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DNA ageing reversed in mice

27 March 2017

By Dr Linda Wijlaars

Appeared in BioNews 894

Scientists have reversed ageing in mice by adding a chemical involved in DNA repair to their drinking water.

They plan to trial the substance in humans and say that it could be used to stop ageing, cancer and could also be used to prevent DNA damage during radiation treatment.

'The cells of the old mice were indistinguishable from the young mice after just one week of treatment,' said lead author Professor David Sinclair of the University of New South Wales, Australia. 'This is the closest we are to a safe and effective anti-ageing drug that's perhaps only three to five years away from being on the market, if the trials go well.'

During the natural ageing process there is a decrease in DNA repair activity, which causes errors in the DNA pile up as cells divide, leading to a loss of cell function. The research team observed that the concentration of nicotinamide adenine dinucleotide (NAD+) – a chemical first discovered over a century ago – in cells also declines with age.

Using human embryonic kidney cells, they found that NAD+ binds to a protein that had previously been implicated in cancer (DBC1), which in turn can bind to another protein (PARP1), blocking it from performing DNA repair. As NAD+ levels decrease with age, fewer DBC1 proteins are bound to it, leaving DBC1 to block PARP1 and DNA repair.

The team went on to test whether restoring NAD+ levels would also reverse this ageing process in mice. They added a NAD+ precursor, NMN, to the drinking water of old and young mice and found that the NAD+ levels increased dramatically in the livers of old mice compared with untreated old mice. Markers for DNA damage also decreased.

'Our results unveil a key mechanism in cellular degeneration and ageing, but beyond that they point to a therapeutic avenue to halt and reverse age-related and radiation-induced DNA damage,' said Professor Sinclair. 

He has co-founded MetroBiotech, a company that is developing a human-grade version of NMN – a naturally occurring compound found in small amounts in foods like broccoli, cucumber, avocado and edamame – and plans to test its safety in 25 people in the next six months.

He says that, if it proves safe, it could be used to protect people from radiation damage, including astronauts and pilots exposed to high levels of cosmic radiation. 'The idea is to protect the body from radiation exposure here on earth, either naturally occurring or doctor-inflicted,' he told Time magazine. 'If I were going to have an X-ray or a CT scan, I would take NMN beforehand.'

SOURCES & REFERENCES
Science | 24 March 2017
 
The Australian | 24 March 2017
 
Time | 23 March 2017
 
Science Daily (press release) | 23 March 2017
 
Harvard Medical School News | 23 March 2017
 

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