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Anti-aging drugs key to improving COVID-19 vaccines among the elderly

October 29, 2020

Researchers are developing and testing drugs that could improve older people’s immune response to potential COVID-19 vaccines
For years, scientists have known that aging immune systems have a weaker response to vaccines
They now plan to rejuvenate these aging systems through the use of anti-aging drugs that will act on pathways linked to cell growth

In June, the US Food and Drug Administration announced that COVID-19 vaccines will only be considered viable and effective if they protect at least half of the people vaccinated. This declaration inevitably sparked off an international race towards a viable solution for the ongoing pandemic. Naturally, vaccines are designed to trigger the immune system to fight off foreign invaders. However, in older people, vaccines perform poorly due to immunosenescence. As the human body ages, the strength and effectiveness of its immune system weakens with time. And perhaps this explains why COVID-19 has ravaged older populations all over the world. Currently, there are about 50 COVID-19 vaccine candidates being tested in humans; but researchers are yet to determine whether or not they will be effective among the elderly. Take for example phase I of the Moderna vaccine trials carried out in Cambridge, Massachusetts. In a particular study of 40 individuals aged 56 and above, it was observed that the vaccine, mRNA-2273, produced similar antibody levels to those obtained across a younger group-set. Moreover, on September 9th, the Beijing-based Chinese biotech company, Sinovac, announced that its phase I/II study of 412 individuals aged between 60 to 89 years, produced similar antibody results to those of its younger subjects. However, phase I of the Pfizer and BioNTech study carried out in Mainz, Germany, determined that the vaccine, BNT162b2, triggered an immune response that was half as strong in older people as it was in young. Notably, the older test group that took the vaccine in this study produced more antibodies compared to people of the same age group who had contracted COVID-19. But in terms of protection against the virus, it was uncertain how these varying levels could play a part. Indeed, aging affects the human immune system in a number of complex ways. Older people tend to have fewer naive T cells, which are the first responders to foreign threats. They also have fewer B cells—which produce the necessary antibodies that latch on to invading pathogens—and consequently, destroy them. Although inflammation is a vital response characterized by a healthy immune system, older people tend to experience inflammaging; a unique kind of low-grade, chronic, inflammation. The chronic nature of this inflammation makes the immune system less responsive to new threats, as well as to vaccines. Fortunately, there is a promising class of anti-aging drugs aiming to change all this. These drugs work by inhibiting a protein known as mTOR. “mTOR is one of probably multiple biologic mechanisms that contribute to why we age and why our organ systems start to decline,” says Joan Mannick, co-founder and chief medical officer of resTORbio, a biotech company based in Boston, Massachusetts that’s geared towards developing anti-aging therapies. In fact, a number of anti-aging mTOR inhibitors, such as rapamycin, have already been approved; with at least four other groups conducting small trials on the drug as a potential COVID-19 therapy. One group has even conducted tests with rapamycin exclusively on individuals aged 60 and older! Another potential candidate is the type 2 diabetes drug, metformin; which has been observed to indirectly minimize mTOR’s activity in the body. A number of studies even suggest that people who take metformin are less likely to be hospitalized or die if they contract COVID-19. Carolyn Bramante, an obesity researcher at the University of Minnesota, details that diseases such as obesity and diabetes create the same kind of immune-deficiencies exhibited in old people. Together with his colleagues, he plans to launch a test trial on 1,500 people aged 30 and over to determine whether metformin could help prevent SARS-CoV-2 infection, or better yet, minimize the effects of those already infected. Moreover, Jenna Bartley from the University of Connecticut in Storrs, is evaluating whether metformin in small doses could boost the immune response to flu vaccines among the elderly. Her work is due to be published in a few weeks to come. If metformin does prove effective against COVID-19, researchers will have to figure out the exact reason why. “It’s about the dirtiest of dirty drugs out there. Metformin is a medication that you actually could give prophylactically for 12 months without having to do any follow-up, and it costs less than US$4 a month,” Bramante says. Another class of drugs, senolytics, could potentially be viable. These drugs work by eliminating the body of cells that have stopped dividing but won’t die. Usually, senescent cells are cleared out by the immune system; but as you grow older, they gradually accumulate and result in inflammation. In August, James Kirkland and a team at the Mayo Clinic launched a 70-person trial to determine whether fisetin—a senolytic naturally found in strawberries—could curb the progression of COVID-19 in individuals aged 60 and older. The trials would also determine whether fisetin could prevent COVID-19 infections in nursing-home residents. For now, however, no senolytics have been approved for clinical treatment. Indeed, in times of a pandemic, supporting an older immune system should be of utmost priority. Researchers believe that this renewed interest in understanding the defects of immune responses will not only have positive implications on defeating the coronavirus, but also on a host of viral infections, diseases, and perhaps even cancer.

References: https://www.nature.com/articles/d41586-020-02856-7

Anti-aging drugs key to improving COVID-19 vaccines among the elderly

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