Science is closing in on the frailties of old age
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Do you fancy becoming immortal? Me neither. Silicon Valley titans who lust after “escape velocity from death” leave me cold. But most of us would love to stay younger for longer — preferably without Botox. A stream of breakthroughs suggests that the science of ageing is now at an inflection point.
Already, our perceptions of old age are changing. People who packed out concert halls in their youth to hear the Beatles sing “will you still need me . . . when I’m 64?” now think that old age starts at 74. According to a big German study, those in middle or older age today have an elevated idea of “old” compared to previous generations.
This mirrors increases in life expectancy, especially for the better-off half of the population in rich countries. The big prize now is to improve the final decade for everyone — rich and poor. Few of us want to live forever, even if it was on offer; but we’d give a great deal to avoid a grim descent into the twilight zone of crippling frailty.
Ever since I interviewed scientists for a book about ageing, I am regularly asked for my advice on what substances to take, including “off-label”. Everyone wants a longevity short-cut. American men in high-powered jobs are especially keen to experiment with products, including supplements, which are available in the US not Europe. I myself am taking one of them, with no visible results — but then they wouldn’t be visible. Given the amount of snake-oil in this market, it’s safer to wait for formally licensed products. But that is now the big question: will regulators agree to consider ageing as a “treatable” condition?
While conventional medicine treats one disease at a time, scientists since the 1990s have been making discoveries that suggest we could target the biology that underlies ageing itself. They have created worms and mice that live longer, and stay vibrant for longer, by targeting particular genes. Cynthia Kenyon, the biologist who found that partially disabling a single gene could double the lifespan of roundworms, described to me the awe she felt watching the modified worms wiggling around almost until death, skipping the prolonged doddery stage she observed in their normal worm friends.
A steady flow of discoveries is driving the emerging field of geroscience. Many focus on stemming the decline in the body’s ability to repair DNA. Some molecular biologists are working on NAD (nicotinamide adenine dinucleotide), an enzyme central to metabolism that declines as we get older. Others, like the Australian-American David Sinclair believe that epigenetic noise is a major cause of ageing, confusing signals in the body. Sinclair and colleagues at Life Biosciences have partially restored sight to mice and monkeys.
Some teams are experimenting with drugs that are already prescribed to humans. Rapamycin, an immunosuppressant used in human transplant operations, has been shown to significantly extend the lives of mice, including very old ones. It seems to work by suppressing the mTOR complex, a set of genes that regulate metabolism. Meanwhile, a trial is looking at whether metformin, commonly prescribed for type 2 diabetes, might delay the development of other chronic diseases. Studies have found a correlation between metformin and delaying cancer, for example, but causation is not yet proven, nor has metformin been tested on healthy, non-diabetic older people.
Along with the mindset of treating one disease at a time, comes a licensing process for new drugs and therapies that approves them only for specific conditions. Statins are prescribed for heart disease, for example; insulin for diabetes. But even if we managed to eliminate one of the big killers — cancer, heart disease, stroke — that would bring us only a few extra years of life, because something else would get us instead. Plummeting rates of deaths from heart attack, while a great success, offer up more future victims to dementia, because ageing makes us vulnerable.
Part of the aim of the metformin trial is to persuade the US Food and Drug Administration to approve ageing as an “indication”, to signify that it can be “treated”. It is struggling to raise enough funding for clinical trials, because metformin is a generic drug, so offers insufficient profit to pharmaceutical companies.
The turning point may come through dogs, not humans. The wonderfully named Dog Aging Project, which has sequenced the genomes of more than 7,000 pets provided by keen owners, is conducting a clinical trial to see whether rapamycin can extend the longevity and health of our furry friends. Last year Loyal, a veterinary medicine company, announced that it had met the FDA’s “reasonable expectation of effectiveness” test for a drug it is developing to lengthen canine lives.
While these ideas progress through clinical trials, protocols and safety tests, there is one reliable, long-trialled way to reduce the risk of getting certain age-related diseases: exercise. Apart from the occasional injury, it has no serious side effects. Every scientist I have ever interviewed says that aerobic exercise and weight training are prerequisites for staying healthy, no matter what additional drugs we might take.
It may seem egotistical for the west to be seeking to extend lifespan, especially of pets, when tuberculosis and malaria are still rampant in large parts of the world. But if we could compress morbidity, it could also change the way we think. We fear old age long before we enter it. The possibility of a healthier, more active last few decades is a liberating thought in itself.