Growing old stressfully: chronic stress and prematurely aged cells

Human chromosomes showing telomeres
Human chromosomes (grey) capped by telomeres (white). Photograph: public domain

Forty years ago, the Whitehall Study of men working for Britain’s Civil Service famously revealed that those at the bottom of the pecking order were much more likely to die prematurely than those at the top – regardless of other risk factors such as smoking. They had higher mortality rates from all causes, but especially heart disease.

So the lowly paid doorman, whether or not he was a heavy smoker, was more likely to drop dead than the clerk sitting at his desk all day earning more money. As ever, life was deeply unfair. But what was the biological explanation for this health inequality? One theory was that the stress and lack of control over their working lives experienced by men in lowlier jobs were putting their health at risk, though how that worked physiologically was anyone’s guess.

The body’s reaction to acute stress – the fight-or-flight response – equips us to deal with sudden threats to our survival by releasing adrenaline and cortisol, which among other things raise blood pressure, heart rate and blood sugar levels. But sustained or chronic stress is harmful to health, increasing the risk of depression, weight gain and heart disease.

Since the 1980s, scientists at University College London have been following up the Whitehall Study to find out how stress at work leads to poorer health, and their latest study reveals that older men whose bodies have trouble returning to normal after a stressful event show the hallmarks of accelerated cellular ageing – which could put them at greater risk of heart disease. The men who had this faulty stress response and signs of cellular ageing were also more likely to lack social support and score highly on measures of pessimism and hostility.

The research involved 333 healthy men and women, aged between 54 and 76. As proxies for cell ageing, the researchers measured the length of telomeres – the protective caps on the ends of chromosomes that get worn down whenever a cell divides – in their immune cells. They also measured the activity of telomerase, which is the enzyme responsible for repairing telomeres.

In older cells that have been through many cycles of division, the telomeres may be worn away to such an extent that the cell stops dividing and becomes “senescent”, or even undergoes apoptosis or “cell suicide”. Shortened telomeres have been linked to many age-related diseases, so they’re often used as a marker of cellular ageing.

The study was designed to monitor the participants’ physiological stress responses. They were also given psychological tests to assess their levels of social and emotional support, optimism and hostility. In addition, they were asked about adverse events early in their life, such as the death of a parent or sibling.

The volunteers were given a couple of standardised tasks that put them under mental stress. One involved using a metal stylus to trace a star, which could only be seen as a mirror image. Every time the stylus strayed from the outline of the star the apparatus emitted a loud beep and a mistake was registered. To raise the tension further, participants were told the “average person” could complete five circuits of the star in the allotted time.

The scientists took blood and saliva samples before and after the stressful tasks. Blood pressure, heart rate and heart rate variability were also monitored while the tasks were carried out and then at 40 and 70-minute intervals afterwards.

As expected, the stressful tasks led to increases in heart rate and blood pressure, and a reduction in heart rate variability in all the participants. They also raised levels of the stress hormone cortisol in saliva, and blood levels of molecules involved in inflammation.

What was surprising was that in men with short telomeres and high telomerase activity, these stress responses took longer to return to normal. In addition, these men scored higher for hostility, had less social support in their lives, and were less optimistic. Their mothers were also more likely to have died before they were 16.

The associations still held even after the men’s body mass index, age and socioeconomic status were taken into account.

All this suggests that an inability to handle stress, perhaps as a result of a difficult early life and lack of social support in adulthood, can accelerate cell ageing. It may also help explain why stressful work and a perceived lack of control are associated with poor health and increased mortality rate, regardless of other health risks such as body weight and increasing age.
It’s worth noting that the men were all outwardly healthy, but the evidence of accelerated ageing in their cells suggests they will be more prone to ill health in the coming years.

The associations were not seen in women, however. The authors are at a loss to explain this, but speculate that oestrogen – which boosts telomerase activity – may have protected the women’s telomeres in their younger years.

The results are reported this week in the journal Proceedings of the National Academy of Sciences (pdf).

The researchers suggest that shorter telomeres reflect the cumulative “allostatic load” or wear-and-tear caused by chronic stress, which can lead to high blood pressure, weight gain and heart disease. The cells they studied were immune cells, so there’s also a possibility there was age-related damage to the immune system as well.

They conclude that elevated allostatic load predicts the risk of early death and functional decline at older ages. “Our study suggests that these processes could be mediated through accelerated cellular ageing.”

• This article was first published on the Guardian’s Notes & Theories blog

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