。通讯员王冶端起冲锋准备扫射，却被肖俊阻止，因为他看见“夏凌昊”并没有要逃走的意思，反而用手撕下了脸上的人皮面具，一张冷俊刚毅的脸呈现在众人面前。世上真的有长生不老、起死回生的仙药吗？Novartis诺华科学家正试图证明它的存在
Gistec Prima, PT业务经理
世上真的有长生不老、起死回生的仙药吗？年营业额达 2600 亿美元的瑞士Novartis (诺华) 大药厂的科学家正在试图证明它的存在。1964年一个加拿大的科学探测队到南太平洋的复活节岛募集植物与土壤标本。在巨型石像群底下收集了一些土壤标本。后来将所采集的微生物与AYERST 研究实验室共享（AYERST 为加拿大蒙特利尔的一个药厂）。1972年，在该实验室工作的巴基斯坦裔微生物化学科学家 SUREN SEHGAL (全名 Surendra Nath Sehgal, PhD.)从微生菌 Streptomyces hygroscopicus 代谢物里分离出一种抗生素，命名为 rapamycin. 他发现rapamycin是很好的抗炎剂。后来发现它具有抑制器官移植排斥反应的奇异功能。1999年，美国FDA 食品药品监督管理局正式准许rapamycin 成为供器官移植病人服用的抗排斥反应的药物。过后不久，Suren Sehgal 即死于癌症，看不到他研究出来的奇药救活了数以千计的病人与它带给药厂数亿美元的利润。自1990年起，Sandoz （诺华的前身）科学家就发现rapamycin的分子能够阻止细胞里管理生长与代谢的通道。此通道被发现存在于所有的从单细胞酵母到人体各细胞内，并被命名为rapamycin 目标 - target of rapamycin" 或 TOR。哺乳动物细胞的TOR 则特被命名为 mTOR。此mTOR 掌握了细胞里的新陈代谢速度。欲知如何，请阅英文全文。Streptomyces hygroscopicus只存在于复活节岛上。Sehgal发现了ramamycin 的来源February 12, 2015Does a Real Anti-Aging Pill Already Exist？Inside Novartis’s push to produce the first legitimate anti-aging drugby Bill Gifford， Bloomberg BusinessWeekOne afternoon in the early 1980s, Suren Sehgal brought a strange package home from work and stashed it in his family’s freezer. Wedged beside the ice cream, it was wrapped in heavy plastic and marked, “DON’T EAT!” Inside were several small glass vials containing a white paste—all that remained of a rare bacterium that today is the foundation of the most promising anti-aging drug in decades. Sehgal had been studying it since 1972, when he’d first isolated it in a soil sample at Ayerst Laboratories, a pharmaceutical company in Montreal.A Canadian medical expedition had collected the soil from beneath one of the mysterious stone heads on Easter Island, a speck in the middle of the Pacific Ocean. In the dirt, Sehgal had discovered Streptomyces hygroscopicus, a bacterium that secreted a potent antifungal compound. T he thought perhaps it could be made into a cream for athlete’s foot or other fungal conditions. He purified the stuff and named it rapamycin, after Easter Island’s native name, Rapa Nui.It soon proved its potential. When a neighbor’s wife developed a stubborn fungal skin condition, Sehgal mixed up a rapamycin ointment for her. “It was probably illegal,” says his son Ajai Sehgal, but the infection cleared up quickly. Suren, a biochemist who’d immigrated to Canada from a tiny village in what’s now Pakistan, became convinced that he’d stumbled upon something special. Before he could develop it any further, however, Ayerst abruptly closed its Montreal lab, and his bosses ordered all “nonviable” compounds destroyed—including the rapamycin. Sehgal couldn’t bring himself to do it and instead squirreled a few vials of Streptomyces hygroscopicus into his freezer at home. Most of the staff was fired, but Sehgal was transferred to the company’s lab in Princeton, N.J. The plastic package made the move packed in dry ice.When Wyeth, the global health-care company based in Pennsylvania, bought Ayerst in 1987, Sehgal persuaded his bosses to let him resume his work on the rare bacterium. Sehgal found that, besides its antifungal properties, rapamycin also suppressed the immune system. It tamps down the body’s natural reaction to a new kidney or other organ. Eventually, in 1999, the U.S. Food and Drug Administration approved rapamycin as a drug for transplant patients. Sehgal died a few years after the FDA approval, too soon to see his brainchild save the lives of thousands of transplant patients and go on to make Wyeth hundreds of millions of dollars.In the years since, rapamycin has been adapted for numerous uses. Like penicillin, it’s a biological agent, so it can’t be patented, although derivatives of it can. It’s now used routinely as a coating on cardiac stents to prevent scarring and blocking. Derivatives of rapamycin have been approved for use against certain kidney, lung, and breast cancers. That may be just the beginning. Over the past decade, it’s shown promise as a drug that not only can extend life by delaying the onset of aging-related diseases such as cancer, heart disease, and Alzheimer’s disease, but also postpone the effects of normal aging. With an eye toward changing the way millions grow older, Novartis, the $260 billion Swiss pharmaceutical giant, has begun taking the first steps to position a version of rapamycin as the first true anti-aging drug.Pharmacological history is full of substances that have been purported to delay aging or lengthen life span, from resveratrol (the “red wine pill”) in the 2000s to testicular implants in the 1920s, all the way back to medieval alchemists (gold was thought to possess anti-aging properties). Until rapamycin came along, however, nothing has actually worked in rigorously designed clinical studies.“People have shown that rapamycin extends life span again and again and again,” says Matt Kaeberlein, a scientist at the University of Washington and a leading researcher in the biology of aging. So far it’s demonstrated it can lengthen the lives of mice, not men, but what’s particularly exciting is how it did so, Kaeberlein says. The drug appears to delay “age-related decline in multiple different organ systems, which is something we would expect if we were fundamentally slowing the aging process.”The promise of rapamycin, he and others contend, is to treat aging as a contributing factor to the chronic diseases that kill people later in life, the way we now lower cholesterol to prevent heart disease. “I view it as the ultimate preventive medicine,” says Kaeberlein, who’s leading a rapamycin study on dogs.Not everyone is convinced. “There are no interventions that have been documented to slow, stop, or reverse aging in humans,” says S. Jay Olshansky, a professor of public health at the University of Illinois at Chicago and a leading critic of purported life-extending supplements and treatments. “The batting average is zero.”Olshansky welcomes the advent of therapies like rapamycin, but he doesn’t think we know enough yet: “My caution is always no, no, no: Let science do what it does and evaluate these interventions for safety and efficacy first,” he says. Such admonitions are justified. And yet the enthusiasm of scientists such as Kaeberlein is hard to resist. “We have the potential to delay the onset of all of these diseases at the same time by understanding and intervening in the molecular processes that drive aging,” he says. “We now know that that is possible.”Rapamycin works at a fundamental level of cell biology. In the early 1990s, scientists at Novartis’s predecessor, Sandoz, discovered that a rapamycin molecule inhibits a key cellular pathway regulating growth and metabolism. This pathway was eventually dubbed “target of rapamycin,” or TOR, and it’s found in everything from yeast to humans (it’s known as mTOR in mammals).MTOR is like the circuit breaker in a factory: When it’s activated, the cell grows and divides, consuming nutrients and producing proteins. When mTOR is turned down, the “factory” switches into more of a conservation mode, as the cell cleans house and recycles old proteins via a process called autophagy. One reason caloric restriction extends life span in animals, researchers believe, is because it slows down this mTOR pathway and cranks up autophagy. Rapamycin does the same thing, only without the gnawing hunger.“Really what rapamycin is doing is tapping into the body’s systems for dealing with reduced nutrition,” says Brian Kennedy, chief executive officer of the Buck Institute for Research on Aging in Novato, Calif. “We’ve evolved over billions of years to be really good at that. When things are good, we’re going to grow and make babies. And when things are not so good, we go into a more stress-resistant mode, so we survive until the next hunt. And it just so happens that stress resistance is good for aging.”One of the most passionate advocates for rapamycin as an anti-aging drug is a Russian scientist named Mikhail Blagosklonny, who now works at the Roswell Park Cancer Institute in Buffalo. A native of St. Petersburg, he was working on cancer treatments in the early 2000s when he realized the same qualities that made rapamycin effective at slowing tumor growth might also help it slow the aging process. He became so convinced of rapamycin’s potential, and its safety, that he tried it himself. “Some people ask me, is it dangerous to take rapamycin?” Blagosklonny says. “It’s more dangerous to not take rapamycin than to overeat, smoke, and drive without belt, taken together.”Many colleagues have regarded his advocacy as a bit over-the-top. When Blagosklonny submitted papers to major journals making these arguments, they were brutally rejected. “Sometimes, the reviewers would call me names,” he says. That started to change in 2009, when a large National Institutes of Health-funded study established that rapamycin and its derivatives helped mice live longer. The NIH scientists started mice on the drug at 20 months, or late middle age in mouse terms (mice typically live two to three years). Male mice on rapamycin lived 9 percent longer. The females’ life span was extended by 14 percent. This is roughly the equivalent of giving 60-year-old women a pill that would enable them to see their 95th birthday.There’s one catch: Rapamycin suppresses the immune system (that’s why it’s effective with transplants). That fact, many scientists and physicians believe, is its Achilles’ heel as a drug to treat aging. Giving such a drug to older patients, whose immune systems are often already diminished, would make them vulnerable to life-threatening infections, defeating the purpose.For believers like Blagosklonny, a breakthrough came on Christmas Eve 2014. That’s when a paper appeared in Science Translational Medicine, part of the Science family of journals. According to the study, conducted with volunteers in Australia and New Zealand, a derivative of rapamycin called everolimus had been shown to improve the immune response of elderly patients when administered in limited doses. It wasn’t the sort of thing that makes CNN, but in the world of scientists who work on human aging, it was big. “A watershed,” says Nir Barzilai, director of aging research at New York’s Albert Einstein College of Medicine.For the first time, the study showed, rapamycin appeared to enhance aspects of the immune response, boosting the efficacy of a flu vaccination in the study population, who were all 65 or older. “It seems to modulate the immune response, not suppress it,” says Barzilai. “It’s very exciting.” The study was noteworthy also because Novartis paid for it. For the most part, Big Pharma has shied away from aging, which conventional wisdom had deemed to be a quackery-ridden money pit. In 2008, GlaxoSmithKline paid $720 million to buy Sirtris Pharmaceuticals, a biotech startup founded by Harvard professor David Sinclair that was developing drugs based on resveratrol, the antifungal compound found in the skins of red-wine grapes. Resveratrol received a tremendous amount of coverage in the media, including 60 Minutes, the New York Times, and Barbara Walters. It was said to be responsible for the “French paradox”: Although the French eat fatty foods, they remain healthy. A highly publicized Nature paper had shown that mice on a high-fat diet had lived longer with resveratrol. After the study appeared, sales of resveratrol supplements rocketed from basically zero to about $100 million a year. But the drugs all flopped in human trials, and in 2013 GSK shuttered its Sirtris division and fired all but a handful of staffers.“The difference between rapamycin and resveratrol is that rapamycin really works as advertised and resveratrol doesn’t,” says the University of Washington’s Kaeberlein. “If you look at the data, you have to agree.” Kaeberlein, who went to graduate school with Sinclair at MIT, was an early critic of resveratrol, which he points out has actually never extended life span or otherwise slowed aging in normal mice—it appeared to work only in fat mice.Rapamycin has been found to reduce age-related bone loss, reverse cardiac aging, and reduce chronic inflammation in mice. It’s even been shown to reverse Alzheimer’s disease in them. The Novartis study was the first to examine rapamycin’s effect on aging-related parameters in healthy older people. “It’s a landmark study,” says the Buck Institute’s Kennedy. “It’s the kind of study we need more of.”That doesn’t mean everyone should be asking their doctors for a prescription to an mTOR inhibitor. Critics say it may be too risky for people who are otherwise fine. Besides the possibility of immune suppression, rapamycin’s side effects can include canker sores and impaired wound healing. “Rapamycin works on pathways that are too fundamental to normal cellular function to be used as a drug in healthy people until we have much more safety data,” says Valter Longo, a professor at the University of Southern California who discovered key pathways related to TOR. He points out that periodic fasting also shuts down the same pathways, without the side effects.The Novartis researchers tried to get around the immune-suppression side effect by giving the drug in very low doses and for a defined period. They found its benefits persisted long after the drug was discontinued. But the Novartis study is far from definitive on the issue, says Janko Nikolich-Zugich, chair of the department of immunobiology at the University of Arizona and co-director of the Arizona Center on Aging.The study measured response to a vaccine, not to an infectious agent. Nikolich-Zugich fears that rapamycin would stop immune cells from multiplying quickly enough to fight off an army of invading pathogens. “I don’t think this in any way, shape, or form settles concerns about what mTOR inhibitors would do in cases of infection,” he says.An innovative clinical trial set to begin in March may resolve some of these issues. Kaeberlein and his University of Washington colleague Daniel Promislow plan to test the drug in small doses in middle-aged pet dogs. Rather than looking at life span, which would take years, they will look for signs that the drug is affecting key aging-related parameters, such as arterial stiffness and cardiac function. If successful, rapamycin and its derivatives could end up as the first anti-aging drug—for dogs. Kaeberlein wouldn’t mind: “I love my dogs,” he says. “If there’s anything we can do to make them live longer, healthier lives, we have to do it. I feel like I personally have to do this.”In September, Novartis Chairman Joerg Reinhardt announced the company’s new commitment to aging research. “Over the long term, one could argue that R&D productivity has relentlessly declined,” he said in a keynote at a drug development conference in Basel, Switzerland. Aging represents a fertile field of discovery: Identifying the pathways and proteins associated with aging could yield promising drug targets, he said. By tweaking the right pathways, researchers could theoretically prevent a host of age-related diseases. Novartis is not alone in this: Chicago-based AbbVie has complete a $750 million partnership with Calico, an aging-research venture founded by Google.Rapamycin isn’t the only widely used medication that’s turning out to have possible anti-aging properties. Millions of diabetics take a drug called metformin, which has been around for decades. Like rapamycin, metformin extended the life of federally funded mice in a clinical trial. And there is evidence that it might do the same for people. Diabetes typically shaves about five years off a person’s life. But a large retrospective analysis found that diabetics on metformin had a 15 percent lower mortality rate than nondiabetic patients in the same doctors’ offices. “To me that suggests that it’s actually targeting aging,” says Kennedy. The problem they’ll all face, though, is the same one that tripped up GSK: The FDA is unlikely to approve any drug intended to “treat” aging, because aging is not considered a disease. Another obstacle is the high safety standards required of any drug that would, in effect, be used to treat healthy people. “It would have to have fewer side effects than aspirin,” says Randy Strong, a pharmacologist at the University of Texas Health Science Center at San Antonio who worked on the 2009 NIH study.This may explain why Novartis is taking an incremental approach with therapies aimed at specific conditions, says Dr. Mark Fishman, head of the Novartis Institutes for BioMedical Research in Cambridge, Mass., and a member of the company’s executive committee. “We’re therapeutically oriented, rather than looking for the pill that will make everybody live to 120,” he says.The company’s age-related drug pipeline includes a novel drug aimed at treating heart failure, which the European Union recently fast-tracked for approval. Another, bimagrumab, is meant to reverse muscle loss. Designated a “breakthrough” by the FDA, it’s soon set to enter Phase III clinical trials for a rare condition called sporadic inclusion body myositis, but it could have wider application for muscle wasting and frailty in older people. “This whole frailty business is right up there with Alzheimer’s as a cause of incapacitation and sadness for the elderly,” Fishman says.Also in the works are a drug that could potentially restore cartilage in aging joints and, most interestingly, a radical gene therapy meant to reverse the loss of “hair cells” in the ear canal that are crucial for good hearing, but which are knocked out by things like antibiotics, chemotherapy, and “too much Lady Gaga,” Fishman says. He’s cautious about the anti-aging potential of rapamycin, a derivative of which the company sells under the Afinitor brand name for cancer treatments and as Zortress for transplants, with 2012 sales of just more than $1 billion. (Pfizer, which purchased Wyeth in 2009, also sells a version under the brand name Rapamune.) “I remain skeptical that there will be one magic bullet,” Fishman says, “but [the 2014 study] is a good proof-of-concept, and it’s provocative enough that we’ll at least think of how and whether we should proceed.”Blagosklonny isn’t so measured or patient. In his view, rapamycin has been approved for use for more than 15 years, with no serious problems reported. “I have read all papers about side effects,” he says, “and there are less side effects than with aspirin.” When he took it, he says, it made him feel better, “like with exercising.”Novartis strongly discourages such off-label use. In an e-mail, spokeswoman Mariellen Gallagher wrote: “It is far too early to tell whether low-dose rapamycin will lengthen human life span. A favorable risk/benefit ratio needs to be demonstrated in clinic trials to be sure that mTOR inhibitors such as rapamycin have acceptable safety and efficacy in aging-related conditions in humans.”In any case, one imagines Sehgal would be proud. After he was diagnosed with cancer in 1998, his son Ajai says, Sehgal began taking rapamycin, too—despite the drug not having been approved for anything yet. He had a hunch that it might help slow the spread of his cancer, which had metastasized to his liver and other organs. His doctors gave him two years to live, but he survived for much longer, as the tumors appeared to go dormant. The only side effect he suffered from was canker sores, a relatively small price to pay.But in 2003, after five years, Sehgal, age 70, decided to stop taking the drug. Otherwise, he told his wife, he’d never know whether it was really holding back his cancer. The tumors came back quickly, and he died within months, says Ajai. “On his deathbed, he said to me, ‘The stupidest thing I’ve ever done is stop taking the drug.’ ”Gifford is the author of Spring Chicken, a book about the science of aging, published in February.