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Frailty, inflammation and the elderly

  • SI: Frailty, Ageing and Inflammation
  • Published:
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Abstract

Frailty is a term used as a marker of vulnerability, identifying individuals with a diminished capacity to respond to external stressors. Those who are frail are at increased risk of death, institutionalisation and worsening disability. While the associations of frailty with increasing chronological age, female gender, functional dependence and chronic disease are now well described, the aetiology of frailty remains less clearly understood. The growing body of evidence linking inflammation and frailty in older people, an association that seems consistent across different frailty definitions, is therefore of great interest to research gerontologists. However, further studies are needed to establish the exact nature of this relationship. Inflammation may be primarily causal, a compensatory response to viral antigens or subclinical disease or an epi-phenomenon, merely a marker of another key pathophysiological process such as excessive oxidative stress. Furthermore, it has recently been recognised that frailty is most strongly associated with a combination of immunological and physiological impairments rather than a single biomarker. This supports the conceptualisation of ageing as the progressive accumulation of damage to a complex system resulting in aggregate loss of system redundancy. The frail older person is analogous to a complex system without redundancy: capacity to respond to external stressors is reduced. A critical mass of abnormalities across different systems may therefore be a more important determinant of frailty than any individual pathway.

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References

  • Balistreri CR, Colonna-Romano G, Lio D, Candore G, Caruso C (2009) TLR4 polymorphisms and ageing: implications for the pathophysiology of age-related diseases. J Clin Immunol 29:406–415

    Article  CAS  PubMed  Google Scholar 

  • Bandeen-Roche K, Walston JD, Huang Y, Semba RD, Ferrucci L (2009) Measuring systemic inflammatory regulation in older adults: evidence and utility. Rejuvenation Res 12:403–410

    Article  PubMed  Google Scholar 

  • Barbieri M, Ferrucci L, Ragno E, Corsi A, Bandinelli S, Bonafe M, Olivieri F, Giovagnetti S, Franceschi C, Guralnik JM, Paolisso G (2003) Chronic inflammation and the effect of IGF-I on muscle strength and power in older persons. Am J Physiol Endocrinol Metab 284:E481–E487

    CAS  PubMed  Google Scholar 

  • Barzilay JI, Blaum C, Moore T, Xue QL, Hirsch CH, Walston JD, Fried LP (2007) Insulin resistance and inflammation as precursors of frailty: the Cardiovascular Health Study. Arch Intern Med 167(7):635–641

    Article  PubMed  Google Scholar 

  • Cappola AR, Xue QL, Ferrucci L, Guralnik JM, Volpato S, Fried LP (2003) Insulin-like growth factor I and interleukin-6 contribute synergistically to disability and mortality in older women. J Clin Endocrinol Metab 88:2019–2025

    Article  CAS  PubMed  Google Scholar 

  • Carter CS, Hofer T, Seo AY, Leeuwenburgh C (2007) Molecular mechanisms of life- and health-span extension: role of calorie restriction and exercise intervention. Appl Physiol Nutr Metab 32:954–966

    Article  CAS  PubMed  Google Scholar 

  • Cesari M, Penninx BW, Pahor M, Lauretani F, Corsi AM, Rhys Williams G, Guralnik JM, Ferrucci L (2004) Inflammatory markers and physical performance in older persons: the InCHIANTI study. J Gerontol A Biol Sci Med Sci 59:242–248

    PubMed  Google Scholar 

  • De Martinis M, Franceschi C, Monti D, Ginaldi L (2006) Inflammation markers predicting frailty and mortality in the elderly. Exp Mol Pathol 80:219–227

    Article  PubMed  Google Scholar 

  • Ershler WB, Keller ET (2000) Age-associated increased interleukin-6 gene expression, late-life diseases and frailty. Ann Rev Med 51:245–270

    Article  CAS  PubMed  Google Scholar 

  • Ferrucci L, Harris TB, Guralnik JM, Tracy RP, Corti MC, Cohen HJ, Penninx B, Pahor M, Wallace R, Havlik RJ (1999) Serum IL-6 level and the development of disability in older persons. J Am Geriatr Soc 47:639–646

    CAS  PubMed  Google Scholar 

  • Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, Panourgia MP, Invidia L, Celani L, Scurti M, Cevenini E, Castellani GC, Salvioli S (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128:92–105

    Article  CAS  PubMed  Google Scholar 

  • Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA (2001) Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 56:M146–M156

    CAS  PubMed  Google Scholar 

  • Fried LP, Xue QL, Cappola AR, Ferrucci L, Chaves P, Varadhan R, Guralnik JM, Leng SX, Semba RD, Walston JD, Blaum CS, Bandeen-Roche K (2009) Nonlinear multisystem physiological dysregulation associated with frailty in older women: implications for etiology and treatment. J Gerontol A Biol Sci Med Sci 64:1049–1057

    PubMed  Google Scholar 

  • Fulop T, Pawelec G, Castle S, Loeb M (2009) Immunosenescence and vaccination in nursing home residents. Clin Infect Dis 48:443–448

    Article  PubMed  Google Scholar 

  • Gavrilov LA, Gavrilova NS (2006) Reliability theory of aging and longevity. In: Handbook of the biology of aging, 6th edn. Academic Press

  • Greiwe JS, Cheng B, Rubin DC, Yarasheski KE, Semenkovich CF (2001) Resistance exercise decreases skeletal muscle tumor necrosis factor alpha in frail elderly humans. FASEB J 15:475–482

    Article  CAS  PubMed  Google Scholar 

  • Gruenewald TL, Seeman TE, Karlamangla AS, Sarkisian CA (2009) Allostatic load and frailty in older adults. J Am Geriatr Soc 57:1525–1531

    Article  PubMed  Google Scholar 

  • Haddad F, Zaldivar F, Cooper DM, Adams GR (2005) IL-6-induced skeletal muscle atrophy. J Appl Physiol 98:911–917

    Article  CAS  PubMed  Google Scholar 

  • Hammerman D (1999) Toward an understanding of frailty. Ann Intern Med 130:945–950

    Google Scholar 

  • Howard C, Ferrucci L, Sun K, Fried LP, Walston J, Varadhan R, Guralnik JM, Semba RD (2007) Oxidative protein damage is associated with poor grip strength among older women living in the community. J Appl Physiol 103:17–20

    Article  CAS  PubMed  Google Scholar 

  • Hubbard RE, O’Mahony MS, Calver BL, Woodhouse KW (2008) Plasma esterases and inflammation in ageing and frailty. Eur J Clin Pharmacol 64:895–900

    Article  CAS  PubMed  Google Scholar 

  • Hubbard RE, O’Mahony MS, Savva GM, Calver BL, Woodhouse KW (2009) Inflammation and frailty measures in older people. J Cell Mol Med 13(9B):3103–3109

    Article  PubMed  Google Scholar 

  • Hunt KJ, Walsh BM, Voegeli D, Roberts HC (2010) Inflammation in aging part 1: physiology and immunological mechanisms. Biol Res Nurs 11:245–252

    Article  CAS  PubMed  Google Scholar 

  • Kirkwood TB, Finch CE (2002) Ageing: the old worm turns more slowly. Nature 419(6909):794–795

    Article  CAS  PubMed  Google Scholar 

  • Koch S, Larbi A, Ozcelik D, Solana R, Gouttefangeas C, Attig S, Wikby A, Strindhall J, Franceschi C, Pawelec G (2007) Cytomegalovirus infection: a driving force in human T cell immunosenescence. Ann NY Acad Sci 1114:23–35

    Article  CAS  PubMed  Google Scholar 

  • Kotler DP (2000) Cachexia. Ann Int Med 133:622–634

    CAS  PubMed  Google Scholar 

  • Krabbe KS, Pedersen M, Bruunsgaard H (2004) Inflammatory mediators in the elderly. Exp Gerontol 39:687–699

    Article  CAS  PubMed  Google Scholar 

  • Kuller LH (1999) Serum IL-6 and development of disability in older persons. J Am Geriatr Soc 47:755–756

    CAS  PubMed  Google Scholar 

  • LaCroix AZ, Gray SL, Aragaki A, Cochrane BB, Newman AB, Kooperberg CL, Black H, Curb JD, Greenland P, Woods NF, Women’s Health Initiative (2008) Statin use and incident frailty in women aged 65 years or older: prospective findings from the Women’s Health Initiative Observational Study. J Gerontol A Biol Sci Med Sci 63(4):369–375

    PubMed  Google Scholar 

  • Leng SX, Cappola AR, Andersen RE, Blackman MR, Koenig K, Blair M, Walston JD (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 16:153–157

    CAS  PubMed  Google Scholar 

  • Leng SX, Xue Q-L, Tian J, Walston JD, Fried LP (2007) Inflammation and frailty in older women. J Am Geriatr Soc 55:864–871

    Article  PubMed  Google Scholar 

  • Leng SX, Xue QL, Tian J, Huang Y, Yeh SH, 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 44:511–516

    Article  PubMed  Google Scholar 

  • Maggio M, Guralnik JM, Longo DL, Ferrucci L (2006) Interleukin-6 in aging and chronic disease: a magnificent pathway. J Gerontol Med Sci 61:575–584

    Google Scholar 

  • McEwen B, Seeman T (2009) Allostatic load and allostasis. MacArthur Research Network on SES and Health. http://www.macses.ucsf.edu/research/allostatic/allostatic.php. Accessed June 2010

  • McEwen BS, Stellar E (1993) Stress and the individual. Mechanisms leading to disease. Arch Intern Med 153:2093–2101

    Article  CAS  PubMed  Google Scholar 

  • Morley JE (2008) Diabetes, sarcopenia, and frailty. Clin Geriatr Med 24:455–469

    Article  PubMed  Google Scholar 

  • Puts MT, Visser M, Twisk JW, Deeg DJ, Lips P (2005) Endocrine and inflammatory markers as predictors of frailty. Clin Endocrinol 63:403–411

    Article  CAS  Google Scholar 

  • Reid MB, Li YP (2001) Tumor necrosis factor-alpha and muscle wasting: a cellular perspective. Respir Res 2:269–272

    Article  CAS  PubMed  Google Scholar 

  • Rockwood K (2007) Why geriatric medicine? In: Rai S, Mulley G (eds) Elderly medicine: a training guide, 2nd edn. Taylor & Francis, London

    Google Scholar 

  • Rockwood K, Mitnitski A (2007) Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci 62:722–727

    PubMed  Google Scholar 

  • Rolland Y, Czerwinski S, Abellan Van Kan G, Morley JE, Cesari M, Onder G, Woo J, Baumgartner R, Pillard F, Boirie Y, Chumlea WM, Vellas B (2008) Sarcopenia: its assessment, etiology, pathogenesis, consequences and future perspectives. J Nutr Health Aging 12:433–450

    Article  CAS  PubMed  Google Scholar 

  • Schmaltz HN, Fried LP, Xue QL, Walston J, Leng SX, Semba RD (2005) Chronic cytomegalovirus infection and inflammation are associated with prevalent frailty in community-dwelling older women. J Am Geriatr Soc 53:747–754

    Article  PubMed  Google Scholar 

  • Semba RD, Margolick JB, Leng S, Walston J, Ricks MO, Fried LP (2005) T cell subsets and mortality in older community-dwelling women. Exp Gerontol 40:81–87

    Article  CAS  PubMed  Google Scholar 

  • Serviddio G, Romano AD, Greco A, Rollo T, Bellanti F, Altomare E, Vendemiale G (2009) Frailty syndrome is associated with altered circulating redox balance and increased markers of oxidative stress. Int J Immunopathol Pharmacol. 22:819–827

    CAS  PubMed  Google Scholar 

  • Szanton SL, Allen JK, Seplaki CL, Bandeen-Roche K, Fried LP (2009) Allostatic load and frailty in the women’s health and aging studies. Biol Res Nurs 10:248–256

    Article  CAS  PubMed  Google Scholar 

  • Toth MJ, Matthews DE, Tracy RP, Previs MJ (2005) Age-related differences in skeletal muscle protein synthesis: relation to markers of immune activation. Am J Physiol Endocrinol Metab 288:E883–E891

    Article  CAS  PubMed  Google Scholar 

  • van den Biggelaar AH, Huizinga TW, de Craen AJ, Gussekloo J, Heijmans BT, Frölich M, Westendorp RG (2004) Impaired innate immunity predicts frailty in old age. The Leiden 85-plus study. Exp Gerontol 39:1407–1414

    Article  PubMed  Google Scholar 

  • Walston J, McBurnie MA, Newman A, Tracy RP, Kop WJ, Hirsch CH, Gottdiener J, Fried LP (2002) Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study. Arch Intern Med 162:2333–2341

    Article  PubMed  Google Scholar 

  • Walston J, Fedarko N, Yang H, Leng S, Beamer B, Espinoza S, Lipton A, Zheng H, Becker K (2008) The physical and biological characterization of a frail mouse model. J Gerontol A Biol Sci Med Sci 63:391–398

    PubMed  Google Scholar 

  • Wang GC, Kao WH, Murakami P, Xue QL, Chiou RB, Detrick B, McDyer JF, Semba RD, Casolaro V, Walston JD, Fried LP (2010) Cytomegalovirus infection and the risk of mortality and frailty in older women: a prospective observational cohort study. Am J Epidemiol 171:1144–1152

    Article  PubMed  Google Scholar 

  • Wikby A, Nilsson BO, Forsey R, Thompson J, Strindhall J, Löfgren S, Ernerudh J, Pawelec G, Ferguson F, Johansson B (2006) The immune risk phenotype is associated with IL-6 in the terminal decline stage: findings from the Swedish NONA immune longitudinal study of very late life functioning. Mech Ageing Dev 127:695–704

    Article  CAS  PubMed  Google Scholar 

  • Williams FM, Wynne H, Woodhouse KW, Rawlins MD (1989) Plasma aspirin esterase: the influence of old age and frailty. Age Ageing 18:39–42

    Article  CAS  PubMed  Google Scholar 

  • Wu IC, Shiesh SC, Kuo PH, Lin XZ (2009) High oxidative stress is correlated with frailty in elderly chinese. J Am Geriatr Soc 57:1666–1671

    Article  PubMed  Google Scholar 

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Correspondence to Ruth E. Hubbard.

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Hubbard, R.E., Woodhouse, K.W. Frailty, inflammation and the elderly. Biogerontology 11, 635–641 (2010). https://doi.org/10.1007/s10522-010-9292-5

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