Explore a breakthrough in healthy ageing. MIT scientists use mRNA to make the liver boost the immune system, rejuvenating T cells for better vaccine and cancer defense.
MIT scientists have discovered a method to boost the immune system in older animals. As individuals age, their immune system weakens, which is partly because T cells, a type of white blood cell that helps fight infections and cancer, become less effective. The body produces fewer T cells with age, and the ones that remain often respond more slowly to threats. This weakens the immune system and makes older people more vulnerable to illnesses and less responsive to vaccines. The study was published in the journal Nature.
Researchers at MIT and the Broad Institute have found a way to temporarily improve the immune system in older mice. Their method helps the body produce more and more diverse T cells even when the immune system is not working as well. Although this research is still in the early stages, it could one day help people stay healthier as they grow older.
Why the Immune System Weakens with Age
The immune system relies on T cells, which are made in the thymus, a small organ located in front of the heart. In the thymus, immature cells learn to recognize harmful germs while not attacking healthy body tissues. The thymus also sends signals that help T cells develop and survive. However, the thymus starts shrinking early in life, often beginning in adulthood. This process, called "thymic involution," leads to fewer new T cells being produced over time. By around the age of 75, the thymus is usually no longer active.
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Scientists have long looked for ways to support the immune system as people age. Some previous attempts involved giving growth factors through the bloodstream, but these can have serious side effects. Other methods, such as regrowing thymus tissue using stem cells, are still experimental.
Turning the Liver into a Temporary Helper
Instead of focusing on the thymus directly, the MIT team explored whether another organ could be used to support T cell production. They focused on the liver, which is effective at making proteins even in old age and is easy to deliver genetic instructions to. Moreover, all the blood in the body passes through the liver, allowing immune cells to be exposed to signals released there.
The researchers used messenger RNA (mRNA), the same technology used in some COVID-19 vaccines. mRNA carries instructions for making specific proteins. The team packaged mRNA into tiny fat droplets and injected them into the bloodstream. These droplets collected in the liver, where liver cells absorbed the mRNA and started producing important immune signals.
Stronger Immune Responses in Older Mice
These signals helped immature immune cells develop into fully functional T cells. When the scientists tested this method in older mice, the results were impressive. Mice aged similarly to humans in their 50s received repeated doses over four weeks because the mRNA only lasts briefly in the body. After treatment, the mice had more T cells, and these cells functioned better than before.
The team then tested how well the mice responded to a vaccine. Older mice that received the mRNA treatment produced twice as many T cells against the vaccine compared to untreated mice of the same age.
The treatment also enhanced responses to cancer immunotherapy. When mice were given both the mRNA treatment and a common drug used in cancer treatment that removes "brakes" from the immune system, they lived longer and fared better than mice given the drug alone.
Importantly, the researchers found that all three immune signals were necessary to see these benefits. Using just one or two was not enough.
Looking Ahead
The scientists note that this work is still experimental and has only been tested in animals. Next, they plan to study this approach in other models and explore whether additional signals could further strengthen the immune system. They also want to understand how this treatment affects other immune cells, such as B cells, which produce antibodies.
While human treatments are still far off, this research offers a promising new way to think about healthy ageing, not by stopping time, but by helping the body defend itself better as the years go by.
