Anti-aging drugs are being tested as a way to treat covid

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Covid-19 is far more likely to kill you if you’re old. One reason is that older immune systems are less able to deal with infections and recover from them. Why not look into drugs that can make our bodies younger again? Clinical trials are underway around the globe to test drugs that reverse the effects of ageing, boost the immune system, and rejuvenate old, damaged cells.

Some scientists avoid the term “anti-aging” due to its connotations of snake oil. However, these drugs target the biology behind aging. It is intuitive to use them to aid older bodies in fighting off any infection. These drugs can be used to help anyone suffering from a weak immune system, whether it is due to age, chronic illness, or childhood disease.

We certainly need a new way of treating the disease. Covid-19 might never go away. Even in countries with high immunity, it can still kill and hospitalize people. But only a handful of effective treatments have been found, including antiviral, antibody, and steroid drugs–and these might not work as well against future variants.

And age not only raises someone’s chances of getting seriously ill with covid-19 but also increases the risk of developing long covid. These drugs could be used to treat covid if they work.

Younger defenses

Age withers the immune system in many ways. Older people are more susceptible to getting the flu and their immune systems don’t respond as strongly to vaccines. Some immune cells may become less capable of killing harmful bacteria or viruses, making them more vulnerable. Some immune cells are more susceptible to infection and can produce more damaging inflammation, which can cause tissue damage.

This degradation of the immune system may also occur in younger people who have biologically older bodies. These systems function more like older people than those of their age. Conditions that make a person more vulnerable to the coronavirus, such as diabetes and lung and heart diseases, seem to be linked to having an older biological age. And people who had a higher-than-expected biological age 10 years before the start of the pandemic were more likely to die if infected.

Janet Lord is a researcher at the University of Birmingham, UK. He studies the effects of ageing on the immune system. His research has focused on neutrophils, a type of immune cell that can go haywire in older people. These cells are found in the blood and make a beeline to the area of infection. Lord says that older people can experience significant damage from the cells as they tend to wander off in the wrong direction. They can burrow through tissue “like aworm burrowing through soil.” She says that older people are more likely to get an infection.

Her team has been trying to find a way for neutrophils to be more effective in fighting infections. The team has found that blocking the activity of an enzyme that influences how the immune system works seems to return neutrophils to a younger state in the lab. Lord discovered that statins, which are drugs commonly prescribed to lower cholesterol, may have a similar effect.

“Imagine if, in the pandemic, everyone had the immune system of a 20-year-old”

Kristen Fortney, cofounder and CEO of BioAge Labs

A few years ago, Lord and her colleagues ran a small clinical trial of a statin in people aged 68 to 90 who were hospitalized with pneumonia. Simvastatin was administered to approximately half of the volunteers seven days a week, once daily. Blood tests showed that the neutrophils from people who took statins behaved more like younger cells and were better at tackling infection. And while 20% of those who took a placebo died within 30 days of the trial, only 6% of those who took the statin did. The approach, if it is successful, may also be helpful in helping older immune system cope with coronavirus infection. Lord points to evidence from China that suggests there’s a link between statin use and survival against covid-19. Xiao-Jing Zhang at Wuhan University and colleagues compared the outcomes of 13,981 people who were admitted to hospital with covid-19 in Hubei province, 1,219 of whom were taking statins. The team found that the people who took statins were less likely to die and more likely to recover well.

“A lot of us believe that the health benefits of statins are probably more related to them correcting the immune system than to lowering cholesterol,” says Lord. There is hope that statins may also be beneficial for people suffering from long-term covid. A clinical trial is underway across the UK to find out whether a daily statin might help people recover from covid-19 and prevent lasting symptoms.

A company called BioAge Labs is also hunting for anti-aging treatments that might treat covid-19 by slowing or even reversing the decline of the immune system. “Imagine if, in the pandemic, everyone had the immune system of a 20-year-old,” says Kristen Fortney, the cofounder and CEO. “It would have been very different.”

The company’s approach is to learn from people who age successfully–living long lives in good health. It has been working with biobanks to discover clues in the genes, cells and metabolism of long-lived people who might be able to reveal new anti-aging drug targets.

BioAge Labs’ experimental drug for covid-19 blocks a receptor on dendritic cells, branching cells that help control how the immune system responds to an infection but seem to cause too much inflammation later in life. It has shown great promise in mice and appears to rejuvenate both neutrophils and dendritic cells.

In a study published in March, mice were given a lethal dose of the virus that causes covid-19. Fewer than 10% of the treated mice died, but all the others did. The drug is currently being trialed in older people hospitalized with covid-19 in the US, Brazil, and Argentina, and Fortney says she hopes to have a better idea of whether it works in people by the end of the year.

Immune retune

Another approach to rejuvenating the immune system may also have the added benefit of helping to treat covid. The target enzyme is mTOR, which regulates metabolism. Drugs that block this enzyme–such as rapamycin–allow mice and other animals to live longer. Joan Mannick, cofounder of Tornado Therapeutics, says that Rapamycin increases life span in all species it has been tested.

Back in 2014, when Mannick was at the pharmaceutical company Novartis, she and her colleagues showed that a drug similar to rapamycin could improve the way older people’s immune systems respond to the flu vaccine. She says, “It’s like tuning a car.” “You have to sort of retune your mTOR to a young level to allow cellular function to come back to normal.”

Since then, other trials have found that the drug helps prevent respiratory tract infections in older people, although a further trial failed to show any effect. This could be because the study focused on symptoms rather than lab-confirmed infections.

Mannick has been exploring the effects of rapamycin-like drugs in covid-19. Her trial was conducted in nursing homes that are experiencing an outbreak of the disease. Half of the participants received the drug and half received a placebo for four weeks. Among those given a placebo, “25% of them developed severe covid, and half of them died,” says Mannick, who has yet to publish the work. None of those taking the drug developed any covid-19 symptoms. There are many strategies to help the aging immune system fight against covid better,” she said. “Aging is the biggest risk factor for severe covid, and it’s a modifiable risk factor.”

Fortney hopes to extend the use of her drug beyond covid-19; a rejuvenated immune system could theoretically fend off many other viral and bacterial infections. Stanley Perlman, a University of Iowa coronavirologist, was part of the research that BioAge did on the covid drug in mice. He has plans for future pandemics. “Next time there’s another coronavirus in 2030, maybe all this information will be very useful then,” he says.

Out with the old

The immune system is not the only target of antiaging drugs. Others aim to clear out aged cells. Most cells in our bodies divide at a certain point. They should be disposed of once they have reached this point. Some cells can linger, but this is not always the case. These cells stop dividing and instead produce toxic chemicals that cause inflammation in the surrounding areas and beyond.

Cells that do this are known as “senescent” and accumulate in our organs with age. They have been linked to a growing number of age-related diseases such as diabetes, heart disease and cataracts. They may also play a significant role in coronavirus infection.

James Kirkland, a researcher at the Mayo Clinic in Rochester (Minnesota) who studies aging, cell senescence, and coronavirus, has found evidence that coronavirus infects senescent more quickly than non-senescent. He also believes that senescent cells release chemicals which make non-senescent neighboring cells infected with the virus.

Not only do these cells take on more coronavirus, but they also appear to provide a breeding ground for new virus variants. Kirkland says that there is evidence that coronavirus-infected senescent cells can cause virus mutations. “So they may even be a cause of viral mutations.”

As an added concern, the coronavirus can make healthy cells senescent. Given all this, senescence has become an obvious target of both anti-aging and covid-19 therapies. Studies in mice and hamsters suggest that compounds that kill senescent cells can improve the symptoms of covid-19 and boost the chances of survival.

Now, Kirkland and his colleagues are finding out if drugs that kill senescent cells–known as senolytics–can help people with covid-19. His team is trialing the drugs in people with covid-19 in three settings: at home, in hospitals, and in nursing homes. The drug Kirkland is using is essentially a plant extract. It is taken from a gum tree that is native to China. Fisetin is also found in cucumbers and strawberries. He believes this means that it is safe, but he emphasizes that he doesn’t know for sure. He says, “I strongly advise people to not take these drugs outside of the context of carefully controlled clinical studies.” “We don’t know the downsides of them.”

Although senolytic drugs don’t specifically target the immune system, researchers believe they restore immune cells to a more youthful state. Researchers have realized that there are many mechanisms that contribute to aging. However, targeting one mechanism can bring benefits to others. This has been evident over the past decade.

“I believe the future will be combining different genetic interventions with disease-specific interventions,” Kirkland says. “These kinds of interventions could combine with existing interventions to increase the chance of recovering.”

That recovery could be from any number of infections or age-related diseases, but covid-19 is an important first target, scientists say. Cases have more than doubled in the US in the last month as the omicron variant has surged, and as of May 13, weekly figures are up 29% on the previous week. Over 18,000 people in the US are currently hospitalized with covid-19, and that figure is rising. It’s amazing how fast [the virus], mutates,” Kirkland says. “It’s going be very difficult to use traditional vaccines and antiviral methods to keep up with [new variants].,” Kirkland said. I’m worried about that.”

Perlman agrees that we need a new, age-based approach to tackling covid-19. He says that there could be a more severe variant. “I think it would be foolish to think that we’re finished.”

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