Dr Sebastian Grönke. Photograph: Max Planck Institute for Biology of Ageing
This is an extremely new field of research. “That’s why there’s so much interest,” says Sebastian Grönke at the Max-Planck Institute for Biology of Ageing in Cologne. Senolytics are particularly exciting, he says, because “they seem to still work very late in life” … “So it will be possible to study more quickly whether they actually work in humans, and they are applicable to people already at the end of their lives.”
Xu says that, in theory at least, it should prove impossible to build up a resistance to the drugs, “because senescent cells cannot proliferate”. Even more importantly, he says, there is significant data to show “that you don’t have to treat these patients every single day. You just treat them once a week or once a month … intermittent treatment is more than enough to have huge benefits.”
Senolytic drugs may also be able to play a part in other conditions. Xu has found that obesity can cause senescent cells to develop prematurely. “We also found that clearing senescent cells improves insulin sensitivity. So senolytic drugs not only work on ageing but also on obesity … Senescence is a connection between these two very common conditions.” While treating obese mice with senolytics, Xu observed that their anxiety levels reduced, too.
These aren’t the only potential added benefits. Grönke says that senescent cells “play a big role after cancer treatment”, developing as a result of chemotherapy and radiation therapy. “If senolytics can be used to help eliminate the damaged cells before they can spread, a detrimental side-effect of cancer treatment could be alleviated.”
Xu usually administers senolytics to mice at their equivalent of 70 to 80 years old in humans. “You don’t want to take it when you’re young, which would have zero effect, or harmful effects – but you don’t want to leave it too late. When to start giving the drug is a huge project and a huge question for us to answer over the next several decades.” He expects the ideal treatment age will differ from person to person, and that ultimately scientists will develop a blood or urine test that can assess the level of senescence present. “Some people age very fast, and some age very slow, so it could vary a lot,” he says.
So what can anyone determined to hold off the debilitating effects of age do while we await the wonder drugs? Intermittent fasting may have senescent effects. Grönke says caloric restriction, whereby “people eat less in general”, has been linked to healthy ageing and longevity. Mouse trials have shown that they can live 30 to 50% longer than control animals able to eat as much as they want. “It’s also well known that these animals have less senescent cells at comparable ages.” There is also a diet, developed by the gerontologist Valter Longo at the University of Southern California, that mimics the effects of fasting for those too frail to skip meals.
Of course, the risks of disease that increase with ageing are heightened by sedentary living, alcoholism and bad diet. Grönke recommends, along with a healthy diet, “reducing the amount of animal protein you consume – you can eat meat but ideally maybe once per week, maximum.” He says an association between low protein intake and longevity is well established in humans. “Ideally the protein should come from vegetables and not from meat.”
Just as obesity has been shown to increase the burden of senescent cells in tissue, exercise can reduce it, says Xu. But the effects were recorded in obese mice that had undergone a lot of vigorous exercise: “I don’t think the aged population is able to take intense exercise like that.”
So some signs are promising, and the potential is huge, but much still remains unknown about senolytics for ageing. There are clinical trials in the pipeline, with drugs for osteoarthritis leading the way, but an effective pill accessible to all is certainly not imminent. Xu puts it at five to 12 years away: “Theoretically I’m confident.” Those looking to live for ever might be wise to book that cryogenics appointment, just in case.