Abstract
Frailty is a multidimensional geriatric syndrome characterised by a state of increased vulnerability to disease. Its causes are unclear, limiting opportunities for intervention. Age-related changes to the immune-endocrine axis are implicated. This study investigated the associations between the immune-endocrine axis and frailty as well as mortality 10 years later among men and women aged 65 to 70 years. We studied 254 participants of the Hertfordshire Ageing Study at baseline and 10-year follow-up. At baseline, they completed a health questionnaire and had collection of blood samples for immune-endocrine analysis. At follow-up, Fried frailty was characterised and mortality ascertained. Higher baseline levels of differential white cell counts (WCC), lower levels of dehydroepiandosterone sulphate (DHEAS) and higher cortisol:DHEAS ratio were all significantly associated with increased odds of frailty at 10-year follow-up. Baseline WCC and cortisol:DHEAS clearly discriminated between individuals who went on to be frail at follow-up. We present the first evidence that immune-endocrine biomarkers are associated with the likelihood of frailty as well as mortality over a 10-year period. This augments our understanding of the aetiology of frailty, and suggests that a screening programme at ages 60–70 years could help to identify individuals who are at high risk of becoming frail and who would benefit from early, targeted intervention, for example with DHEA supplementation or anti-inflammatory strategies. Progress towards the prevention of frailty would bring major health and socio-economic benefits at the individual and the population level.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Avila-Funes JA, Helmer C, Amieva H, Barberger-Gateau P, Le GM, Ritchie K et al (2008) Frailty among community-dwelling elderly people in France: the three-city study. J Gerontol A Biol Sci Med Sci 63(10):1089–1096
Bauer JM, Sieber CC (2008) Sarcopenia and frailty: a clinician’s controversial point of view. Exp Gerontol 43(7):674–678
Buford TW, Willoughby DS (2008) Impact of DHEA(S) and cortisol on immune function in aging: a brief review. Appl Physiol Nutr Metab 33(3):429–433
Cawthon PM, Marshall LM, Michael Y, Dam TT, Ensrud KE, Barrett-Connor E et al (2007) Frailty in older men: prevalence, progression, and relationship with mortality. J Am Geriatr Soc 55(8):1216–1223
Curnow SJ, Falciani F, Durrani OM, Cheung CM, Ross EJ, Wloka K et al (2005) Multiplex bead immunoassay analysis of aqueous humor reveals distinct cytokine profiles in uveitis. Invest Ophthalmol Vis Sci 46(11):4251–4259
De MM, Franceschi C, Monti D, Ginaldi L (2006) Inflammation markers predicting frailty and mortality in the elderly. Exp Mol Pathol 80(3):219–227
Franceschi C, Bonafe M, Valensin S, Olivieri F, De LM, Ottaviani E et al (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254
Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J et al (2001) Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 56(3):M146–M156
Grimm RH Jr, Neaton JD, Ludwig W (1985) Prognostic importance of the white blood cell count for coronary, cancer, and all-cause mortality. JAMA 254(14):1932–1937
Hunt KJ, Walsh BM, Voegeli D, Roberts HC (2010) Inflammation in aging part 1: physiology and immunological mechanisms. Biol Res Nurs 11(3):245–252
Kenny AM, Boxer RS, Kleppinger A, Brindisi J, Feinn R, Burleson JA (2010) Dehydroepiandrosterone combined with exercise improves muscle strength and physical function in frail older women. J Am Geriatr Soc 58(9):1707–1714
Ko FC (2011) The clinical care of frail, older adults. Clin Geriatr Med 27(1):89–100
Lauretani F, Russo CR, Bandinelli S, Bartali B, Cavazzini C, Di IA et al (2003) Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia. J Appl Physiol 95(5):1851–1860
Leng SX, Cappola AR, Andersen RE, Blackman MR, Koenig K, Blair M et al (2004) Serum levels of insulin-like growth factor-I (IGF-I) and dehydroepiandrosterone sulfate (DHEA-S), and their relationships with serum interleukin-6, in the geriatric syndrome of frailty. Aging Clin Exp Res 16(2):153–157
Leng SX, Xue QL, Tian J, Walston JD, Fried LP (2007) Inflammation and frailty in older women. J Am Geriatr Soc 55(6):864–871
Leng SX, Xue QL, Tian J, Huang Y, Yeh SH, Leng SX, Xue QL, Tian J, Huang Y, Fried LP (2009) Associations of neutrophil and monocyte counts with frailty in community-dwelling disabled older women: results from the Women’s Health and Aging Studies I. Exp Gerontol 44(8):511–516
Liu CK, Fielding RA (2011) Exercise as an intervention for frailty. Clin Geriatr Med 27(1):101–110
Lizcano F, Rodriguez JS (2011) Thyroid hormone therapy modulates hypothalamo-pituitary-adrenal axis. Endocr J 58(2):137–142
Parle JV, Maisonneuve P, Sheppard MC, Boyle P, Franklyn JA (2001) Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study. Lancet 358(9285):861–865
Phillips AC, Burns VE, Lord JM (2007) Stress and exercise: getting the balance right for aging immunity. Exerc Sport Sci Rev 35(1):35–39
Phillips AC, Carroll D, Gale CR, Lord JM, Arlt W, Batty GD (2010) Cortisol, DHEA sulphate, their ratio, and all-cause and cause-specific mortality in the Vietnam Experience Study. Eur J Endocrinol 163(2):285–292
Puts MT, Visser M, Twisk JW, Deeg DJ, Lips P (2005) Endocrine and inflammatory markers as predictors of frailty. Clin Endocrinol (Oxf) 63(4):403–411
Syddall H, Roberts HC, Evandrou M, Cooper C, Bergman H, Aihie SA (2010a) Prevalence and correlates of frailty among community-dwelling older men and women: findings from the Hertfordshire Cohort Study. Age Ageing 39(2):197–203
Syddall HE, Simmonds SJ, Martin HJ, Watson C, Dennison EM, Cooper C et al (2010b) Cohort profile: The Hertfordshire Ageing Study (HAS). Int J Epidemiol 39(1):36–43
Thijs L, Fagard R, Forette F, Nawrot T, Staessen JA (2003) Are low dehydroepiandrosterone sulphate levels predictive for cardiovascular diseases? A review of prospective and retrospective studies. Acta Cardiol 58(5):403–410
van Abellan KG, Rolland Y, Bergman H, Morley JE, Kritchevsky SB, Vellas B (2008) The I.A.N.A. Task Force on frailty assessment of older people in clinical practice. J Nutr Health Aging 12(1):29–37
Voznesensky M, Walsh S, Dauser D, Brindisi J, Kenny AM (2009) The association between dehydroepiandosterone and frailty in older men and women. Age Ageing 38(4):401–406
Walston J, McBurnie MA, Newman A, Tracy RP, Kop WJ, Hirsch CH et al (2002) Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study. Arch Intern Med 162(20):2333–2341
Zofkova I, Hill M (2008) Biochemical markers of bone remodeling correlate negatively with circulating TSH in postmenopausal women. Endocr Regul 42(4):121–127
Acknowledgements
This work was funded by the Medical Research Council, the Biotechnology and Biological Sciences Research Council and the University of Southampton.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Baylis, D., Bartlett, D.B., Syddall, H.E. et al. Immune-endocrine biomarkers as predictors of frailty and mortality: a 10-year longitudinal study in community-dwelling older people. AGE 35, 963–971 (2013). https://doi.org/10.1007/s11357-012-9396-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11357-012-9396-8