Medical researchers have found a cause of
ageing in animals that can be reversed, possibly paving the way for new
treatments for age-related diseases including cancer, type 2 diabetes, muscle
wasting and inflammatory diseases.
The researchers hope to start human trials
late next year.
The study, which is published today in the
journal Cell, relates to mitochondria, which are our cells' battery packs and
give energy to carry out key biological functions.
The work, led by UNSW Medicine's David
Sinclair, found a series of molecular events enable communication inside cells
between the mitochondria and the nucleus. As communication breaks down, ageing
"The ageing process we discovered is
like a married couple – when they are young, they communicate well, but over
time, living in close quarters for many years, communication breaks down,"
says UNSW Professor Sinclair, who is based at Harvard Medical School.
"And just like a couple, restoring
communication solved the problem," says the geneticist.
is known so far?
The background to the research is that as
we age, levels of the chemical NAD, which starts this communication cascade,
decline. Until now, the only way to slow the NAD drop was to restrict calories
and exercise intensively. In this work, the researchers used a compound that
cells transform into NAD to repair the broken network and rapidly restore
communication and mitochondrial function. It mimics the effects of diet and
While Professor Sinclair's group in Boston
was working on muscles in tissue culture, colleagues at UNSW in Sydney were
working on animal models to prove the work could have the same results.
"It was shocking how quickly it
happened," says co-author Dr Nigel Turner, an ARC Future Fellow from
UNSW's Department of Pharmacology. "If the compound is administered early
enough in the ageing process, in just a week, the muscles of the older mice
were indistinguishable from the younger animals."
The mice, which were two-years-old, also
performed well on insulin resistance and inflammation – both of which are
correlated with ageing. They were compared with six-month-old animals.
"It was a very pronounced
effect," says Dr Turner. "It's something like a 60-year-old being
similar to a 20-year-old on some measures."
The younger mice given the same compound
were "supercharged above normal level" on certain measures, according
to Dr Turner. "So it is possible this would have benefits in healthy,
One particularly important aspect of this
research involves HIF-1, which is an intrusive molecule that foils
communication, but also has a role in cancer.
It has been known for some time that HIF-1
is switched on in many cancers, now this research has found it also switches on
"We become cancer-like in our ageing
process," says Professor Sinclair. "Nobody has linked cancer and
ageing like this before." This may explain why the greatest risk of cancer
The researchers are now looking at the
longer-term outcomes the NAD-producing compound has on mice. They are exploring
whether it can be used to safely treat rare mitochondrial diseases and other
conditions, such as type 1 and type 2 diabetes, as well as for longevity and
Professor Sinclair and his group have been
studying the fundamental science of ageing for many years, primarily focusing
on a group of genes called sirtuins. Previous studies from his lab had shown
that one of these genes, SIRT1, was activated by the naturally occurring
compound resveratrol (found in small amounts in grapes, red wine and certain
The latest research goes further, as it
activates all seven of the sirtuin genes.
"There's clearly much more work to be
done here, but if those results stand, then ageing may be a reversible
condition, if it is caught early," says Professor Sinclair.
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