US EditionTransient hepatic reconstitution of trophic factors enhances aged immunity
MIT and Broad researchers used lipid nanoparticle mRNA to boost T-cell populations and function in aged mice, doubling cytotoxic T cells and improving vaccine and cancer therapy responses.
- This month, MIT and Broad researchers delivered mRNA encoding DLL1, FLT3L, and IL‑7 to 18-month-old mice's livers, reported in Nature and at the American Society of Hematology meeting.
- Thymic involution reduces T‑cell production and diversity, as the thymus shrinks with age and is largely replaced by fatty tissue by age 75; prior hormone treatments and bloodstream growth‑factor approaches have failed or been limited by toxicity and feasibility.
- In 18-month-old mice vaccinated with ovalbumin, the researchers found cytotoxic T-cell numbers doubled after mRNA treatment, with larger T-cell populations and better survival when combined with a PD-L1 checkpoint inhibitor.
- The researchers plan near‑term follow‑up studies in other animal models and to identify more factors affecting B cells, while saying the approach could improve vaccine efficacy and cancer therapy in patients.
- The liver's protein production capacity and blood‑filtering role made it an appealing target; the team repurposed it to secrete thymic signals because hepatocytes uptake mRNA and circulating T cells flow through.
12 Articles
12 Articles
Scientists Discover Protein That Can Rejuvenate the Aging Immune System
A single blood protein can make aging stem cells act young again. As people age and notice changes like graying hair or reduced muscle strength, their immune system also undergoes shifts. One key change involves the stem cells that give rise to blood and immune cells, which can accumulate mutations over time and raise the [...]
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lavozdemichoacan.com.mxAs people age, the capacity of their immune system deteriorates; T-cell populations decrease and cannot react so quickly to pathogens.A new research now shows that it is possible to reverse this from an innovative approach.In particular, the study done in mice reveals that mRNA technology (messenger) can be used to transform the liver into a temporary source of important immune system regulatory factors that are naturally lost during aging.
When we are young, the immune system is a precise mechanism that responds to threats and shuts down. Over the years, neutrophils and monocytes, which give the first response to the invaders, lose mobility and efficiency, and the ability to generate T lymphocytes, which take days to develop because they specifically train against the microorganism or cancer cell that threatens us, decreases. The immune system is disordered and kept on without nee…
Transient hepatic reconstitution of trophic factors enhances aged immunity
Ageing erodes human immunity, in part by reshaping the T cell repertoire, leading to increased vulnerability to infection, malignancy and vaccine failure1–3. Attempts to rejuvenate immune function have yielded only modest results and are limited by toxicity or lack of clinical feasibility1,3–5. Here we show that the liver can be transiently repurposed to restore age-diminished immune cues and improve T cell function in aged mice. These immune cu…
An mRNA cocktail has rejuvenated the immune cells of old mice and strengthened their defences. Can the method make vaccinations and cancer therapies more effective in humans?
New MIT mRNA therapy restores immune defenses lost with age
Immune protection fades with time, and much of that decline traces back to the thymus. This small organ, located in front of the heart, trains new T cells and releases signals that help them survive. As adulthood progresses, the thymus steadily shrinks. This process, called thymic involution, reduces the supply of fresh, naive T cells, narrows the range of T cell receptors and weakens defenses against infections, vaccines and cancer. Older T cel…
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