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THE BRAIN AGED MORE SLOWLY IN MONKEYS GIVEN A CHEAP DIABETES DRUG  
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Max Kozlov
September 12, 2024
Nature [[link removed]]

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_ A daily dose of the common medication metformin preserved cognition
and delayed decline of some tissues _

,

 

A low-cost diabetes drug slows ageing in male monkeys and is
particularly effective at delaying the effects of ageing on the brain
[[link removed]], finds a small
study that tracked the animals for more than three years1
[[link removed]]. The
results raise the possibility that the widely used
medication, metformin [[link removed]],
could one day be used to postpone ageing in humans.

Monkeys that received metformin daily showed slower age-associated
brain decline
[[link removed]] than did those
not given the drug. Furthermore, their neuronal activity resembled
that of monkeys about six years younger (equivalent to around 18 human
years) and the animals had enhanced cognition and preserved liver
function.

This study, published in _Cell_ on 12 September, helps to suggest
that, although dying is inevitable, “ageing, the way we know it, is
not”, says Nir Barzilai, a geroscientist at the Albert Einstein
College of Medicine in New York City, who was not involved in the
study.

Medicine-cabinet staple

Metformin has been used for more than 60 years to lower blood-sugar
levels in people with type 2 diabetes
[[link removed]] — and is the
second most-prescribed medication in the United States. The drug has
long been known to have effects beyond treating diabetes
[[link removed]], leading
researchers to study it against conditions such as cancer,
cardiovascular disease and ageing.

Reversal of biological clock restores vision in old mice
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Data from worms, rodents, flies and people who have taken the drug for
diabetes suggest the drug might have anti-ageing effects. But its
effectiveness against ageing had not been tested directly in primates,
and it is unclear whether its potential anti-ageing effects are
achieved by lowering blood sugar or through a separate mechanism.

This led Guanghui Liu, a biologist who studies ageing at the Chinese
Academy of Sciences in Beijing, and his colleagues to test the drug on
12 elderly male cynomolgus macaques (_Macaca fasciucularis_); another
16 elderly monkeys and 18 young or middle-aged animals served as a
control group. Every day, treated monkeys received the standard dose
of metformin that is used to control diabetes in humans. The animals
took the drug for 40 months, which is equivalent to about 13 years for
humans.

Over the course of the study, Liu and his colleagues took samples from
79 types of the monkeys’ tissues and organs, imaged the animals’
brains and performed routine physical examinations. By analysing the
cellular activity in the samples, the researchers were able to create
a computational model to determine the tissues’ ‘biological
age’, which can lag behind or exceed the animals’ age in years
since birth [[link removed]].

Slowing the clock

The researchers observed that the drug slowed the biological ageing of
many tissues, including from the lung, kidney, liver, skin and the
brain’s frontal lobe. They also found that it curbed chronic
inflammation, a key hallmark of ageing
[[link removed]]. The study was
not intended to see whether the drug extended the animals’
lifespans; previous research has not established an impact on
lifespan2
[[link removed]] but has
shown lengthened healthspan3
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number of years an organism lives in good health.

This means that metformin can “effectively rewind organ age” in
monkeys, Liu says. The authors also identified a potential pathway by
which the drug protects the brain: it activates a protein called NRF2,
which safeguards against cellular damage triggered by injury and
inflammation.

This study is the “most quantitative, thorough examination of
metformin action that I’ve seen beyond mice”, says Alex Soukas, a
molecular geneticist at Massachusetts General Hospital in Boston.
“It was a surprise to see how comprehensive [the drug’s] effects
were across tissue types.”

Low-cost drug, high-cost trial

Although these results are encouraging, much more research will be
necessary to study the drug before it’s validated as an anti-ageing
compound in humans, Liu says.

The fraught quest to account for sex in biology research
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For one, only 12 monkeys received the drug. Soukas says he would
therefore like to see a replication of this effort or a study that
includes more animals. Furthermore, the researchers tested only male
animals, which Rafael de Cabo, a translational geroscientist at the
National Institute on Aging in Baltimore, Maryland, says is
concerning. He acknowledges that it is extremely expensive to run this
type of long-term experiment, but adds that it is crucial to
understand ageing in females as well, given that there are often
large differences between the sexes
[[link removed]].

In the meantime, Liu and his colleagues have launched a 120-person
trial [[link removed]] in collaboration
with the biopharmaceutical company Merck in Darmstadt, Germany, which
developed and manufactures metformin, to test whether the drug delays
ageing in humans.

Barzilai has even bigger ambitions: he and his colleagues have been
spearheading an effort to raise US$50 million to study the drug in a
trial of 3,000 people aged 65–79 over 6 years. Research into
metformin and other anti-ageing candidates could one day mean that
doctors will be able to focus more on keeping people healthy for as
long as possible rather than on treating diseases, he says.

_doi: [link removed]

References

*
Yang, Y. _et al._ Cell [link removed]
(2024). Article
[[link removed]] Google Scholar
[[link removed].] 

*
Mohammed, I., Hollenberg, M. D., Ding, H. & Triggle, C. R. _Front.
Endocrinol._ 12, 718942 (2021). Article
[[link removed]] Google Scholar
[[link removed].] 

*
Martin-Montalvo, A. _et al._ _Nature Commun._ 4, 2192
(2013). Article [[link removed]] PubMed
[[link removed]] Google
Scholar
[[link removed].]

* Science
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* biology
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* aging
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