The bare mole rat is known for residing practically 10x longer than different mammals of comparable measurement.
| Photograph Credit score: Tim Evanson
The bare mole rat (Heterocephalus glaber) is a small, hairless rodent native to East Africa, and well-known for residing an astonishingly very long time, as much as round 37 years, practically 10x longer than mammals of comparable measurement. Scientists have lengthy suspected its exceptional longevity comes from diversifications that maintain its DNA intact.
As we age, DNA injury accumulates in our cells. Usually cells restore these breaks utilizing a number of molecular pathways, however errors or inefficiencies in restore make genomes unstable and result in ageing and illness.
One molecule recognized to affect this course of is cyclic GMP-AMP synthase (cGAS). In people and mice, cGAS helps detect international DNA, corresponding to that from viruses, and triggers immune responses. Nevertheless, it additionally suppresses one of many physique’s major DNA-repair programs, known as homologous recombination. In consequence, human cGAS can truly make cells extra liable to ageing and most cancers.
Scientists have questioned whether or not, throughout evolution, the bare mole rat might need modified cGAS in order that it now not interferes with DNA restore, or perhaps even helps it. A brand new examine led by researchers at Tongji College, and not too long ago revealed in Science, got down to verify this concept.
The researchers in contrast the cGAS genes and proteins of bare mole rats with these of people and mice. They used genetic engineering instruments to change particular amino acids — the constructing blocks of proteins — between species and observe the results on DNA restore. Additionally they carried out experiments in cell cultures, fruit flies, and mice to check how these molecular adjustments affected genome stability, mobile ageing, and lifespan.
Thus the crew discovered that in people and mice, cGAS interferes with the homologous recombination pathway — however in bare mole rats cGAS enhances it. The rationale lay in 4 amino acid substitutions in cGAS’s construction, which allowed bare mole rat cGAS to stay sure to DNA for longer after injury occurred as a substitute of being shortly eliminated. This binding prevented cGAS from being tagged for destruction by a course of known as ubiquitination.
As a substitute, bare mole rat cGAS introduced collectively two restore proteins, known as FANCI and RAD50, to hurry up homologous recombination and assist repair DNA breaks extra effectively. Cells with this modified cGAS confirmed fewer indicators of stress-induced ageing.
When the scientists put the identical 4 amino acid adjustments into human cGAS, the molecule stopped harming DNA restore.
The invention is exceptional for exhibiting that longevity can evolve not solely by bettering useful restore enzymes but in addition by weakening dangerous regulators. Within the bare mole rat, evolution primarily ‘flipped’ the position of cGAS, supporting the long-standing concept that environment friendly DNA restore is among the major defenses towards ageing.
“Our work supplies a molecular foundation for the way DNA restore is activated to contribute to the distinctive longevity throughout evolution in bare mole-rats,” the researchers wrote of their paper.
Unbiased specialists have mentioned that if scientists can safely reproduce this impact in different species, together with people, it may open new paths for age-related analysis and therapies. For instance, medicines that regulate how cGAS interacts with DNA would possibly assist cells keep genome integrity with out compromising the immune system.
Printed – October 13, 2025 06:00 am IST
