The immune system ages silently. It does not warn with a specific symptom, but rather The wear and tear becomes visible when an infection takes longer to clear, a vaccination is less protective, or the cancer faces fewer obstacles..
for years, The great desire of the science of longevity was to stop this decline and restore the mobility of the defenses of youth.. Now a team from MIT and the Broad Institute is proposing the idea of not directly rejuvenating the immune system, but Teach the body to temporarily create a younger version of itself.
The study, published in Nature, focuses on the thymus, a small organ in front of the heart that acts as a school for T lymphocytes, the key cells to detect and eliminate threats. In this environment Lymphocytes are trained and selected to form a diverse and effective defense. The problem is that the thymus gland shuts down very early: from early adulthood it progressively shrinks and by the age of 75 it is virtually inactive..
“As you get older, your immune system begins to deteriorate.”explains Mirco Friedrich, main author of the work. The question, he says, is not how to completely reverse this process, but rather how to extend protection longer.
The team’s reaction was unconventional. Instead of trying to reactivate the aging thymus or flooding the blood with immunological factors – a strategy with risks and side effects – they opted for a biologically engineered solution. “Our approach is rather synthetic,” says Feng Zhang, co-author of the study.
The idea: Design the body so that it imitates the signals of a young thymus gland for a while. The organ that was supposed to take on this role was the liver. This organ is capable of producing large amounts of proteins even in advanced age and is easily accessible to messenger RNA-based therapies. It became a temporary factory for immunological signals.
To achieve this, the researchers developed lipid nanoparticles loaded with mRNA encoding three essential factors for T lymphocyte survival and maturation: DLL1, FLT-3 and IL-7. After injection, these particles accumulate in the liver, where the cells begin to produce signals similar to those in the thymus.
The results in old mice – comparable to people in their 50s – were astonishing.. After several weeks of treatment, both the number and diversity of the T cell populations increased. Not only did the immune system appear younger, but also more flexible and able to respond to a wider variety of threats. This improvement was reflected in the response to the vaccines: treated mice doubled the number of specific cytotoxic T lymphocytes after receiving an experimental vaccine compared to animals of the same age that had not been treated.
The effect was even clearer in the fight against cancer. Combined with immunotherapy, which releases the brakes on the immune system, the strategy allowed the treated mice to live longer and show higher survival rates than those that received the antitumor drug alone. None of the three factors worked alone; Only by acting together could they temporarily recreate an environment that was functionally similar to that of a young thymus.
The study doesn’t promise eternal youth or absolute immunity, but it does suggest that some of the decline in the immune system may not be irreversible.. “If we can restore something as essential as the immune system,” Zhang concludes, “we may be able to help people stay disease-free for a longer part of their lives.”. Crucially, the effect is temporary and controllable: messenger RNA is rapidly degraded, allowing treatment duration to be adjusted and long-term risks to be minimized.
Many questions remain unanswered. The team plans to test this strategy in other animal models and examine its effects on other immune cells such as B lymphocytes. But the idea is already on the table: instead of fighting aging cell by cell, perhaps the future will be about teaching the body to restore the lost signals of its own immunological youth, at least for a while.
By María Jimena Delgado Díaz
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