This work sits off on its own: almost nobody nearby, with the closest neighbor at a distance of 0.496. Around it lie studies of epigenetic clocks, cellular aging and protein evolution. What sets this paper apart is that it links aging to a specific chemical modification of transfer RNA that depends on the microbiome. Until now, aging has been described through the accumulation of DNA damage or changes in the epigenome, but the role of protein synthesis accuracy has remained underappreciated.
The scientists measured queuine levels in the blood of rats and humans of different ages using mass spectrometry. They then added queuine to the food of Drosophila flies and mice and tracked lifespan, physical activity and cognitive function. To understand the mechanism, they isolated transfer RNA from tissues and analyzed its modifications, and also studied the activity of genes and proteins in cells with altered queuine levels.
Queuine levels in rat blood fell from 18.22 ng/ml at 6 months to 8.83 ng/ml at 36 months, and in people over 60 it was 65% lower than in 30-40-year-olds. Queuine supplementation extended median lifespan in flies by 47.46% and mean lifespan in mice by 15.3%. The mice also showed better memory, coordination and grip strength, and their biological age according to epigenetic clocks dropped by 4.72 months. The manQ modification in transfer RNA disappeared in old animals but was restored after queuine intake.
The work shows that the accuracy of protein synthesis is a controllable factor in aging, not just a consequence of it. Queuine acts as a "microbial vitamin," linking gut health to molecular processes inside cells. This sets it apart from neighboring studies that focus on genetic or epigenetic mechanisms. The discovery offers a new target for geroprotective interventions aimed at restoring translation accuracy.
The field could move toward studying how the microbiome influences aging through other RNA modifications. Designer probiotics that produce queuine may emerge, or personalized diets to maintain its levels. It also remains to be determined which codons suffer from the loss of manQ and how this relates to age-related diseases.
The results could influence gerontology, nutrition science and microbiome research. They open a path to developing queuine-based supplements to slow aging.
Clinical trials of queuine in humans are needed to assess safety and efficacy. It is also important to study long-term effects and possible side effects.
The work links aging to a loss of accuracy in protein synthesis, one of the key problems in gerontology. It offers a concrete mechanism through which the microbiome can influence health in old age.
Queuine was discovered in the 1970s, but its role in aging has only now been figured out. It is named after the letter Q, which stands for its precursor in the genetic code.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.