Life spans in the developed world have doubled over the past two centuries – and each decade we are adding two to three more years. To take the best of this extra time, scientists are working hard to decipher the code of aging.
For thousands of years, the average lifespan of a human being was around 40 years. Evolution holds the explanation: it takes about two decades to grow up and be fully ready to reproduce. Then the offspring come along, and it takes another 20 years to get them ready to leave the nest and repeat the cycle.
“Biologically, we are programmed to live for 40 years, and if we had not been able to do so, the human species would have perished,” explains Rudi Westendorp of the University of Copenhagen, an expert on longevity from a societal point of view.
The improvement in life expectancy over the past two centuries comes from the combined effect of a number of factors. “Sewage systems got better and limited the spread of diseases,” Westendorp explains. “Drinking water became cleaner. The industrial revolution provided more people with paid jobs and more money to spend on food and shelter. Housing got better. We got vaccination programmes and managed to limit the number of children dying. Deaths from violence also dropped dramatically as societies became better at organizing social order and protection.”
According to Westendorp, the importance of medical intervention has been generally overrated when it comes to longevity. “To say that the invention of antibiotics is the reason we’ve expanded our life spans dramatically is false,” he says. “Of course I am not blind to the enormous impact medical care and treatment can have had. There’s no doubt that the decrease in cardiac deaths has significantly contributed to our increased longevity, but there’s no consensus on the contribution of specific factors”.
Two categories of theories
Even if medical discoveries are not the main reason we can now expect to live to 80, they might be why we can live to 80 and still feel, act and look 40. “Researchers in gerontology are generally trying to understand the processes of why and how we age, and trying to manipulate them to treat, stop or even reverse aging,” says Joao Pedro de Magalhaes of the Department of Functional and Comparative Genomics at the University of Liverpool. “But we can’t say that we understand the molecular mechanisms of aging yet.”
A number of theories try to explain why our minds and bodies deteriorate over time. According to De Magalhaes, they can be divided into two categories: damage-based theories and programmed theories. The first consists of those that see aging as a continuous process of DNA damage accumulating inside our bodies and cells due to the environment, to the inefficiency of our internal repair systems or simply as a by-product of normal cellular processes. Programmed theories, on the other hand, consider aging a consequence of genetically regulated processes. In general, though, the theories tend to overlap, and most scientists recognize that genetic regulation cannot be completely separated from DNA damage accumulation and vice versa.
Of mice and men
“Personally, I think that experiments using genetically modified mice have shown that DNA damage accumulation is the most likely culprit when it comes to explaining why we age. But I say that with caution, because we still haven’t seen any conclusive evidence,” explains De Magalhaes. Some of these mice experiments have shown that DNA damage accumulates with age in certain types of stem cells, and research into mice with progeroid syndromes – diseases that cause rapid aging – has shown that these diseases often involve the DNA machinery.
Lars Holm, a physiologist at the Institute of Biomedical Sciences at the University of Copenhagen, agrees. “I’d say it’s pretty well established that the reason we don’t live to 120 is that we are constantly exposed to chemicals, pollution, bad diets, and a lot of other stuff that affects our genome. At one point, our cells lose the ability to regenerate and thereby protect us from all the damaging factors, and that eventually kills us. This process of the body losing its ability to regenerate might very well be the best explanation of what aging is.”
Will the trend continue and if so for how long? For Westendorp the answer is yes; he sees no absolute limits to how old humans can be. “Children born today are likely to become centenarians. There is no biological barrier that must be brought down before we can live to 120, as we have already done, or to 140 or 160.”
Searching for limits
De Magalhaes adds that there is a need for more research into aging itself, as treating the diseases that come with age – like cancer and Alzheimer’s – is only symptomatic. We should aim to treat actual aging if we want to live long and well. “Life spans will continue to increase, but I think there are some limits to how old we can be right now – simply because we age, weaken, and become frail. But if we can understand, tackle and eventually stop that process, there will be no limits. I believe that if we can eradicate viruses, we should be able to eradicate aging as well,” he says.
The University of Copenhagen’s Holm is more sceptical. “I think we can get older, but the thought of eternal life is utopian. I don’t think it’s possible. And even if it was biologically possible, I don’t think the environment would ever make it possible. Our diets, the pollution – we simply can’t avoid the things that damage our system.” So it seems that for now no one can really say how to avoid or reverse the lethal damage to our system that we call aging. But around the world, researchers are developing new ideas, compounds and technologies aimed at increasing life spans and fighting off the side effects of yet another birthday.
Count your calories
One drug that has been thoroughly studied is resveratrol, also known as the red wine drug since the popular beverage is the best source for this compound. Resveratrol has managed to prolong life spans of yeast, worms and mice, though it has struggled to do the same in mammals. Despite that, several labs and companies are still investigating resveratrol, probably because the drug seems to mimic the only proven anti-aging agent out there: caloric restriction, which amounts to simply what it says – eating less than your basic caloric need. “Caloric restriction expands life spans in several species, but we still lack conclusive evidence that it can do the same in humans,” says De Magalhaes. “That said, it is by far the anti-aging intervention that holds the greatest potential, based on our current knowledge.”
Caloric restriction may have to surrender that position now that a drug called rapamycin has wowed scientists worldwide. The drug, used to treat some forms of cancer and to suppress the immune systems of transplant patients, is derived from a species of bacteria found in the soil of Easter Island. It seems able to inhibit some aging processes by putting the brakes on cell growth and enhancing the process of autophagy, a form of cellular recycling. With its significant immunosuppressive abilities, rapamycin is currently too dangerous to be used in anti-aging research on humans, but several companies are trying to develop a copy – called an analogue in pharmaceutical lingo – that has the same effect without the side effects.
Searching for a game changer
“I’m optimistic that we’ll someday have a genuine anti-aging product, and rapamycin might be it,” says De Magalhaes. “It’s capable of extending life in worms, yeast and many different animals like mice, and no other drug has managed that before. If someone can create an analogue, it could be a game changer for aging research.” Søren Brunak, professor of systems biology at the University of Copenhagen, believes that his field can help understand the aging process. “There’s no way you can grasp all the data without using systems biology. The challenge of understanding the interplay between genes, the regulation of genes, the expression of genes, and how the proteins they code for interact with each other is a challenge of grasping systems,” he explains. Systems biology can be described as the next level of bioinformatics. While the latter typically looked at only one type of biological data, for instance DNA, and at only one gene at a time, systems biology aims to integrate many types of biological data.
Even so, Brunak underlines the importance of acknowledging the limitations of systems biology. “Some hope it will enable us to simulate the brain or the physiology of the entire body, but those of us who have been working with this for many years know that this is incredibly difficult, since biological systems are extremely non-linear. It’s like making weather reports a year out into the future, but 19 times harder.” So it seems safe to say that in the field of aging research the best is yet to come. And as we wait for immortality – or at least our 100th birthday – Westendorp has a reminder for us all: “The development of human lifespan is an unprecedented story of success on a societal level, and we need to stop being pessimistic about people becoming older. We will live longer and better than ever, and we should each make it our mission to make the most of it.”
By Line Emilie Fedders @LineFedders