Image courtesy of Jannissimo/Shutterstock
Joel Kontinen
Why do naked mole rats live for so long? It may be to a
thing that intelligent design has provided.
The
longevity of naked mole rats may partly be due to them having a variant of a
key protein that boosts DNA repair – a discovery that could help extend our own
lives.
Naked mole
rats live for up to 37 years – far longer than other rodents their size. What
is the secret of their longevity? Among other factors, it could be down to a
variant of an immune protein that boosts DNA repair
The
discovery might lead to therapies that extend human lifespans, say Zhiyong Mao at Tongji University in
Shanghai, China. It is also another piece of evidence supporting the idea that
the accumulation of mutations – that is, the failure to repair damaged DNA – is
one of the main causes of ageing.
The immune
protein in question, called cGAS, is found in many animals. Its main function
is thought to be to sound the alarm when it detects DNA outside the nucleus of
a cell, which could be a sign of cancer or a viral attack.
But cGAS is
also found in the nucleus of cells. In humans and mice, it has been shown to
suppress DNA repair, increasing the mutation rate and the risk of
cancer. Exactly why is unclear – it could be an undesirable side effect rather
than an evolved function.
Mao’s team
has now shown that the version of cGAS found in naked mole rats has the
opposite effect in the nucleus, actually boosting DNA repair. This is due to
differences in four of the amino acids that make up the cGAS protein. If these
four amino acids are altered in mole rat cells, the animal’s cGAS no longer
boosts DNA repair. Conversely, if these are changed in the human version of
cGAS, the protein no longer inhibits DNA repair.
What’s
more, when the team genetically engineered fruit flies to produce the naked
mole rat version of cGAS, they lived for nearly 70 days, compared with around
60 days for unmodified flies.
So could
making human cells produce the naked mole rat cGAS extend our lives? “Yes, gene
editing and mRNA delivery could be potential ways to improve DNA repair and
promote longevity in humans,” says Mao. But getting enough of the key cells in
our bodies to produce the modified cGAS wouldn’t be easy, he says.
Another
approach could be to find small-molecule drugs that interact with the human
cGAS protein and make it behave like the mole rat one, says Mao.
The study
does indeed suggest that cGAS influences lifespan, says Vera Gorbunova at the University of
Rochester, New York, whose team has shown that a molecule called
hyaluronic acid also contributes to the long lives of naked mole rats. “[So]
modulating the activity of cGAS by pharmacological or genetic means can have
beneficial effects on health and lifespan,” she says.
Michael Le Page 2025
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