The naked mole rat, a small underground rodent that lives in Africais known for its extraordinary longevity, which would depend on efficient DNA repair and resides in subtle changes in just four amino acids.
A study led by Tongji University in China, which publishes Science indicates that Evolutionary mutations in cGAS, an innate immune system enzyme that senses DNA to trigger immune responses, may improve the animal’s ability to repair genetic damage related to aging.
However, in other species, such as mice and humans, cGAS can suppress homologous recombination (HR) of DNA, a fundamental pathway for DNA repair, which could promote cancer and shorten life expectancy.
Naked mole rats (Heterocephalus glaber) are exceptionally long-lived rodents, with a maximum life expectancy of nearly 40 years.approximately 10 times more than species of similar size and is very resistant to diseases, it almost never has cancerand cardiac or neurodegenerative ailments.
The genetic composition of this rodent is closer to that of humans than to that of mice, which makes it a valuable model to study the molecular mechanisms underlying the longevity of the species.
A key aspect of longevity is genome stability, but how these animals maintain DNA integrity, particularly through repair mechanisms, remains largely unknown.
1/12 | Giant rats lead landmine detection in Cambodia. Mott Sreymom, 34, a rat trainer with the humanitarian demining organization APOPO, carries a Gambian rat back from a landmine field. – Anton L. Delgado
HR is a critical DNA repair pathway, and defects in that process are linked to premature aging.
In naked mole rats, the team discovered four specific amino acid substitutions in cGAS, allowing the protein to persist longer and at higher levels after DNA damage.
This increased abundance reinforces interactions with key repair factors, enhancing HR repair.
The authors showed that fruit flies genetically modified to express human cGAS, but with the four naked mole rat-specific mutations, lived longer than flies expressing unaltered human cGAS.
The findings suggest that these evolutionary mutations in specific amino acids of the naked mole rat cGAS not only enhance DNA repair, but may also directly contribute to the species’ extraordinary nature.