第1自然段

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. 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. Those findings suggest that caloric restriction could delay aging and increase longevity in humans, too.

最近，关于衰老的研究人员指出，目前市场上没有任何一种治疗方法被证明可以减缓人类衰老的进程，即分子和细胞损伤的积累，这会增加我们在变老过程中患病的脆弱性。但是，一种干预方法，即摄入低热量但营养平衡的饮食，在广泛的动物范围内表现出非常好的效果，可以延长寿命并延缓健康状况的恶化。这些发现表明，限制热量摄入可能也可以延缓人类的衰老过程，延长寿命。

第2自然段

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. Few mortals could stick to that harsh a regimen, especially for years on end. But what if someone could create a pill that mimicked the physiological effects of eating less without actually forcing people to eat less? 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? 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. 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.

然而，为了获得最大的益处，人们可能需要将热量摄入量减少约30%，相当于从每天2500卡路里减少到1750卡路里。很少有人能坚持这样严格的饮食规定，尤其是长期如此。但是，如果有人可以创造一种模拟少吃食物的药丸而不需要实际减少食物摄入量，那会怎么样呢？这种我们称之为“模拟限制热量摄入”的药丸能否让人们延缓衰老，延长健康的年龄，将与年龄相关的疾病（如糖尿病、动脉硬化、心脏病和癌症）推迟到生命的最后阶段？科学家在20世纪90年代中期首次提出了这个问题，当时研究人员发现一种化学物质在啮齿动物身上似乎具有限制热量摄入的许多好处。尽管目前尚未找到一种能够安全实现相同效果的化合物，但这项研究具有启发作用，并使人们对限制热量摄入模拟物的开发抱有希望。

第3自然段

The hunt for CR mimetics grew out of a desire to better understand caloric restriction’s many effects on the body. 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. 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. 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.

对限制热量摄入模拟物的追求源于人们对限制热量摄入对身体的许多影响的进一步了解的愿望。科学家在60多年前首次认识到这种实践的价值，当时他们发现，与自由饮食的老鼠相比，饮食低热量的老鼠平均寿命更长，而且老年常见的疾病发生率也降低了。更重要的是，一些受治疗的动物的寿命超过了对照组中最长寿命的动物，这意味着最大寿命（最长可达到的年龄），而不仅仅是正常寿命，也增加了。各种干预措施，如抗感染药物，可以增加群体的平均存活时间，但只有能减缓身体衰老速度的方法才能延长最大寿命。

第4自然段

The rat findings have been replicated many times and extended to creatures ranging from yeast to fruit flies, worms, fish, spiders, mice and hamsters. Until fairly recently, the studies were limited to short-lived creatures genetically distant from humans. 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.

老鼠的研究结果已经多次复制，并扩展到从酵母到果蝇、蠕虫、鱼类、蜘蛛、小鼠和仓鼠等各种生物。直到最近，这些研究还局限于与人类基因差异较大的寿命较短的生物。但是在与人类更密切相关的两个物种——恒河猴和松鼠猴上进行的限制热量摄入项目让科学家对限制热量摄入模拟物对人类可能具有帮助持乐观态度。

第5自然段

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.

这些恒河猴和松鼠猴的项目表明，与正常进食的对照动物相比，限制热量摄入的猴子体温和胰岛素水平较低，并且保持了一些随年龄增长而下降的激素年轻水平。

第6自然段

The caloric-restricted animals also look better on indicators of risk for age-related diseases. 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). 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. 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. Unlike the multitude of elixirs being touted as the latest anti-aging cure, CR mimetics would alter fundamental processes that underlie aging. We aim to develop compounds that fool cells into activating maintenance and repair.

限制热量摄入的动物在与年龄相关疾病的风险指标方面也表现得更好。例如，他们的血压和甘油三酯水平较低（表示心脏病发生几率降低），他们的血糖水平更接近正常（指示糖尿病的风险降低，糖尿病以异常高的血糖水平为特征）。此外，最近的研究还表明，长期进行限制热量摄入饮食的恒河猴（近15年）患慢性病的情况较少。然而，这些猴子和其他猴子仍需跟踪观察更长的时间，才能知道低热量摄入是否能够增加猴子的平均和最大寿命。与大量宣传成为最新抗衰老良药的万能灵丹不同，限制热量摄入模拟物将改变衰老的基本过程。我们的目标是开发出一种可以欺骗细胞激活维修和修复的化合物。

第7自然段

The best-studied candidate for a caloric-restriction mimetic, 2DG (2-deoxy-D-glucose), works by interfering with the way cells process glucose. It has proved toxic at some doses in animals and so cannot be used in humans. But it has demonstrated that chemicals can replicate the effects of caloric restriction; the trick is finding the right one.

最受关注的限制热量摄入模拟物候选者是2DG（2-脱氧-D-葡萄糖）。它通过干扰细胞处理葡萄糖的方式发挥作用。在动物身上，某些剂量2DG已被证明具有毒性，因此不能用于人类。但它已经证明了化学物质可以复制限制热量摄入的效果，关键是找到正确的化合物。

第8自然段

Cells use the glucose from food to generate ATP (adenosine triphosphate), the molecule that powers many activities in the body. By limiting food intake, caloric restriction minimizes the amount of glucose entering cells and decreases ATP generation. 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. Researchers have proposed several explanations for why interruption of glucose processing and ATP production might retard aging. 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. Reduced operation of the machinery should limit their production and thereby constrain the damage. 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.