Senolytics
Laut wissenschaftlicher Studien ließe sich durch eine einfache Behandlung der Alterungsprozess schon in wenigen Jahren verlangsamen. AMY FLEMING berichtet, wie das funktionieren soll.
Slowing the ageing process
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
Those who are currently middle-aged could become the first to stay youthful
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 agerelated 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.
The first problem for scientists in senolytics is to identify what exactly they are trying to treat
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.
Mehrere kurze Auszeiten können so wohltuend sein wie ein langer Urlaub. Manche Firmen bieten gar eine unbegrenzte Zahl freier Tage. Warum aber schöpfen viele Arbeitnehmer die ihnen zustehenden Urlaubstage nicht voll aus? Und Führungskräfte gehen auch nicht gerade mit gutem Beispiel voran. JULIAN EARWAKER berichtet.
The American poet Henry Wadsworth Longfellow (1807–82) was once quoted as saying that people didn’t achieve great things all of a sudden. They did so by “toiling” while others “slept”. This kind of thinking is what puts people off taking leave from work. But everyone needs a break — even Longfellow.
Research by healthcare firm BUPA shows that workers who take vacations, whether long or short, enjoy better mental and physical health than those who do not. The Framingham Heart Study, for example, found that women who don’t take holidays are 50 per cent more likely to have a heart attack than those who take a break. For men, it’s 30 per cent. Holidays help people “interrupt the cycle of stress”, says Elizabeth Scott, a wellness coach at Verywellmind.com. They can also “lead to sharper thinking and increased creativity”.
Research also shows that taking a break can improve productivity and performance upon return to work. Realbusiness. co.uk reports that after taking holidays, twothirds of people feel greater job satisfaction and more productive at work. Meg Selig, a counselling expert writing in Psychology Today, says that breaks “increase productivity and creativity … [and] restore motivation, especially for longterm goals.”
To take advantage of the benefits of breaks, some companies have offered their staff unlimited annual leave — allowing their staff to take as much holiday as they like. This is not a new idea. When Sir Richard Branson introduced the perk for staff at Virgin five years ago, it was part
of a movement towards flexible working introduced by IBM in the 1990s and has been followed by Netflix, Glassdoor, Linkedin and others.
Some businesses have had success with the policy. Since adopting unlimited paid leave, Inventium, an innovation consulting firm in Melbourne, Australia, has seen sick leave halve and retention increase. To many employees, the concept of unlimited leave sounds as idyllic as the Virgin website picture of Sir Richard lying under a palm tree looking out at a blue sea.
Such policies have some hidden benefits for the company as well as its staff. Pilita Clark, business columnist at the Financial Times, says that employers use unlimited leave as a way of saving millions in unused leave liabilities when employees move on to new jobs. Companies “can safely offer bottomless holidays knowing most employees will never take them, especially in the US,” she adds.
Across the globe, millions of workers are failing to take their full holiday entitlement. The Brits wasted 163 million annual leave days in 2016. More than 30 per cent of UK workers are guilty of not using their full holiday entitlement. Figures from Glassdoor.co.uk show that in the UK, only 35 per cent of 18 to 24yearolds are using all their annual leave allowance. In the US, workers take only an average of 16.7 days’ holiday each year.
What’s the best way to get reluctant vacationers to take muchneeded holidays? The attitude of senior staff and management is key. Not only should managers encourage staff to take leave, but they should also ensure that timecritical tasks are given to someone else and remind their teams that annual leave is not an optional extra.
Some workers think it is too much trouble to organize their leave. To make it easier, Totaljobs.com says that employees should give their employers plenty of notice of a planned holiday, book travel and hotels in advance, delegate important work to colleagues and, most importantly, leave their work smartphone and other technology at home. “Time off,” says BUPA, “should mean time off.”
So, what if you’re a workaholic businessperson who would rather not take a holiday? Telegraph.co.uk says it’s time to let go of your ego and recharge by spending time with family and friends. You should think of leave as an investment — and don’t cheat!
There’s another picture of a smiling Sir Richard, sitting on a terrace with a deep blue sky beyond. So, what happens if you take a holiday and can’t stand the thought of getting back to work? “You probably do not need another vacation,” says travel expert Brian de Haaff on Huffpost.com. “You need a new job.”
Across the globe, millions of workers are failing to take their full holiday entitlement