The ambitious quest to cure ageing like a disease
The list of diseases humankind has managed to defeat is impressive – polio, typhoid, measles, tetanus, yellow fever, smallpox, diphtheria and chicken pox have been almost completely eliminated in many parts of the world. Vaccines and powerful drugs have allowed our species to fight back against the bacteria, parasites and viruses that threaten to kill us.
But throughout history, humans have suffered from a condition that they have never been able to escape – ageing. As we get older, our cells stop working as well and can break down, leading to conditions like cancer, heart disease, arthritis and Alzheimer’s disease. Together, ageing-related diseases are responsible for 100,000 deaths per day and billions are spent around the world trying to slow their steady march on our bodies.
Some researchers, however, believe we may be thinking about these conditions in the wrong way. They say we should start treating ageing itself as a disease – one that can be prevented and treated. In a recent episode of the BBC Tomorrow’s World podcast, my fellow presenter Ellie Cosgrave and I spoke to some of those who are investigating ways to slow and even halt the ageing process.
不过，有研究人员认为我们对衰老的看法可能是错误的。他们表示，我们应开始把衰老本身视为一种疾病——它是可以被阻止和治疗的。在BBC Tomorrow的最新一集World播客中，埃莉·科斯格雷夫（Ellie Cosgrave）和我一起与一些正在探究延缓、甚至阻止衰老过程方法的研究人员对话。
Their hopes are founded on recent discoveries that suggest biological ageing may be entirely preventable and treatable. From a biological perspective, the body ages at different rates according to genetic and environmental factors. Tiny errors build up in our DNA and our cells begin developing faults that can accumulate into tissue damage. The extent of these changes over time can mean the difference between a healthy old age or one spent housebound and afflicted by chronic diseases.
The scientists who hope to do this sit on the fringes of the mainstream medical landscape. But there are now a number of research centres around the world that have made identifying ways of preventing biological ageing a priority. Studies in animals have shown that it is indeed possible to dramatically extend the lifespan of certain species, giving hope that it could also be possible in humans.
One common diabetes drug, metformin, was able to extend the lifespan of rodents. In the early 1990s, Cynthia Kenyon, now vice president of ageing research at Calico Labs, the Google-backed anti-ageing research company, demonstrated that roundworms could live six weeks instead of their natural three just by changing a single letter of their genetic code.
一种平常的糖尿病药物二甲双胍能够延长啮齿类动物的寿命。20世纪90年代初，谷歌支持的抗衰老研究公司Calico Labs的副总裁辛西娅·凯尼恩（Cynthia Kenyon）曾演示过，只需通过修改蛔虫基因密码中的一个字母，它的寿命就可以从自然的三周延长到六周。
In our Tomorrow’s World podcast episode about ageing, one of the leading figures in human longevity research, Aubrey De Grey, tells us how similar increases in lifespan could be achieved in humans. De Grey is the chief science officer at the Strategies for Engineered Negligible Senescence (Sens) Research Foundation, a California-based regenerative medicine research foundation focused on extending the healthy human lifespan. He explains their goal is to develop a suite of therapies for middle-aged and older people that will leave them physically and mentally equivalent to someone under the age of 30. “Of course, without wiping their memories,” he adds.
在Tomorrow's World播客关于衰老的一集中，人类寿命研究领域的领袖人物奥布里·德·格雷（Aubrey De Grey）告诉我们人类也可以通过类似的方法延长寿命。他是美国可忽略衰老研究工程战略基金会（Strategies for Engineered Negligible Senescence (Sens) Research Foundation）的首席科技官。这是加州的一家再生医药研究基金会，专注于延长人类的健康寿命。他解释说，他们的目标是为中年人和老年人开发一套疗法，让他们重新成为在生理和心理上不到30岁的人。"当然，我们不会消除他们的记忆，"他补充说。
De Grey says they want “to fix the things we don’t like about the changes that happen between the age of 30 and the age of 70”. There are seven biological factors De Grey argues are predominantly responsible for cellular damage that accompanies ageing and underlies ageing-related diseases.
These include when cells in a tissue are not renewed quickly enough; when cells replicate uncontrollably as occurs in cancer; when cells don’t die when they should, which is another problem in cancer; damage to the DNA of the tiny power plants found in cells, known as mitochondria; the accumulation of waste products inside the cell; waste products that build up outside cells; and the stiffening of the lattice structure outside of cells, called the extra-cellular matrix, which allows tissues to stretch and bend.<纽约时报中英文网 http://www.qqenglish.com/>
De Grey and his team at the Sens Research Foundation say they have identified ways for each of these problems to be combatted with therapies they’re developing.
“The fix for the first (problem) of having too few cells is stem cell therapy,” says De Grey. This provides tissue with a fresh supply of young cells to replace those that die during ageing. Other issues, such as when cells don’t die when they are supposed to, may require more complex solutions.
“In principle, we could use gene targeting to introduce suicide genes – genes which the cells will express that will make proteins that will simply kill the cell,” says De Grey. The trick here, however, will be engineering the genes in such a way that they will only express the lethal protein if the cell’s growth patterns are doing more bad than good.
De Grey doesn’t think that it will be possible stop ageing altogether with these types of approaches, but they may give patients an extra 30 years or so of life. He envisages a future where “rejuvenation technologies” can be administered to old people in order to revert their cells to what they were like when they were in their youth, buying them extra time. The idea is that someone who is treated at the age of 60 will be biologically reverted to 30. But because the therapies are not permanent fixes, their cells will end up becoming 60 years old again in another 30 years time.
By then De Grey hopes the therapies could be reapplied as “version 2.0” to revert the same individuals once again to become younger in their cells. As a result, that person’s cells wouldn’t become 60 again until they’re about 150 years old.
But, there needs to be some caution when dealing with claims like this. There is no experimental evidence to show that our bodies would respond to this sort of “software update”. Much like computers, with too many updates our bodies could grind to a halt.
But De Grey believes this kind of thinking, something he calls “the pro-ageing trance”, is holding back the advance of anti-ageing technologies. The problem, he says, is that we culturally accept ageing as unavoidable and so attempts to halt the damage it causes are often dismissed as quack science.
And he is not alone in believing ageing-related diseases can be solved. George Church, a geneticist at Harvard Medical School, told us that while some of his colleagues argue many age-related diseases are so complex that they simply can’t be treated, he finds such thinking to be incorrect.
“If you can control both the environment and the genetics, you can get people that live youthful healthy lives for exceptionally much longer than others,” says Church. “In industrialised nations, most of the diseases are due to age-related diseases and I think those too can be handled.”
Among the prominent approaches to increasing longevity is a gruesome-sounding procedure that is commonly known as “vampire therapy”. Dementia patients who were given transfusions of blood plasma from younger donors aged between 18 and 30 years old showed signs of improvement in a recent trial. Patient’s with early-onset Alzheimer’s disease regained the ability to bathe or dress themselves, or to do other tasks such as housework.
While this trial is still ongoing, one US start-up called Ambrosia is already offering older customers the chance to receive transfusions of blood from donors aged between 16 and 25 years old for $8,000 (£5,985) per treatment. The company says that these transfusions can boost the performance of older people’s lethargic cells, and also claims to have improved the condition of an early-onset Alzheimer’s patient as well as have turned the hair of a 60-something-year-old patient darker. Their research, however, has yet to be published in any peer-reviewed journals and has been criticised for not accounting for the placebo effect.
But there are some studies in animals that suggest there may be a biological basis for the effects these treatments are having. In 2013, a study by researchers at the Harvard Stem Cell Institute showed the muscle strength of mice could be improved by a growth factor found in young blood called GDF11, though the findings could not be replicated. BBC Future has previously explored some of the other approaches in animals that could lead to a longer life. Meanwhile, others say the key to longevity is as simple as cutting the amount of calories you consume in a day.
But what about actually “curing” death? There have long been proposals to do this by cryogenically freezing a person’s brain or body immediately after death so they can be revived at a later date when technology has advanced sufficiently. A number of companies even offer the opportunity for wealthy clients to preserve their bodies in this way, such the Alcor Life Extension Foundation. However, to date, none of their clients have ever been resurrected from their icy storage units.
但是什么能真正"治愈"死亡？很早以前就有人提出在人刚刚死亡时冷冻大脑或者身体，这样就可以等待日后技术足够进步以后再重生。一些公司甚至为富有的客户提供冷冻保存身体的机会，比如阿尔科生命延续基金（Alcor Life Extension Foundation）。然而，到目前为止，还没有任何客户从冷冻储藏单元中被复活。
Others, such as Ray Kurzweil, theorist of the Singularity and lead engineer at Google have espoused “mind uploading” as a way to achieve (at least digital) immortality.
It’s easy to conflate these outlandish ideas, which seem more based in science fiction than reality, with the lab-based work De Grey and others in longevity research are doing. But regardless of how it is achieved, extending human lifespans by decades or even hundreds of years will present us with some difficult social realities. As BBC Future has explored before, there could be major societal impacts if we all start living longer. There are some that fear greater longevity could lead to swelling populations and raise doubts that our planet could support such numbers.
De Grey himself says he is often asked about whether the technologies he is working on could be abused by wealthy tyrants to give them extended lifespans, while others ask whether we will simply be bored by lives that can be continuously extended.
He has little time for such questions and believes that other technologies – such as artificial meat, desalination, solar energy and other renewables – will increase the carrying capacity of the planet, allowing more people to live longer lives. But this rationale suffers from a dependence on uncertain techno-fixes that may not alleviate suffering in an equally distributed manner.
Yet, if concerns like these had paralysed the early pioneers of vaccination and antibiotics, it is unlikely many of us today could expect to live much beyond the age of 40-years-old. Advances in medicine over the last two centuries have taught us that we have the power to defeat the diseases that afflict us. Perhaps if we apply ourselves, then we can beat ageing too.