Discovering the secret to longevity in mice has the potential to be applied to humans

The naked mole rat (Heterocephalus glaber), which lives in the Horn of Africa and parts of Kenya, has long attracted the attention of scientists because its genome has more in common with humans than with mice, making it an ideal model for studying aging and longevity.

This rodent can live up to 30 years, many times longer than the lifespan of species of the same size.

A new study published in the journal Science shows that four small mutations in the enzyme cGAS (cyclic guanosine monophosphate-adenosine monophosphate synthase) can help mice repair DNA damage more effectively, slowing the aging process.

In humans and mice, this enzyme normally impairs DNA repair.

Accumulation of genetic mutations and DNA damage during cell division is a major cause of aging and age-related diseases, said study co-author Zhiyong Mao, a molecular biologist at Tongji University in Shanghai, China.

Homologous recombination (HR) is a key mechanism for DNA repair, and when it goes wrong, the body is susceptible to cancer or premature aging.

In humans and mice, the cGAS enzyme is often “pulled” away from damaged DNA by another protein, disrupting repair. However, in naked mole rats, the team discovered four specific amino acid substitutions that make cGAS more stable after DNA damage, allowing it to interact with other repair proteins for longer, increasing the cell’s ability to restore genetic material.

When the team removed the cGAS enzyme from mole rat cells using the gene-editing tool CRISPR-Cas9, DNA damage accumulated rapidly.

In contrast, when a version of cGAS carrying four distinct mutations from the mole rat was introduced into fruit flies, these individuals lived significantly longer than flies carrying the normal human cGAS enzyme.

“This study demonstrates a positive role for cGAS in extending lifespan,” said author Mao. “This enzyme may be a potential target for enhancing genome repair in humans.”

Mr. Lindsay Wu, a molecular biologist at the University of New South Wales (Australia), said that the HR mechanism could be the key to slowing down the aging process, but warned that this result is still far from being applied in humans.

He added that the experiments used a human cGAS variant that has been shown to impair the innate immune response – a factor that also contributes to aging.

“The work focuses on DNA repair, but the impact of the inflammatory response to genetic damage needs to be further considered,” he said.

This research opens up new understanding of how nature develops superior cell protection mechanisms, which may help humans in the future find strategies to slow or reverse the aging process./.

(TTXVN/Vietnam+)

Source: https://www.vietnamplus.vn/tim-ra-bi-quyet-truong-tho-o-loai-chuot-co-tiem-nang-ap-dung-tren-nguoi-post1069601.vnp