Tick clock, stay ahead of the aging clock

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Summary: Aging in humans (and animals) be either an inevitable process of wear and tear or as an inherent biological program by which the lifespan of each species is predetermined.

Recent research has shown that DNA methylation, an epigenetic modification which alters how DNA is read and expressed without altering the underlying sequence, can show age-related changes.  A subset of these modifications is so accurate that chronological age in humans can be predicted +/- 3.6 years from any tissue or fluid in the body. This is by far the best biomarker of age available and is referred to as the epigenetic clock.  Interestingly, analysis of DNA methylation can also provide information on biological age, which is a measure of how well your body functions compared to your chronological age. For instance, people suffering from the fatty liver disease have a faster ticking clock, while centenarians have a slower clock.

Researchers at the Babraham Institute and the European Bioinformatics Institute have now identified a mouse epigenetic aging clock. The work published in Genome Biology shows that changes in DNA methylation at 329 sites in the genome are predictive of age in the mouse with an accuracy of +/- 3.3 weeks. Considering that humans live to approx. 85 years and mice for 3 years, the accuracy of the mouse and human clocks are surprisingly similar.

Resetting the clock:

Using the mouse model, researchers showed that lifestyle interventions known to shorten lifespan sped up the clock.

For example, Removal of ovaries in female mice accelerates the clock, a phenomenon observed in early menopause women. Interestingly, a high-fat diet usually known as hazardous to health also accelerates the aging clock. Researchers were able to detect changes to the epigenetic clock as early as 9 weeks of age, bearing in mind that the lifespan of a mouse can easily be more than 3 years, this represents a massive reduction in time and cost which the researchers believe will accelerate future aging discoveries.

The identification of human epigenetic clock has been a breakthrough in the study of aging. However, there is number of questions about its conservation, mechanism and its function. Discovery of mouse epigenetic clock is exciting because it suggests that this clock may be a fundamental and conserved feature of mammalian aging.

Researchers have shown that we can detect changes to the ticking rate in response to changes, such as diet, therefore in the future, we will be able to determine the mechanism and function of this epigenetic clock and use it to improve human health.”

With further study, scientists will be able to understand the inner mechanistic workings of such a clock (for example using knowledge about enzymes that regulate DNA methylation in the genome) and change its ticking rate in the mouse model. This will reveal whether the clock is causally involved in aging, or whether it is a read-out of other underlying physiological processes. These studies will also suggest approaches to wind the aging clock back to rejuvenate tissues or even a whole organism.