Growing old stressfully: chronic stress and prematurely aged cells ...

http://www.theguardian.com/science/blog/2014/mar/13/growing-o...

Growing old stressfully: chronic

stress and prematurely aged cells
Apparently healthy older men who have poor social support networks and
abnormal physiological responses to stress show signs of accelerated cell
ageing
James Kingsland
Thursday 13 March 2014 07.00GMT

Forty years ago, the Whitehall Study of men working for Britains 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 anyones guess.
The bodys reaction to acute stress the ght-or-ight 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 nd out how stress at work leads
to poorer health, and their latest study reveals that older men whose

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Growing old stressfully: chronic stress and prematurely aged cells ...

http://www.theguardian.com/science/blog/2014/mar/13/growing-o...

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 theyre 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 ve 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
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Growing old stressfully: chronic stress and prematurely aged cells ...

http://www.theguardian.com/science/blog/2014/mar/13/growing-o...

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 inammation.
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 mens 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 dicult 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.
Its 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 womens 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 reect 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 theres 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
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Growing old stressfully: chronic stress and prematurely aged cells ...

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