MIT scientists find a way to rejuvenate the immune system as we age
As the immune system weakens with age, scientists have found a way to restore some of its lost strength. By delivering mRNA to the liver, they created a temporary source of immune-boosting signals that normally come from the thymus. Older mice treated this way produced more effective T cells and responded far better to vaccines and cancer treatments. The strategy could one day help extend healthy years of life.
As people get older, the immune system often becomes less effective. Populations of T cells shrink, and the remaining cells may respond more slowly to germs. That slowdown can leave older adults more vulnerable to many kinds of infections.
To address this age related decline, scientists from MIT and the Broad Institute developed a method to temporarily reprogram liver cells in a way that strengthens T cell performance. The goal is to make up for the reduced output of the thymus, the organ where T cells normally mature.
In the study, the team used mRNA to deliver three important factors that support T cell survival. With this approach, they were able to rejuvenate the immune systems of mice. Older mice that received the treatment produced larger and more varied T cell populations after vaccination, and they also showed improved responses to cancer immunotherapy.
The researchers say that if this strategy can be adapted for patients, it could help people stay healthier as they age.
"If we can restore something essential like the immune system, hopefully we can help people stay free of disease for a longer span of their life," says Feng Zhang, the James and Patricia Poitras Professor of Neuroscience at MIT, who has joint appointments in the departments of Brain and Cognitive Sciences and Biological Engineering.
Zhang is also an investigator at the McGovern Institute for Brain Research at MIT, a core institute member at the Broad Institute of MIT and Harvard, and an investigator in the Howard Hughes Medical Institute. He is the senior author of the new study. Former MIT postdoc Mirco Friedrich is the lead author of the paper, which was published in Nature.
The Thymus and Why T Cells Decline With Age
The thymus is a small organ located in front of the heart, and it is essential for building a healthy supply of T cells. Inside the thymus, immature T cells go through a checkpoint process that helps create a diverse set of T cells. The thymus also releases cytokines and growth factors that help T cells survive.
But beginning in early adulthood, the thymus starts to shrink. This process is called thymic involution, and it reduces the body's ability to produce new T cells. By about age 75, the thymus is essentially nonfunctional.
"As we get older, the immune system begins to decline. We wanted to think about how can we maintain this kind of immune protection for a longer period of time, and that's what led us to think about what we can do to boost immunity," Friedrich says.
Earlier efforts to rejuvenate the immune system have often focused on sending T cell growth factors through the bloodstream, but that approach can cause harmful side effects. Other researchers are investigating whether transplanted stem cells could help regrow functional thymus tissue.
A Temporary Liver Factory Powered by mRNA