As researchers on aging noted recently, no treatment on the market today has been proved to slow human aging - the build-up of molecular and cellular damage that increases vulnerability to infirmity as we grow older. 研究抗衰老的科学家最近指出，目前市面上没有任何疗法被证实可以延缓衰老。随着我们年龄的增长，分子和细胞损害慢慢积累，这导致我们的健康状况变得很脆弱。 But one intervention, consumption of a low-calorie* yet nutritionally balanced diet, works incredibly well in a broad range of animals, increasing longevity and prolonging good health. 但是最近有一项试验，即摄入低卡路里而营养均衡的饮食，在多种动物身上都得到了显著效果，不仅延长了动物的寿命，也提高了他们的健康水平。 Those findings suggest that caloric restriction could delay aging and increase longevity in humans, too. 这一发现意味着限制卡路里摄入可以延缓衰老并且延长人类寿命。

Unfortunately, for maximum benefit, people would probably have to reduce their caloric intake by roughly thirty per cent, equivalent to dropping from 2,500 calories a day to 1,750. 遗憾的是，为了使效果最大化人类可能需要将卡路里摄入降低 30%左右，这相当于每日卡路里 摄入从 2500 下降到 1750。 Few mortals could stick to that harsh a regimen, especially for years on end. 没有多少人能够坚持这样严酷的养生法，尤其是常年坚持。 But what if someone could create a pill that mimicked the physiological effects of eating less without actually forcing people to eat less? 但是如果有人发明出一种药物来效仿减少饮食的生物学效果而无需真的减少饮食呢？ Could such a ‘caloric-restriction mimetic', as we call it, enable people to stay healthy longer, postponing age-related disorders (such as diabetes, arteriosclerosis, heart disease and cancer) until very late in life? 这种我们称为“卡路里限制替代” 的药物能够使人们的健康保持的更长久，从而使老年病（如糖尿病、动脉硬化、心脏病、癌症）的发生向后推迟吗？ Scientists first posed this question in the mid-1990s, after researchers came upon a chemical agent that in rodents seemed to reproduce many of caloric restriction's benefits. 科学家最初提出这个问题是在 20 世纪 90 年代中期，那时他们刚刚发现了一种化学制剂，它在啮齿类动物体内似乎能够产生很多卡路里限制效应。 No compound that would safely achieve the same feat in people has been found yet, but the search has been informative and has fanned hope that caloric-restriction (CR) mimetics can indeed be developed eventually. 目前，科学家还没有合成出能够在人体 内达到相同功效的化合物，但是研究工作还是卓有成效的，科学家相信，卡路里限制替代品最终是可以研发出来的。

The benefits of caloric restriction The hunt for CR mimetics grew out of a desire to better understand caloric restriction's many effects on the body. 卡路里限制的好处寻找卡路里限制替代品的动机，源于人们想要更好的理解卡路里限制为人体带来的诸多效应。 Scientists first recognized the value of the practice more than 60 years ago, when they found that rats fed a low-calorie diet lived longer on average than free-feeding rats and also had a reduced incidence of conditions that become increasingly common in old age. 科 学家最初意识到这一点的价值是在 60 多年前，那时他们发现，饮食中卡路里含量低的小白鼠与饮食中卡路里含量正常的小白鼠相比，寿命更长，并且也不容易患上老年期很常见的疾病。 What is more, some of the treated animals survived longer than the oldest-living animals in the control group, which means that the maximum lifespan (the oldest attainable age), not merely the normal lifespan, increased. 不仅如此，对照组中有几只小白鼠的寿命比控制组中最长寿的小白鼠还要长，这不仅意味着正常寿命值有所增加，最大寿命也有所提高。 Various interventions, such as infection-fighting drugs, can increase a population's average survival time, but only approaches that slow the body's rate of aging will increase the maximum lifespan. 有很多种外在作用（如注射抗感染药物）都可以提高人群的平 均生存时间，但是只有能够降低人体衰老速度的方式才能够提高最大寿命值。

The rat findings have been replicated many times and extended to creatures ranging from yeast to fruit flies, worms, fish, spiders, mice and hamsters. 小白鼠身上的试验已经被重复了很多次，并且范围也扩大到了各种生物，如酵母、果蝇、蠕虫、 鱼、蜘蛛、老鼠、仓鼠等。 Until fairly recently, the studies were limited to short-lived creatures genetically distant from humans. 直到不久前，研究还局限于那些基因与人类差异较大的短寿命生物身上。 But caloric-restriction projects underway in two species more closely related to humans - rhesus and squirrel monkeys - have made scientists optimistic that CR mimetics could help people. 但是最近在与人类基因关系密切的恒河猴和松鼠猴身上进行的相关研究却使科学家更加乐观地相信，CR 技术可以对人类有所帮助。

The monkey projects demonstrate that, compared with control animals that eat normally, caloric-restricted monkeys have lower body temperatures and levels of the pancreatic hormone insulin, and they retain more youthful levels of certain hormones that tend to fall with age. 对猴的研究表明，相对于饮食正常的控制组而言，进行卡路里限制的猴子的体温较低，胰岛素分泌量也较低，而某些随年龄增长而呈下降趋势的激素，在这些猴子的体内也能保持在年轻时的水平。

The caloric-restricted animals also look better on indicators of risk for age-related diseases. 进行卡路里限制的猴子在一些老年病指标上也表现甚佳。 For example, they have lower blood pressure and triglyceride levels (signifying a decreased likelihood of heart disease), and they have more normal blood glucose levels (pointing to a reduced risk for diabetes, which is marked by unusually high blood glucose levels). 例如，它们的血压和甘油三酸酯偏低，意 味着它们患心脏病的概率降低；血糖更加正常，意味着患糖尿病的概率降低。 Further, it has recently been shown that rhesus monkeys kept on caloric-restricted diets for an extended time (nearly 15 years) have less chronic disease. 另外，试验表明，恒河猴的卡路里限制如果能保持的更久，如 15 年，则其所患的慢性病也较少。 They and the other monkeys must be followed still longer, however, to know whether low-calorie intake can increase both average and maximum lifespans in monkeys. 然而，要对这些猴进行更长的追踪才能了解是否低卡路里摄入能够确实增加猴子的平均寿命和最大寿命。 Unlike the multitude of elixirs being touted as the latest anti-aging cure, CR mimetics would alter fundamental processes that underlie aging. 与众多被吹捧为最新抗衰 老药的药物不同的是，CR 技术将会从根本上改变一些导致衰老的生物学进程。 We aim to develop compounds that fool cells into activating maintenance and repair. 我们的目标是研发出一 种药物用以诱导细胞进行自主修复。

How a prototype caloric-restriction mimetic works The best-studied candidate for a caloric-restriction mimetic, 2DG (2-deoxy-D-glucose), works by interfering with the way cells process glucose. 卡路里限制模拟机制如何发生作用研究最透彻的卡路里限制替代品要数 2DG（二脱氧 D 葡萄糖），它能够影响细胞加工葡萄糖的方式。 It has proved toxic at some doses in animals and so cannot be used in humans. 在动物体内应用到一定剂量时，它是有毒的，所以还不能够用于人体。 But it has demonstrated that chemicals can replicate the effects of caloric restriction; the trick is finding the right one. 但是我们确信，可以通过药物来产生卡路里限制的效应，问题就在于哪种药物比较合适。

Cells use the glucose from food to generate ATP (adenosine triphosphate), the molecule that powers many activities in the body. 细胞把食物中获取的葡萄糖用于生成 ATP（三磷酸腺苷），这种分子为体内的很多活动提供能量。 By limiting food intake, caloric restriction minimizes the amount of glucose entering cells and decreases ATP generation. 通过限制食物摄入，卡路里限制作用使进入细胞的葡萄糖数量降至最低从而减少 ATP 的生成。 When 2DG is administered to animals that eat normally, glucose reaches cells in abundance but the drug prevents most of it from being processed and thus reduces ATP synthesis. 当 2DG 被注入正常饮食的动物体内时，葡萄糖仍然大量涌向细胞，但是该药物可以防止大部分葡萄糖得到加 工，从而减少 ATP 的合成。 Researchers have proposed several explanations for why interruption of glucose processing and ATP production might retard aging. 对于干预葡萄糖反应以及 ATP 生成为什么可能延缓衰老，科学家提出了几种解释。 One possibility relates to the ATP-making machinery's emission of free radicals, which are thought to contribute to aging and to such age-related diseases as cancer by damaging cells. 一种解释与 ATP 生成过程中释放出的自由基有关，自由基被认为会通过破坏细胞而导致衰老 以及老年病（如癌症）。 Reduced operation of the machinery should limit their production and thereby constrain the damage. 降低 ATP 生成的反应可以减少自由基的形成，从而减少细胞损害。 Another hypothesis suggests that decreased processing of glucose could indicate to cells that food is scarce (even if it isn't) and induce them to shift into an anti-aging mode that emphasizes preservation of the organism over such ‘luxuries' as growth and reproduction. 另一种假设是，葡萄糖代谢的降低相当于在对细胞发出一种食物不足的信号，从而引导细胞切换到一种抗衰老工作模式下，相较于生长或繁殖这类“奢侈活动”这种模式着重的是机体本身的维持。