Imagine there was a pill that could slow the ageing process — a medicine that could delay the fragility, osteoarthritis, memory loss, macular degeneration and cancers that cause problems in old age.
With the science of senolytics, it could happen. Senolytics is a developing — and highly anticipated — area of anti-ageing medicine. Many of the world’s top gerontologists have already shown the possibilities in animals and are now beginning human clinical trials, with promising results. If the studies continue to be as successful as hoped, those who are currently middle-aged could become the first generation of old people who stay youthful longer — with a little medical help.
The economics of ageing
Most scientists studying how long people live are more interested in increasing what they call a person’s “healthspan” than they are in increasing a person’s lifespan. That is to say, they want to help people age with less pain and illness, with a better quality of life. This would be good not only for old people but also for economies.
In England and Wales, life expectancy has risen by almost 25 years in the past century. The Office for National Statistics (ONS) predicts that the UK’s population of over-65-year-olds will grow by 8.6 million (about the population of London) over the coming 50 years. This will be expensive: the National Health Service (NHS) spends more than twice as much on 65-year-olds as it does on 30-year-olds — 85-year-olds cost more than six times as much.
“Healthy ageing is a huge project — it can come with a lot of benefits, both for governments and older patients themselves,” says Ming Xu, an assistant professor at the University of Connecticut’s Center on Aging. As Xu notes, ageing is the biggest risk factor for most chronic diseases. The goal of his lab is to find new ways to slow down the ageing process and to prevent disease at the same time.
Xu works in senolytics, a branch of medicine that targets senescent cells, the different kinds of faulty cells that have been identified as contributing to ageing. These so-called zombie cells multiply as we age, giving off substances that cause inflammation and turn other healthy cells senescent, leading to tissue damage throughout the body.
Of mice and men
Xu was part of a team at the Mayo Clinic, an academic medical centre in Minnesota, which showed in 2011 that “using a genetic trick to remove these senescent cells can significantly improve health and lifespan” in prematurely aged mice. In 2016, the same group achieved similar results in naturally aged mice. The team made public a striking picture of two elderly mice born at the same time, from the same mother. In the picture, the mouse cleared of its senolytic cells looks agile and has shiny fur, while the other mouse looks shrunken and greying.
The picture helped bring in millions from investors, including Amazon founder Jeff Bezos and PayPal co-founder Peter Thiel, who saw the promise of replicating the same results in humans. According to Kevin Perrott, president of the Washington, DC-based Global Healthspan Policy Institute, the response showed that Silicon Valley tended to view ageing as a problem that could be solved “with enough time and enough steps”. In 2018, he said: “The size of the return is huge. If you’re able to bring anything like that to the market, you have something that’s universally needed.”
The “genetic trick” used to destroy senescent cells in the mouse studies was, however, not viable as a safe treatment for people. Unity Biotechnology is one company that raises funds to develop medicine that could safely clear zombie cells from the human body.
Treating a non-disease
The first problem for the people at Unity and the other scientists working in senolytics is to identify what, exactly, they are trying to treat. In order for a drug to be approved, it has to be shown to be effective in treating a disease. But ageing is a natural process, and, far from a localized problem, it involves a breakdown of the whole system.
The first trials in senolytics are targeting specific conditions such as age-related macular degeneration, glaucoma and chronic obstructive pulmonary disease (which includes emphysema). Most trials are in the early stages, working on rodents or human tissue in petri dishes. In 2019, however, a small human trial showed an improvement in the distance patients were able to walk after treatment.
In the same year, a pre-clinical pilot trial for injecting a senolytic drug into the knees of people with osteoarthritis showed mixed, but promising, results. In the first part of the study, in which patients got varying doses of the drug, significant reduction in pain and improvements in function were observed. In the second part of the experiment, however, in which patients received the maximum dose, the scientists didn’t see significant benefits.
Into the unknown
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 patients do not need daily treatment to profit from it. “Intermittent treatment is more than enough to have huge benefits.”
Senolytic drugs may help with other problems. “We also found that clearing senescent cells improves insulin sensitivity. So senolytic drugs not only work on ageing but also on obesity,” says Xu. While treating obese mice with senolytics, he observed that their anxiety levels were reduced, too.
These aren’t the only potential benefits. Grönke says that senescent cells develop 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.”
“When to start giving the drug is a huge project and a huge question for us to answer over the next several decades,” says Xu. “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.” He expects the ideal treatment age will differ from person to person, and that scientists will develop a blood or urine test that can assess a person’s level of senescence. “Some people age very fast, and some age very slow, so it could vary a lot,” he says.
In the meantime
So, what can you do to delay the effects of age while waiting for the wonder drugs? Grönke says that eating less has been linked to healthy ageing and longevity. Trials have shown that mice can live 30 to 50 per cent 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.”
Of course, the risks that increase with ageing are made worse by sedentary living, alcoholism and a bad diet. Grönke recommends “reducing the amount of animal protein you consume — you can eat meat but, ideally, maybe once per week, maximum.” He says it’s well known that humans who eat little protein live longer. “The protein should come from vegetables and not from meat.”
Some signs are promising, and the potential is huge, but much still remains unknown about senolytics as a treatment for ageing. There are clinical trials planned, but an effective pill accessible to all will not be available soon. Those looking to live forever might be wise to book that cryogenics appointment, just in case.
© Guardian News & Media 2019