As we get older, our immune system slowly loses its edge.
One of the biggest changes happens in T cells, a type of white blood cell that helps the body fight infections and cancer.
With age, T cells become fewer in number and slower to respond, leaving older adults more vulnerable to illness and reducing the effectiveness of vaccines and cancer treatments.
Now, researchers have discovered a promising new way to temporarily restore some of this lost immune strength.
In a new study, scientists showed that it is possible to “rejuvenate” the immune system in aging mice by briefly reprogramming cells in the liver to support T cell growth and survival.
The problem starts with the thymus, a small organ located near the heart. The thymus acts as a training ground for T cells, helping them mature and develop the diversity needed to recognize many different threats.
Unfortunately, the thymus begins shrinking surprisingly early in adulthood. By the time people reach old age, it has lost much of its function, and the supply of new T cells drops sharply.
Rather than trying to repair or replace the thymus itself, the research team took a different approach.
They asked whether the body could be engineered to temporarily take over some of the thymus’s job. Their solution was to turn the liver into a short-term “factory” that produces signals normally released by the thymus.
The liver was an ideal target for several reasons.
It remains highly active even in old age, it is very good at making proteins, and it is relatively easy to deliver genetic instructions to liver cells. Importantly, all circulating blood passes through the liver, meaning immune cells can readily receive the signals produced there.
The researchers used messenger RNA, or mRNA, to deliver instructions for making three key immune-supporting molecules. These molecules help immature T cells survive, mature, and expand.
The mRNA was packaged into tiny lipid particles and injected into the bloodstream. Once the particles reached the liver, liver cells began producing the immune-boosting factors for a short time.
Because mRNA naturally breaks down quickly, the treatment did not permanently change the cells. Instead, the mice received several injections over a few weeks to maintain the effect.
The results were striking. Older mice that received the treatment developed larger and more diverse T cell populations. Their immune systems looked and behaved more like those of younger animals.
When these mice were given a vaccine, their T cell response was much stronger than that of untreated mice of the same age. The treatment also improved the effectiveness of cancer immunotherapy. Older mice receiving both the mRNA treatment and an immune checkpoint drug survived longer and responded better to treatment than mice that received the cancer drug alone.
The researchers found that all three immune factors were necessary to achieve these benefits. Using only one or two was not enough to fully restore immune function.
While this work is still at an early stage and has only been tested in mice, it opens the door to a new way of thinking about immune aging. Instead of trying to permanently rebuild damaged organs, short-term and repeatable treatments might help older people maintain stronger immune defenses and stay healthier for longer.
