Fight Aging!

A brace of popular science articles on aging research were recently published at the Economist. Like many of these views from a distance written by journalists on the outside, peering into the field, one must assume that its existence is largely the result of the sizable investments made over the last two years into the development of therapies based on partial reprogramming. The Altos Labs funding in particular represented a meaningful fraction of all investment into biotech made that year. That tends to attract attention. From there, an investigator would notice an additional broad focus on cellular senescence, many companies and research groups working towards the development of senolytic therapies to clear senescent cells from aged tissues.

After that, however, there are few obvious high points for the outside observer to focus on. Epigenetic clocks, perhaps. The relentless self-promoters such as David Sinclair. But it quickly starts to become harder to figure out what is going on, which of the hundreds of small biotech companies and research groups in the field, trying to treat age-related disease by focusing on mechanisms of aging, are important. It is certainly the case that theories of aging abound, and researchers disagree on which paths are best. A sizable fraction of the progress of the next twenty years in the matter of treating aging as a medical condition will arise not because of the where the mainstream is focused, but will occur because a few small biotech companies tried something and it turned out to be far more useful than most of the community expected it to be.

There are advantages and disadvantages to the way in which distribution of funding tends to follow a power law. The projects at the top of the list, such as partial reprogramming, will definitely have enough funds to determine whether or not these are good approaches to rejuvenation. If they fail, then on to the next. Something will be accomplished, one way or another. But aging is a complex process of many different mechanisms, and many different approaches to therapy will be needed, not just one. Exploring the potential of the rest of the projects, underneath those at the top of the list, is just as necessary in the long run.

In search of forever

Slowing, let alone reversing, the process of ageing was once alchemical fantasy. Now it is a subject of serious research and investment. Peter Thiel, a 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 the creation of, firms trying to prolong lifespan and healthspan. In March Sam Altman, the head of OpenAI, revealed that two years ago he had invested $180m in Retro Biosciences, a Silicon Valley firm founded with the goal of adding ten years to healthy human lifespans.

Beneath the forest canopy of firms backed by tech royalty an undergrowth of more conventionally financed startups is working on drugs that might slow or stall some aspects of ageing. Even closer to the ground, the idea is catching on of prolonging lifespan and healthspan using pills and potions that are already available, in addition to (and sometimes instead of) the conventional approach of diet, exercise, and early-to-bed. A culture of do-it-yourself lifespan extension is emerging, at least in affluent places endowed with the sort of technical expertise and technological hubris identified with Silicon Valley.

Many in mainstream science and medicine look at all this slightly askance. That is understandable. It is an area which attracts chancers and charlatans as well as those with more decent motives, and its history is littered with "breakthroughs" that have led more or less nowhere. America's Food and Drug Administration does not recognise "old age" as a disease state, and thus as a suitable target for therapy. Nevertheless, evidence has been accumulating that such research might have something to offer.

Some established drugs really do seem to extend life, at least in mice. That offers both the possibility that they might do so in people and some insight into the processes involved. The ever-greater ease with which genes can be edited helps such investigations, as does access to large amounts of gene-sequence data. The ability to produce personalised stem cells, which stay forever young, has opened up new therapeutic options. And new diagnostic tools are now offering scientists means to calculate the "biological ages" of bodies and organs and compare them with actual calendar ages. In principle this allows longevity studies to achieve convincing results in less than a lifetime.

Another reason for hope is that the physiological details of ageing are becoming clearer. In particular, those researching the question have been able to divide the problem into bite-sized chunks that can, to some extent, be tackled individually. Researchers have proposed 12 hallmarks of ageing chosen on the basis that they are all things which typically get worse with age, which accelerate ageing if stimulated and which seem to slow it down if treated. Some of these smaller (if often still huge) problems are attractive targets for intervention in their own right; chronic inflammation, for example, or the build-up of aberrant proteins seen in Alzheimer's disease. George Church of Harvard University, a biotech guru unafraid of the unorthodox, thinks the approach could offer more than that: identify and deal with each of the components separately and you may find you have solved the problem in its entirety.