Slowing human aging is now the subject of serious research

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(Graphic: The Economist)

Things have improved since Good Queen Bess’ reign. People in the rich world can now reasonably expect that the days of their years will last well beyond seventy. Those in poorer countries are catching up (see Chart 1). Since 1950, average life expectancy around the world has increased by 18 weeks every year.

However, there are two catches. One of these is that the increases seem to have a limit. The number of centenarians has grown and will continue to increase. The Pew Research Center predicts that there will be 3.7 million people worldwide by 2050, three times as many per capita as in 2015. But only one in a thousand of them live past the age of 110, and none in history has been reliably proven to be older than 120 years. The average is going up; the maximum, much less (see graph 2). The other problem is that the ‘health span’, the number of healthy, vital years, does not automatically keep pace with lifespan.

Some of Elizabeth’s modern equivalents in wealth, if not majesty, are as desperate as she was for more moments than are currently on offer. In the hope of a longer and healthier life, they offer substantial deposits to today’s alchemists, the wizards of medicine and biotechnology who seek to understand, slow down and, ideally, prevent the aging of the body and its attendant ailments. turn.

Peter Thiel, co-founder of PayPal, Larry Page and Sergey Brin, co-founders of Google, and Jeff Bezos, founder of Amazon, have all invested in, and often been instrumental in creating, companies that seek to extend the lifespan extend your health span. In March, Sam Altman, the head of OpenAI, revealed that two years ago he had invested $180 million in Retro Biosciences, a Silicon Valley company founded with the aim of extending the lifespan of healthy people by ten years.

Under the canopy of companies backed by tech royalties, an undergrowth of more conventionally funded startups is working on drugs that could slow or delay some aspects of aging. Even closer to the ground, the idea of prolonging life and health using pills and potions that are already available is beginning to catch on, in addition to (and sometimes instead of) the conventional approach of diet, exercise and early bedtime. . A culture of do-it-yourself lifespan extension is emerging, at least in affluent areas endowed with the kind of technical expertise and technological hubris that characterize Silicon Valley.

Many in mainstream science and medicine view this somewhat askance. That is understandable. It’s an area that attracts chancers and charlatans, as well as those with more decent motives, and its history is littered with “breakthroughs” that have gone more or less nowhere. The US Food and Drug Administration does not recognize ‘old age’ as a disease condition, and therefore as an appropriate target for therapy. Nevertheless, evidence is mounting that such research may have something to offer.

Some established drugs actually appear to extend life, at least in mice. This offers both the possibility that they can do this in humans and some insight into the processes involved. The increasing ease with which genes can be edited is aiding such studies, as is access to large amounts of gene sequence data. The ability to produce personalized stem cells, which remain young forever, has opened up new therapeutic possibilities. And new diagnostic tools now provide scientists with means to calculate the “biological ages” of bodies and organs and compare them to actual calendar ages. In principle, this allows longevity research to achieve conclusive results in less than a human lifetime.

The machine stops

Aging seems quite simple. Bodies are machines, and machines wear out. But unlike most machines, bodies make and repair themselves. Why don’t they do it perfectly?

One answer is that the designer of the machines, evolution, is interested in reproduction, not longevity. Life is a matter of genes and environment, and the environment, in the form of accidents, predators and diseases, is what kills most creatures. Genes with benefits that only emerge over a longer lifespan than the environment allows are unlikely to do particularly well unless they provide other benefits. Genes that provide a successful and fruitful childhood are on the way to a winner.

Evolution would indeed be actively conspiring against old age. If a gene helps a young animal breed but endangers it when it is old, it is likely to spread. There is evidence that one variant of a particular gene involved in Alzheimer’s disease provides reproductive benefits for young people.

. generally, from the evolutionary point of view of the genes involved, an individual is simply a means of making further copies of those genes, and not an end in itself. Keeping the body’s repair mechanisms in top condition is only worth it if more genes make it into the next generation. If other uses of these resources do the job better, repair will lose out. In this ‘disposable soma’ approach, the individual is a means to an end that is abandoned when it is no longer fit for purpose.

This kind of perspective explains why there are many conditions, such as Alzheimer’s and Parkinson’s diseases, retinal degeneration, type 2 diabetes, and several forms of cancer, that are rare in early life but quite common in old age. But it also suggests that this need not be the case. The fact that evolution has no interest in keeping the repair systems running doesn’t mean this isn’t possible, just that some cunning may be required.

Most genes have variants, known as alleles, which all work but can have slightly different effects. Genetic engineering of laboratory organisms and research into the genes of human centenarians have identified alleles of certain genes that have been experimentally proven to extend lifespan in the first case and are associated with longer lives in the second. Such work helps alleviate the processes behind physical aging.

For example, it could lead to insights into why, as a study published in 2014 by researchers at King’s College London found, centenarians are less likely to die from cancer or heart disease than people in their 80s. This suggests that people who live very long lives can do this because they have a relatively rare form of protection against things that kill younger, old people. That could be very good news.

However, there is still something killing them. The King’s College research found that centenarians are disproportionately vulnerable to general weakness and pneumonia, the old man’s friend.

Another reason for hope despite the insensitivity of evolution is that the physiological details of aging are becoming increasingly clear. In particular, those who have explored this issue have managed to break the problem down into bite-sized chunks that can, to some extent, be addressed individually. Some of these smaller (though often still huge) problems are themselves attractive targets for intervention; chronic inflammation, for example, or the accumulation of abnormal proteins that occur in Alzheimer’s disease. George Church of Harvard University, a biotech guru unafraid of the unorthodox, thinks the approach can do more than that: identify and treat each of the components separately and you’ll find you’ve solved the problem in its entirety.

Several groups have compiled lists of such chunks. One of the most consulted was devised by Carlos López-Otín of the University of Oviedo, in Spain, and his colleagues. They propose 12 hallmarks of aging (see chart), chosen on the basis that they are all things that tend to get worse with age, that accelerate aging if stimulated, and that appear to slow aging if treated. Tackle this dirty dozen (Dr. Church would make it a baker’s dozen by adding cancer to the role) and you could extend life indefinitely and healthily. At least that’s how the optimists look at it.

Oncology is already a well-developed field of research. This report does not address this directly. Also, no commentary will be made on diet, exercise and a good night’s sleep, except to extol their value. They remain as necessary as ever.

Instead, it will look at progress being made on each of the twelve characteristics. The resulting image is not as neat as you would like. Biology is a complex, networked affair and many features of aging overlap. Sometimes this means that an intervention can be good in more than one area. At other times there may be trade-offs. But even covering part of the list will give people a better life. Deal with it all and, well, who knows?