Ageing, physical function, and the diurnal rhythms of cortisol and dehydroepiandrosterone

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Summary

The present study examined the relationship between ageing, physical function and the diurnal rhythms of cortisol and dehydroepiandrosterone (DHEA). Participants were 36 community dwelling older adults aged between 65 and 86 years old. Salivary cortisol and DHEA were measured over the course of one day: immediately upon awakening, 30 min later, and then 3 h, 6 h, 9 h and 12 h post-awakening. Participants completed the Nottingham extended activities of daily living index, the Berg Balance Scale and their handgrip strength was assessed. Older participants had a significantly higher cortisol area under the curve (AUC), lower overall DHEA levels, lower DHEA AUC, a decreased diurnal slope of decline and increased cortisol:DHEA ratio. Lower diurnal cortisol levels were associated with poorer performance on the Berg Balance Scale and lower handgrip strength, and those with a flattened DHEA diurnal profile reported less independence in carrying out daily tasks. These associations withstood adjustment for age. In conclusion, this study suggests an association between cortisol, DHEA, ageing and physical function.

Introduction

Cortisol and dehydroepiandrosterone (DHEA) are stress hormones of the hypothalamic–pituitary–adrenal (HPA) axis. Cortisol is involved in a number of important functions including responses to stress, energy metabolism, vascular activity, and inflammatory and immune responses (Schürmeyer and Wickings, 1999). DHEA is a precursor to sex hormones; it has been proposed to affect various systems of the body and be anti-ageing (Chahal and Drake, 2007) and immune enhancing (Buford and Willoughby, 2005). Cortisol exhibits a marked diurnal rhythm, characterised by a rapid increase in levels upon awakening peaking at around 30 min post-awakening and declining to reach a nadir in the evening, where DHEA has been shown to display a flat pattern of secretion after waking followed by a progressive decline to 3 h post-awakening with no significant change thereafter (Pruessner et al., 1997).

Previous studies examining the effects of ageing on diurnal cortisol secretion have yielded conflicting results, with either a flattening of the diurnal pattern of secretion with increasing age (VanCauter et al., 1996, Deuschle et al., 1997, Yen and Laughlin, 1998, Luz et al., 2003), no association (Edwards et al., 2001b, Wolf et al., 2002), or decreased overall levels (Orentreich et al., 1992, Straub et al., 2000) with age. Therefore, it is possible that cortisol per se may not increase with ageing, but rather that cortisol levels are high in relation to other hormones such as DHEA, which declines with age in both saliva (Ahn et al., 2007) and serum (Belanger et al., 1994, Labrie et al., 1997). This would lead to an overrepresentation of cortisol and an increase in the cortisol:DHEA ratio (Phillips et al., 2007), which has been found to be associated with immune impairments and infection risk in older adults (Butcher et al., 2005).

In comparison to cortisol, little attention has been paid to the diurnal pattern of DHEA in ageing individuals or across a range of ages among older adults, with one exception, which found similar profiles in young and older individuals (Erosheva et al., 2002). However, alterations in the diurnal rhythm of DHEA, as well as cortisol, and the cortisol:DHEA ratio are particularly relevant for ageing individuals where changes in endocrine function may relate to disturbances in other physiological systems, and consequently the presentation of physical frailty (Walston et al., 2006).

Frailty has become increasingly recognised as a key concern for older individuals (Cherniack et al., 2007). How frailty should be defined has been subject to much deliberation. However, it has been proposed that frailty is characterised by a diminished ability to carry out activities of daily living, both practically and socially (Rockwood et al., 1994, Brown et al., 1995). Dependence on others for activities of daily living is a predictor of admission to an institution, home care use, admission to and prolonged stays in hospital, and mortality rates Rockwood et al. (1994). Alternatively, other criteria can also be used as indicators of deterioration in physical function: for example, handgrip strength, walking speed (Fried et al., 2001) and balance (Brown et al., 2000); falling due to poor balance is a key predictor of hospital admission and progression to frailty (Donaldson et al., 1990). These variables can be used separately as markers of physical function, or in combination to create a frailty index.

Neuroendocrine and immune dysregulation has also been recognised as a manifestation of frailty (Ahmed et al., 2007) and may additionally be a pathway to its onset and development (Joseph et al., 2005, Walston et al., 2006). Therefore, changes in physical function, prior to frailty onset and development, could also potentially also be associated with changes in the endocrine system. Higher cortisol levels in older adults have been associated with characteristics of frailty in several studies (Peeters et al., 2007, Varadhan et al., 2008). Further, low levels of serum DHEA sulphate (DHEA-S) have been negatively associated with a frailty phenotype (Voznesensky et al., 2009) and poorer physical function (Berkman et al., 1993). However, less is known about DHEA in its un-sulphated form and DHEA in saliva in relation to frailty. As previously mentioned, DHEA displays a diurnal variation where DHEA-S does not (Kroboth et al., 1999), and the diurnal rhythm of DHEA has been shown to be important for health and well being. For example, blunted levels of DHEA in the morning has been previously associated with depression (Goodyer et al., 1996) stress and anxiety (Luz et al., 2003), and therefore may relate to other aspects of health, such as physical function. To our knowledge, previous research has not employed multiple sampling points across the day; therefore the diurnal rhythm of DHEA has not been examined in relation to physical function in older adults. Further, the advantages of employing saliva sampling, rather than serum sampling, to analyse both cortisol (Kirschbaum and Hellhammer, 1994) and DHEA (Granger et al., 1999) have been highlighted previously.

Given the scant research on cortisol and DHEA and particularly their rhythms in relation to physical function in older adults, the present study investigated the diurnal rhythms of cortisol and DHEA and the cortisol:DHEA ratio in relation to age among older adults. It also examined how these endocrine parameters related to physical function among older adults. It was hypothesised that those indicating lower levels of physical function would exhibit flatter diurnal profiles of cortisol and DHEA.

Section snippets

Participants

Participants were 36 (18 women) community dwelling older adults aged between 65 and 86 years (mean = 72.5, SD = 6.47), with mean BMI of 26.7 (SD = 4.73). Forty one participants were originally recruited, five were excluded for non compliance and/or extreme (≥±3 SD from the mean) hormone values. Older adults were recruited from clubs and associations in Birmingham, UK, and through posters displayed in businesses around the local area. The majority (94%) of participants described themselves as “white”,

Results

Participants mean cortisol and DHEA levels overall and at each time point are shown in Table 1, along with their mean handgrip strength, Berg Balance Scale and ADL scores.

Diurnal cortisol, DHEA and ageing

Participants aged 72–86 showed higher diurnal cortisol levels and a higher AUC. This elevation in diurnal cortisol with ageing is consistent with previous findings; however, it has mainly been observed as a result of higher evening and nocturnal concentrations (VanCauter et al., 1996, Deuschle et al., 1997), as opposed to the higher daytime levels in the present study. VanCauter et al. (1996) and Deuschle et al. (1997) measured cortisol in plasma, thus the different specimen of measurement may

Role of the funding source

This study was funded via a University of Birmingham School Studentship to J. Heaney.

Conflict of interest

The authors have no conflicts of interest.

Acknowledgements

The authors would like to thank all of the participants in this research study.

References (56)

  • S.R. Kunz-Ebrecht et al.

    Differences in cortisol awakening response on work days and weekends in women and men from the Whitehall II cohort

    Psychoneuroendocrinology

    (2004)
  • C. Luz et al.

    Impact of psychological and endocrine factors on cytokine production of healthy elderly people

    Mech. Ageing Dev.

    (2003)
  • C.R. Parker

    Dehydroepiandrosterone and dehydroepiandrosterone sulfate production in the human adrenal during development and aging

    Steriods

    (1999)
  • J.C. Pruessner et al.

    Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change

    Psychoneuroendocrinology

    (2003)
  • J.C. Pruessner et al.

    Free cortisol levels after awakening: a reliable biological marker for the assessment of adrenocortical activity

    Life Sci.

    (1997)
  • J.M. Smyth et al.

    Individual differences in the diurnal cycle of cortisol

    Psychoneuroendocrinology

    (1997)
  • R.H. Straub et al.

    Cytokines and hormones as possible links between endocrinosenescence and immunosenescence

    J. Neuroimmunol.

    (2000)
  • G.-L.S. Whembolua et al.

    Bacteria in the oral mucosa and its effects on the measurement of cortisol, dehydroepiandrosterone, and testosterone in saliva

    Horm. Behav.

    (2006)
  • O.T. Wolf et al.

    Salivary cortisol day profiles in elderly with mild cognitive impairment

    Psychoneuroendocrinology

    (2002)
  • S.S.C. Yen et al.

    Aging and the adrenal cortex

    Exp. Gerontol.

    (1998)
  • E. Aardal et al.

    Cortisol in saliva – reference ranges and relation to cortisol in serum

    Eur. J. Clin. Chem. Clin. Biochem.

    (1995)
  • R.S. Ahn et al.

    Salivary cortisol and DHEA levels in the Korean population: age-related differences, diurnal rhythm, and correlations with serum levels

    Yonsei Med. J.

    (2007)
  • A. Belanger et al.

    Changes in serum concentrations of conjugated and unconjugated steriods in 40-year-old to 80-year-old men

    J. Clin. Endocrinol. Metab.

    (1994)
  • K.O. Berg et al.

    Clinical and laboratory measures of postural balance in an elderly population

    Arch. Phys. Med. Rehabil.

    (1992)
  • K.O. Berg et al.

    The berg balance scale: reliability with elderly residents and patients with an acute stroke

    Scand. J. Rehabil. Med.

    (1995)
  • I. Brown et al.

    Frailty: constructing a common meaning, definition and conceptual framework

    Int. J. Rehabil. Res.

    (1995)
  • M. Brown et al.

    Physical and performance measures for the identification of mild to moderate frailty

    J. Gerontol. A Biol. Sci. Med. Sci.

    (2000)
  • T.W. Buford et al.

    Impact of DHEA(S) and cortisol on immune function in ageing: a brief review

    Appl. Physiol. Nutr. Metabol.

    (2005)
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