Just as skin wrinkles and the back begins to stoop, the cells inside our bodies also age. In particular, when immune T cells age, immune function declines, making people more vulnerable to infectious diseases and cancer. As a result, older adults face increased risks of various illnesses and complications. Recently, a technology that temporarily rejuvenates aged immune cells using the liver has been developed, drawing attention.
A joint research team from the Massachusetts Institute of Technology (MIT) and the Broad Institute announced that they successfully restored an aged immune system by reprogramming liver cells with mRNA technology. The study was recently published in the international journal 《Nature》.
T cells mature in the thymus, located in front of the heart, but the thymus begins to shrink starting in the 20s and has almost completely lost its function by the 70s. When this phenomenon, known as “thymic involution,” cuts off the supply of new T cells, immune function drops sharply. Until now, researchers have tried approaches such as directly injecting T-cell growth factors or transplanting stem cells, but these efforts ran into problems such as severe toxicity or low efficiency.
Instead of repairing the thymus directly, the MIT team focused on the liver, which has an exceptional capacity to produce proteins. The researchers loaded lipid nanoparticles (LNPs) with mRNA blueprints for three proteins essential for T-cell maturation and survival (DLL1, FLT3L, and interleukin-7) and injected them into the blood of aged mice. Once these particles reached liver cells, the liver immediately began producing immune-boosting proteins according to the blueprints.
The effects appeared right away. When this treatment was administered to 18-month-old aged mice—roughly equivalent to humans in their 50s—the number and diversity of T cells increased noticeably. In vaccine-response experiments, treated mice produced twice as many antigen-responsive T cells as untreated mice.
Especially dramatic results were seen in experiments involving older mice with aggressive skin cancer (melanoma). All mice that received only existing immunotherapy died within 21 days, but in the group that also received the mRNA treatment, “complete remission,” in which tumors disappeared entirely, was confirmed in as many as 40% of the mice. The findings suggest that T cells weakened by aging regained their function, reactivating the anti-cancer response.
Above all, this approach is considered highly safe because, given the nature of mRNA-based technology, the effect fades quickly once dosing is stopped.
This study is significant in that it is the first to demonstrate the possibility of rebooting the entire immune system through the liver even when thymus function has stopped. The team plans to conduct additional validation in other animal models and expand the research to examine effects on other immune cells, such as B cells.
If these findings lead to practical applications, they are expected to help reduce a range of diseases driven by age-related immune decline in older adults and contribute to extending healthspan.
