Infectious disease is a far greater risk for the old than for the young. But then so is cancer. Both are conditions driven by the age-related failure of immune system competence, a growing inability to respond to vaccines and to destroy pathogens and errant cells, a state known as immunosenescence. Further, the failing immune system becomes inappropriately overactive at the same time as losing its efficacy, generating chronic inflammation that disrupts normal tissue function and spurs the development of numerous age-related diseases. Restoring a youthful immune function would be enormously beneficial and greatly reduce mortality and age-related disease across the board in older people. While this is a topic of interest in the research community, nowhere near enough resources are directed to achieving this goal, given the enormous cost and suffering that results from immune aging.
Unlike fine wine, the human body does not improve with age. Hearing fades, skin sags, joints give out. Even the body's immune system loses some of its vigour. This phenomenon, known as immunosenescence, might explain why older age groups are so hard-hit by COVID-19. And there is another troubling implication: vaccines, which incite the immune system to fight off invaders, often perform poorly in older people. The best strategy for quelling the pandemic might fail in exactly the group that needs it most.
The human immune system is mind-bendingly complex, and ageing affects nearly every component. Some types of immune cell become depleted: for example, older adults have fewer naive T cells that respond to new invaders, and fewer B cells, which produce antibodies that latch on to invading pathogens and target them for destruction. Older people also tend to experience chronic, low-grade inflammation, a phenomenon known as inflammageing. Although some inflammation is a key part of a healthy immune response, this constant buzz of internal activation makes the immune system less responsive to external insults. The upshot is a poorer reaction to infections and a dulled response to vaccines, which work by priming the immune system to fight off a pathogen without actually causing disease.
Many of the immune changes that come with ageing lead to the same result: inflammation. So researchers are looking at drugs that will calm this symptom. A class of drug, called senolytics, helps to purge the body of cells that have stopped dividing but won't die. These senescent cells are typically cleared by the immune system, but as the body ages, they begin to accumulate, ramping up inflammation. In August, a team launched a 70-person trial to test whether a senolytic called fisetin can curb progression of COVID-19 in adults aged 60 or older. They also plan to test whether fisetin can prevent COVID-19 infection in nursing-home residents.
In general, developing medications to improve immune function seems like a much smarter strategy than creating vaccines specifically for elderly people. Individual vaccines target specific pathogens, but an immune-boosting medication could be used with any vaccine. "I think the net result of all this will be renewed interest in understanding the defect in the immune response in the elderly. COVID-19 has brought to the front something that a lot of people have ignored."