Text: Clément Bürge
Photo: Illustration: Leha van Kommer

The quest for immortality

A growing number of research projects are looking for ways to extend lifespan. Tests on human beings are set to launch shortly.

The science of immortality has always captivated researchers. In 1914, the French surgeon Serge Voronoff tried to extend life expectancy by grafting monkey glands into humans. In more recent years, research on methods to stop – or at least slow – ageing has been rejuvenated. In 2013, Google founded Calico, a company aimed at finding a cure for ageing. Another example is Dmitry Itskov, a Russian multi-millionaire who has brought together researchers from around the world to develop a solution to immortality. “The number of projects is increasing for one simple reason: we are getting closer to the end goal,” says Aubrey de Grey, an immortality specialist. He believes that, for the first time in the history of humanity, we have the fundamental knowledge needed to prolong life expectancy. Now it is just a question of time. Here we present an overview of the most compelling projects.

1 Rejuvenating the hearts of mice

Amy Wagers and Richard T. Lee, researchers from the Harvard Stem Cell Institute (USA), surgically connected the circulatory system of a young mouse to that of an older mouse. After only four weeks, the symptoms of cardiac hypertrophy due to the older rodent’s ageing had reversed. “The heart’s walls thicken with age in mice, as they do in humans,” says Richard T. Lee. “This is the primary cause of age-related heart failure. In our experiments, the older mouse’s heart had clearly regained the size of the younger mouse’s. It was visible to the naked eye.” The researchers also noticed that this rejuvenation was caused by the presence of a blood protein, GDF-11. They are now trying to establish what effects the protein could have on other types of tissue. “We hope to begin clinical trials within four to five years.”

2 The paradox of natural selection

Natural selection favours organisms that have the best chances of survival and reproduction. Based on this logic, the process should prevent genes that trigger ageing from being passed on. But that is not the case. British researcher John Pannell, professor in the Department of Ecology and Evolution at the University of Lausanne, wanted to understand why. He studied the longevity of the “Silene latifolia” plant. “It’s a paradox. Ageing and the deterioration of the organism decrease survival and reproductive performance,” he says. His team led an experimental study on quantitative genetic models. “We discovered that organisms do not develop genetic mutations at the beginning of their lives because they have greater chances of reproduction,” the scientist explains. “However, as they age, the reproductive performance in these organisms declines. That’s when they develop signs of senescence.” The genes that cause ageing are then passed on from generation to generation for one important reason. We might expect natural selection to eliminate these genes, he says, but they offer a set of advantages, mostly reproductive, which it is difficult to do without. His findings offer insight about how ageing functions and increases the chances of developing a treatment.

3 The seven causes of ageing

British researcher Aubrey de Grey has become a key figure in the fight against ageing. With his long bushy beard, pale skin and elongated silhouette, the University of Cambridge (UK) educated software engineer turned self-taught expert in biogerontology resembles a character worthy of a Shakespearian play. He has identified seven types of ageing damage. These include cells that die and cannot be replaced, cells that should die but continue to live, mutations in the nuclear and mitochondrial DNA and junk aggregates inside and outside cells. To address these seven points, Aubrey de Grey founded the United States-based research foundation SENS – Strategies for Engineered Negligible Senescence. “We fund regenerative medicine projects and lead a number of them,” says de Grey. “Our goal is to prevent age-related illnesses.” Aubrey de Grey is convinced that the first man to live one thousand years is already alive. He gives it a 30% to 40% chance that the people in his age bracket – in their forties – are young enough to benefit from these therapies.

4 Reproduction, the key to longevity?

Research by Hugo Aguilaniu from the école Normale Supérieure de Lyon (France) is based on an observation that during reproduction animal organisms rejuvenate radically. “When a child is conceived, cells that are several decades older – those of the parents – combine to create cells that are age zero,” says Hugo Aguilaniu. “I wanted to understand how that worked.” The French researcher used a nematode worm, Caenorhabditis elegans, as a model and discovered that the oxidation of its oocytes slowed considerably during reproduction. “Once the process is revealed, we can identify the genes and proteins that can slow ageing in humans.” Hugo Aguilaniu also applies another approach. “We analyse the impact of some genes that potentially increase the organism’s longevity.” There are thought to be about fifty of them that notably boost stress resistance. “The problem is that if we activate them, we risk jeopardising the human’s reproductive abilities.” The researcher has already filed patents on some genes, such as nhr-80. “We are continuing our work, but we are still several years away from beginning experiments on humans.”

5 The promises of the immortal jellyfish

In 1988, a young German researcher named Christian Sommer discovered the Turritopsis dohrnii jellyfish off the Italian coast while conducting research on hydrozoans. He noticed that the little creatures did not die. In 1996, a team of researchers observed that the jellyfish can revert to polyp form, the earliest stage of life, at any time. As such, this gelatinous being can “escape death” and become immortal. The transformation is comparable to a chicken becoming an egg, then a chick again. The discovery drew the attention of a Japanese researcher, Shin Kubota, who is convinced that this jellyfish holds the key to longevity in humans. He has published more than fifty scientific articles on these animals and how they work, but has not yet unlocked the secret to their immortality.

6 A molecule for living longer

Rafael de Cabo works for the National Institute on Aging, a US government-led organisation formed by Congress in 1974 to study life extension. The institute discovered that the activation of the protein sirtuin 1 delayed the onset of age-related diseases. “We used a small molecule called SIRT1720 on mice to increase their sirtuin 1 level,” says the Spanish-born researcher. He gave a 100-mg dose of SRT1720 to mice from age six months to the end of their life. De Cabo found that the mice’s life expectancy increased 8.8%, and their muscular function improved. At the same time, their weight and the proportion of fat in their body fell. “Our research illustrates that we can develop molecules that ameliorate the burden of metabolic and chronic diseases associated with ageing.” The National Institute of Aging plans to launch clinical tests on sirtuin 1 activators in 2014.



​Keeping things under control

Regulating production

The development of medication to treat ageing may be a sensitive subject for the pharmaceutical industry. “The treatments that will be developed will primarily be preventive,” says Hugo Aguilaniu. “The pharmaceutical industry can theoretically sell an infinite number of drugs. But how far will it go? I fear that those companies are not capable of setting reasonable limits.” These drugs could potentially generate almost infinite revenue. “External regulation would be necessary,” says the longevity expert. Another obstacle is that, to prove that these drugs increase lifespan, clinical trials would have to be conducted for 50 years. “And no company has the means to do that.”

Preventing social repercussions

Every human has to die someday. Certain people believe that artificially extending human life is unnatural. “Some think a distinction should be made between ageing and age-related diseases, which is absurd,” says Aubrey de Grey. “We are trying to slow the accumulation of junk in our bodies to cure diseases caused by ageing. It’s merely preventive medicine.” Extending life expectancy will also present a huge challenge for society. “The social repercussions will be dramatic,” says Rafael de Cabo. “How can we take care of people who live to age 120 or 150? How can we pay for their care? It would require major social reforms.” The Japanese researcher Shin Kubota also believes that the demographic growth would be unmanageable.