The primary reason for age-related immune decline lies in the thymus—a small organ near the heart where T-cells mature. The thymus begins to gradually shrink even in youth, and by age 75, it nearly entirely loses its functions. The body loses its capacity to generate new T-lymphocytes, and the remaining cells react to threats more slowly.
However, researchers from MIT and the Broad Institute devised a technique capable of rejuvenating the aging immune system. “As the immune system gets older, it starts to fade. We wanted to figure out how to sustain immune protection for as long as possible, and this led us to the idea of boosting immunity,” explains Mirko Fritsch, the study’s lead author.
Instead of trying to restore the thymus itself, the team of specialists decided to create a temporary substitute. They transformed the liver into a sort of factory for producing signaling molecules that the thymus usually releases to support T-cells. The choice of the liver was not random: it can synthesize large amounts of proteins even in old age, all circulating blood passes through it, and drug delivery to this organ is technically simpler than to many others.
The thymus gland in an adult person is gradually replaced by fatty tissue.
The scientists utilized mRNA in their work, which codes for three key T-cell maturation factors simultaneously: DLL1, FLT-3, and IL-7. The molecules were packaged into lipid nanoparticles and injected into the bloodstream of mice. Upon reaching the liver, the nanoparticles penetrated the liver cells—hepatocytes—which began to produce the necessary proteins.
“Our approach is more synthetic. We program the body to mimic the secretion of thymus factors,” says co-author Feng Zhang.
Experiments on 18-month-old mice—an age roughly equivalent to 50 years in humans—yielded impressive results. After a course of injections, T-cell populations significantly increased. During experimental vaccination, the number of cytotoxic T-lymphocytes targeting a specific antigen doubled compared to the control group. The effect was even more significant when combined with cancer immunotherapy: mice that received both mRNA therapy and a checkpoint inhibitor lived considerably longer.
The method developed by the scientists allowed for a substantial increase in the count of T-lymphocytes and an enhancement of their functionality.
It is important that all three factors were required for the full effect—none of them provided such results individually. Now, the researchers plan to conduct trials on other animals and possibly discover other signaling molecules.
“If we can restore the youth and full operation of the immune system, people will be able to remain healthy for longer,” Zhang emphasized.
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