MIT researchers have developed an experimental mRNA-based therapy that restored key immune functions lost with age in mice, improving vaccine responses and strengthening cancer immunotherapy, according to a study published in Nature.
As people age, the thymus — an organ that produces and trains T cells — shrinks, reducing the supply of new immune cells and weakening defenses against infections, vaccines, and cancer. Past efforts to slow this process focused on repairing the thymus itself, but most showed limited benefits or serious drawbacks.
The new approach takes a different route by turning the liver into a temporary source of immune-supporting signals that normally fade with age.
Researchers delivered messenger RNAs encoding three key factors — DLL1, IL-7, and FLT3-L — into liver cells using lipid nanoparticles. The liver then produced these signals for a short time, helping restore immune balance.
In aged mice, the treatment increased the number of naïve T cells, partially revived thymus function, and improved immune cell diversity without signs of toxicity or autoimmunity. Vaccine responses doubled in some models, and older mice showed stronger responses to cancer immunotherapy. In an aggressive melanoma model, 40% of treated aged mice completely rejected tumors, while untreated mice did not survive.
Safety tests in several sensitive disease models showed no worsening of autoimmune conditions, and the immune effects faded after treatment stopped, suggesting the therapy is reversible.
The findings suggest that short-term, liver-targeted mRNA treatments could one day be used to temporarily strengthen immune defenses in older adults, such as before vaccination or cancer therapy. While the research is limited to mice, scientists say it opens a new path for addressing age-related immune decline.
