Researchers have believed changes to a body’s DNA – called mutations – are a leading cause of ageing.
But a team from Boston’s Harvard Medical School has found support for an alternative hypothesis: it is the changes that affect the expression of the DNA – called epigenetics – that affect ageing.
The scientists, whose study was published in the journal Cell, demonstrated this via a mouse model where changes in epigenetic information caused mice to first age and then reverse ageing.
Gene activity (the ‘switch on’ and ‘switch off’ of genes) is associated with epigenetic changes – chemical changes in the DNA that do not alter the DNA sequence. Epigenetics studies how the environment can modify how genes work, without actually changing the genes themselves.
Examples of factors that may lead to epigenetic changes include diet, ageing, physical activity, obesity, tobacco and alcohol use, environmental pollutants, stress, infections and diseases like cancer.
The study’s senior author Professor David Sinclair explained that previous research he had been involved with in the 1990s showed lifespan is under the control of epigenetic regulators called sirtuins (a family of signalling proteins involved in metabolic regulation).
‘We have discovered that if you turn on 3 ‘Yamanaka’ genes that normally switch on during embryogenesis (formation and development of an embryo), you can safely reverse the ageing process by more than 50%,’ he told medicalnewstoday.com.
‘These genes initiate a program not well understood, but the outcome is age reversal and restoration of tissue function. For example, we can reverse the age of optic nerves to restore the vision of all mice.’
During the latest study, researchers created temporary, fast-healing ‘cuts’ in the DNA of mice; these imitated the effect of certain lifestyle and environmental effects on the DNA’s epigenetic pattern.
The cuts caused the mice’s epigenetic pattern to change and eventually malfunction, causing the mice to begin looking and acting older. These mice also had increased biomarkers indicating ageing,
The scientists then gave these mice gene therapy to reverse the epigenetic changes, which they found ‘reset’ the mice’s epigenetic program and ultimately reversed the ageing the mice had experienced.
‘We hope these results are seen as a turning point in our ability to control ageing,’ said Professor Sinclair. ‘This is the first study showing we can have precise control of the biological age of a complex animal; that we can drive it forwards and backward at will.’
California neurological researcher Dr Santosh Kesari told medicalnewstoday.com this was a ‘very exciting study,’ opening up understanding of how ageing occurs and how we can measure it at the DNA level.
‘It turns out it’s not just that we accumulate mutations in the DNA, which we think is one of the main factors that cause age-related disorders, but more how the DNA is read that is really contributing to ageing. And as we age, reading of the DNA is affected in a big way.
This really opens up a new way of thinking about ageing, but also a new way to think about targeting ageing by developing drugs that affect how the cell reads the DNA.’
