HPA axis

A unique opportunity to study the regulation of cortisol - the stress hormone - and its affect on ageing.

Prof Yoav Ben-Shlomo and Dr Mike Gardner introduce HPA Axis
See more on the MRC comms Youtube channel

The hypothalamic-pituitary-adrenal (HPA) axis is part of the endocrine system, the body’s own mechanism to regulate various important processes through the secretion of hormones. The hypothalamus at the base of the brain links the brain to the endocrine system. One of these pathways results in the production of cortisol (a stress hormone). This hormone shows diurnal variation, that is the levels vary over 24 hours with high levels in the morning and low levels at night. There is also an increase in levels with wakening in the morning.

What does the HPA axis have to do with ageing?

Evidence so far indicates that the HPA axis contributes to biological ageing. In older animals there is a delayed return to normal after stressful events and a corresponding higher level of cortisol. As animals get older, the normal negative feedback inhibition (i.e. high levels result in reducing further cortisol release) may become disrupted due to neuronal loss in the brain. Early life exposures to stress may alter how the HPA axis reacts to ongoing stress later in life - by increasing the resting level of cortisol in the body. So there may be a connection between early life experiences and aspects of ageing such as cognitive decline later in life.

How will this study advance our knowledge of the HPA axis and ageing?

Much of the research on the HPA axis comes from animal studies so we did not know whether these findings applied to humans. Research about cortisol in humans was often based on small samples and was usually based on measurement at one time point (cross-sectional). Some studies, but not all, have shown an association with higher cortisol and worse memory or physical performance. Four of the HALCyon cohorts have taken cortisol measures with one study having two measures over a twenty year period. By pooling the results from these and other studies we have been able to test whether ageing traits are associated with different diurnal patterns of cortisol in a larger number of people than ever before.

What we are researching

HPA pathways

We have looked to see:

  • Whether age related changes in the HPA axis were associated with changes in capability and wellbeing. Towards this end we undertook the first study examining the relationship between repeat cortisol mesures (over 20 years) and physical capability in later life.
  • Whether HPA functionality over the life course is affected by gender, socioeconomic and other demographic factors.
  • Whether there are any genetic markers that can be used to measure and predict HPA functionality.

What have we found so far?

  • We reported that dysregulation in the HPA axis (as indicated by higher night-time cortisol and a smaller diurnal drop) is associated with worse physical performance (i.e. slower walking speed and poorer balance) in later life among older men participating in the Caerphilly Prospective study (Gardner et al., International Journal of Epidemiology 2011).
  • In meta-analyses using data from six cohorts (four HALCyon cohorts plus Whitehall II and LASA), we found that a more dynamic HPA axis, best measured by greater diurnal decline, was associated with faster walking speed and better chair rise times among participants aged 50-92y. However, there was no strong evidence of associations with grip strength or standing balance (Gardner et al,.Psychoneuroendocrinology 2013).

Please see the Case for Support for a detailed, more technical overview of the work packages.

Further Reading

HALCyon Publications

Kuh D, Cooper R, Hardy R, Richards M, Ben-Shlomo Y (Eds). A life course approach to healthy ageing. Oxford University Press to be published January 9th 2014.

  • Chapter 10: A life course approach to neuroendocrine systems: the example of the HPA axis
    Professor Yoav Ben-Shlomo, Dr Mike Gardner and Professor Stafford Lightman