mice study points to new way to rejuvenate aging immune systems

Researchers at mit and the broad institute used temporary genetic programming in liver cells to restore more youthful t cell responses in aged mice, boosting vaccine and cancer immunotherapy effectiveness. The strategy mimics key thymus signals using mrna-loaded lipid nanoparticles that turn hepatocytes into short-lived protein factories.

Immune function typically weakens with age as the thymus shrinks, reducing the organ’s ability to mature and diversify t cells. As a result, populations of these immune cells become smaller and less capable of reacting quickly to pathogens, leaving older individuals more vulnerable to infections and disease. To counter this decline, a research team at mit and the broad institute has developed an approach that temporarily programs cells in the liver to enhance t cell performance.

The researchers set out to create a functional stand in for the thymus by turning hepatocytes into a “factory” for t cell stimulating signals. They identified three key factors that usually promote t cell maturation and encoded them into mrna sequences that could be delivered using lipid nanoparticles. When injected into the bloodstream, these nanoparticles accumulate in the liver, where hepatocytes take up the mrna and start manufacturing the proteins encoded by the sequences, effectively supplying the signals that aging thymus tissue no longer provides in sufficient quantities.

In studies with aged mice, the treatment led to much larger and more diverse t cell populations following vaccination, indicating a restored capacity to recognize and respond to new antigens. The treated mice also showed improved responses to cancer immunotherapy, suggesting broader benefits for disease control in older immune systems. The senior researcher on the project, professor feng zhang, expressed hope that if this type of temporary mrna based treatment can be adapted safely for humans, it could help people remain free of disease for a longer span of their lives by revitalizing t cell function without permanently altering organs.

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