'Later-life' genes activated during stress

Researchers have found a set of bodyclock-controlled genes that activate in later life and times of intense stress to protect the body.

These 'late-life cycling' (LLC) genes appear to protect against the stresses associated with ageing and disease. This unique stress-response mechanism may help explain why disrupting the biological clock accelerates ageing.

'Ageing is associated with neural degeneration, loss of memory and other problems,' said Professor Jadwiga Giebultowicz of Oregon State University (OSU), co-senior author on the study. 'The LLC genes are part of the natural response to that, and do what they can to help protect the nervous system.'

Important biological processes are controlled by daily circadian rhythms or the 'biological clock' – the 24-hour cycle in living beings which turns gene expression on and off in sync. People with a disrupted biological clock have been found to have problems such as a shorter lifespan and be more prone to cancer.

The study compared the activity of genes in young and old fruit flies. Researchers noted that as flies aged, some clock-controlled genes maintained their rhythm while others drifted out of sync.

Unexpectedly, 25 genes became active and rhythmic with age – many of which proteins were related to protective stress-responses. These genes could only be activated in younger flies under extreme biological stress.

'This class of LLC genes appear to become active and respond to some of the stresses most common in ageing, such as cellular and molecular damage, oxidative stress, or even some disease states,' said Professor Giebultowicz. Some of these genes are known to be more active in people who have cancer.

The study's results, published in Nature Communications, 'are surprising, because the conventional wisdom in the field based on studies of mammals and human subjects is that circadian rhythms weaken with ageing,' Professor Michael Nitabach, of Yale University who was not involved in the study, told The Scientist.

The results suggest that as organisms age or undergo intense stress, the biological clock shifts priority to stress-protecting responses.

Some of the LLC genes are known to help isolate or refold badly formed proteins. This may help prevent the build-up of toxic protein aggregates which can lead to neurodegeneration.

'Discovery of LLC genes may provide a missing link, the answer to why the disruption of circadian clocks accelerates ageing symptoms,' said Dr David Hendrix, of OSU and senior co-author.

Biological clock genes are found throughout the nervous system and peripheral organs. The clock regulates many important processes including sleep, DNA repair, fertility and metabolism.

Further research into this new group of genes may expand our understanding of ageing and possibly provide new avenues of study to help protect the nervous system.