DNA communication 'key to ageing'

A previously hidden cause of ageing has been reversed by scientists, causing muscle tissue to appear decades younger.

613b4482-68b8-11e3-8220-0a0c0223000020131220T100954
How DNA relates to the ageing process is linked to communication, according to scientists

A previously hidden cause of ageing has been reversed by scientists, causing muscle tissue to appear decades younger.

The molecular pathway they uncovered is also thought to play a key role in many cancers that afflict older people.

Although conducted in mice, the ground-breaking research focuses on an ageing process that has never before been described and may have far-reaching implications for human health.

It involves communication between DNA in the cell nucleus, which contains the vast majority of our genes, and mitochondria, the tiny powerhouses in cells that generate energy.

Mitochondria house a genetic code, or genome, all of their own made up of DNA that lies outside the nucleus.

Scientists have long known that mitochondria are involved in ageing but the role played by communication between the two DNA centres has only now been revealed.

By reconnecting broken links between the nucleus and mitochondria, the researchers caused muscle tissue of two-year old mice to resemble that of six-month-old animals.

In human terms, this is the equivalent of transforming 60-year-old muscles into those of a 20-year-old.

"The ageing process we discovered is like a married couple," said lead scientist Professor David Sinclair, from Harvard Medical School in the US. "When they are young they communicate well but over time, living in close quarters for many years, communication breaks down. And just like with a couple, restoring communication solved the problem.

"There's clearly much more work to be done here, but if these results stand then many aspects of ageing may be reversible if caught early."

Many age-related problems are believed to be caused by genetic defects in mitochondria. Because such mutations cannot be reversed, scientists have generally been sceptical about the idea of turning back the ageing clock.

Prof Sinclair's team found that damaged mitochondrial genes were only part of the story. To a large extent, cells remained healthy as long as their nuclear and mitochondrial genomes were in sync.

The scientists discovered that with age, chemical changes occur that cause the cross-genome communication to become disrupted. This in turn damages the mitochondria, reducing the cell's ability to generate energy and leading to signs of ageing and disease.

A natural molecule, called NAD, was found to be critical to this process. As levels of NAD decline with age, damage to the communication channels increases.

By treating mice with a chemical compound that cells transform into NAD, the researchers were able to repair the broken network, restoring communication and mitochondrial function.

If the compound was administered early enough, before large numbers of genetic mutations had accumulated in the mitochondria, key aspects of ageing could be reversed.

Just one week of treatment rejuvenated the muscles of the ageing mice, as demonstrated by measurements of insulin resistance, inflammation and wasting.

Another key aspect of the findings, published in the journal Cell, involved a molecule called HIF-1 which is chiefly responsible for the cellular communication breakdown.

The molecule is also thought to help cancers survive and grow.

"It's certainly significant to find that a molecule that switches on in many cancers also switches on during ageing," said co-author Dr Ana Gomes who works in Prof Sinclair's laboratory.

"We're starting to see now that the physiology of cancer is in certain ways similar to the physiology of ageing. Perhaps this can explain why the greatest risk of cancer is age."

The scientists are now looking at the long-term effects of inducing NAD production in mice to see if it can increase their healthy lifespans. They are also exploring whether the same NAD-creating compound can be used to treat rare mitochondrial diseases, or common metabolic disorders such as diabetes.

Tim Spector, professor of genetic epidemiology at King's College London, said: " This is an intriguing and exciting finding that some aspects of the ageing process are reversible.

"It is however a long and tough way to go from these nice mouse experiments to showing real anti-ageing effects in humans without side effects."