The ‘late-life’ genes that wake up during mid-life crises

As we hit middle age, we are more prone to stress.

We have full-time jobs, kids to put through school, and maybe even elderly parents to take care of.

But a new study has found a subset of genes that only become active later in life to protects us from strenuous events.

They are part of a unique stress-response mechanism that was previously unknown, scientists say, which is specifically designed for ageing adults. 

However, research also suggests these middle-aged genes could be woken up earlier, by extreme stress or disrupting your sleeping pattern – accelerating ageing symptoms.  

A subset of genes called ‘late-life cyclers’ have been discovered in a new study. They become active only as we age and respond to the extreme stresses we face

This group of genes, whose rhythmic activity late in life had not previously been understood, were named ‘late-life cyclers’, or LLCs, by former Oregon State University graduate student and lead author of the study, Rachael Kuintzle. 

At least 25 such genes become rhythmic with age, and the function of some of them remains unclear. 

‘This class of LLC genes appear to become active and respond to some of the stresses most common in aging, such as cellular and molecular damage, oxidative stress, or even some disease states,’ said co-author Professor Jadwiga Giebultowicz of the OSU College of Science.   

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The study, conducted at OSU, used fruit flies in the experiment, since they share 75 percent of disease-prone genes with humans. 

The researchers created artificial oxidative stress, which damages brain membranes. 

They found that while young flies express certain stress-response genes weakly or not at all, the older flies expressed these LLC genes rhythmically and robustly.

‘Aging is associated with neural degeneration, loss of memory and other problems, which are exacerbated if clock function is experimentally disrupted,’ said Professor Giebultowicz, an international expert on the mechanisms and function of the biological clock.

‘The LLC genes are part of the natural response to that, and do what they can to help protect the nervous system.’

The increased, rhythmic expression of these genes during times of stress, scientists said, are another example of just how biologically important circadian rhythms are, because they help to regulate the activity of hundreds of genes essential to the processes of life.

And as aging brings with it a host of new problems, the LLC genes become more and more active.

The researchers explained that some of these same genes are known to be more active in people who have cancer and described them as a ‘double-edged sword’ – necessary during times of stress but possibly harmful if activated all the time.

According to Dr David Hendrix, an assistant professor in the OSU College of Science and College of Engineering, and co-author on the study, some LLC genes are known to play roles in isolating improperly ‘folded’ proteins or helping them refold. 

This could help prevent formation of proteins that can lead to age-related neurodegeneration.

‘Discovery of LLC genes may provide a missing link, the answer to why the disruption of circadian clocks accelerates aging symptoms,’ Dr Hendrix said.

The discovery of these genes may also provide a missing link to understanding our circadian clocks – the cycle which tells our bodies when to sleep, rise, and eat.

When these clocks are disrupted by doing night shifts or sleeping too little, aging symptoms are accelerated. Although it has never been understood why, scientists now suggest these genes may be the answer.

The study showed that intense stress at any point in life can cause some of the LLC genes to spring into action.

Circadian clocks, or rhythm, is linked to the light–dark cycle, or how many hours of day or night there are. They allow us to anticipate and prepare for precise and regular environmental changes such as when to eat and sleep. 

Found throughout the nervous system and peripheral organs these ‘clock genes’ even play a role in DNA repair, fertility and the effectiveness of medications. 

People with routine disruptions of their circadian rhythms have been shown to have a shorter lifespan and be more prone to cancer.