BIOLOGISTS have made a lot of progress in understanding ageing. They have not, however, been able to do much about slowing it down. Particular versions of certain genes have been shown to prolong life, but that is no help to those who do not have them. A piece of work reported in this week's Nature by Darren Baker of the Mayo Clinic, in Minnesota, though, describes an extraordinary result that points to a way the process might be ameliorated. Dr Baker has shown—in mice, at least—that ageing body cells not only suffer themselves, but also have adverse effects on otherwise healthy cells around them. More significantly, he has shown that if such ageing cells are selectively destroyed, these adverse effects go away.

The story starts with an observation, made a few years ago, that senescent cells often produce a molecule called P16INK4A. Most body cells have an upper limit on the number of times they can divide—and thus multiply in number. P16INK4A is part of the control mechanism that brings cell division to a halt when this limit is reached.

The Hayflick limit, as the upper bound is known (after Leonard Hayflick, the biologist who discovered it), is believed to be an anticancer mechanism. It provides a backstop that prevents a runaway cell line from reproducing indefinitely, and thus becoming a tumour. The limit varies from species to species—in humans, it is about 60 divisions—and its size is correlated with the lifespan of the animal concerned. Hayflick-limited cells thus accumulate as an animal ages, and many biologists believe they are one of the things which control maximum lifespan. Dr Baker's experiment suggests this is correct.

Age shall not weary them

Dr Baker genetically engineered a group of mice that were already quite unusual. They had a condition called progeria, meaning that they aged much more rapidly than normal mice. (A few unfortunate humans suffer from a similar condition.) The extra tweak he added to the DNA of these mice was a way of killing cells that produce P16INK4A. He did this by inserting into the animals' DNA, near the gene for P16INK4A, a second gene that was, because of this proximity, controlled by the same genetic switch. This second gene, activated whenever the gene for P16INK4A was active, produced a protein that was harmless in itself, but which could be made deadly by the presence of a particular drug. Giving a mouse this drug, then, would kill cells which had reached their Hayflick limits while leaving other cells untouched. Dr Baker raised his mice, administered the drug, and watched.

The results were spectacular. Mice given the drug every three days from birth suffered far less age-related body-wasting than those which were not. They lost less fatty tissue. Their muscles remained plump (and effective, too, according to treadmill tests). And they did not suffer cataracts of the eye. They did, though, continue to experience age-related problems in tissues that do not produce P16INK4A as they get old. In particular, their hearts and blood vessels aged normally (or, rather, what passes for normally in mice with progeria). For that reason, since heart failure is the main cause of death in such mice, their lifespans were not extended.

The drug, Dr Baker found, produced some benefit even if it was administered to a mouse only later in life. Though it could not clear cataracts that had already formed, it partly reversed muscle-wasting and fatty-tissue loss. Such mice were thus healthier than their untreated confrères.

Analysis of tissue from mice killed during the course of the experiment showed that the drug was having its intended effect. Cells producing P16INK4A were killed and cleared away as they appeared. Dr Baker's results therefore support the previously untested hypothesis that not only do cells which are at the Hayflick limit stop working well themselves, they also have malign effects (presumably through chemicals they secrete) on their otherwise healthy neighbours.

Regardless of the biochemical details, the most intriguing thing Dr Baker's result provides is a new way of thinking about how to slow the process of ageing—and one that works with the grain of nature, rather than against it. Existing lines of inquiry into prolonging lifespan are based either on removing the Hayflick limit, which would have all sorts of untoward consequences, or suppressing production of the oxidative chemicals that are believed to cause much of the cellular damage which is bracketed together and labelled as senescence. But these chemicals are a by-product of the metabolic activity that powers the body. If 4 billion years of natural selection have not dealt with them it suggests that suppressing them may have worse consequences than not suppressing them.

By contrast, actually eliminating senescent cells may be a logical extension of the process of shutting them down (they certainly cannot cause cancer if they are dead), and thus may not have adverse consequences. It is not an elixir of life, for eventually the body will run out of cells, as more and more of them reach their Hayflick limits. But it could be a way of providing a healthier and more robust old age than people currently enjoy.

Genetically engineering people in the way that Dr Baker engineered his mice is obviously out of the question for the foreseeable future. But if some other means of clearing cells rich in P16INK4A from the body could be found, it might have the desired effect. The wasting and weakening of the tissues that accompanies senescence would be a thing of the past, and old age could then truly become ripe.