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Inflammatory Markers and Frailty

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Handbook on Immunosenescence

Abstract

As the aging population increases rapidly worldwide, caring for frail older adults has become the mandate of modern medicine. As such, frailty has been increasingly recognized as an important geriatric syndrome. This is further supported by the recent development of an operational definition, validation of a set of criteria, and evidence for its syndromic nature. Frailty is characterized by decreased functional and physiologic reserve, increased vulnerability to stressors, as well as high risk for serious adverse health outcomes including disability, dependency, and mortality. Although the pathogenesis of this syndrome is far from being elucidated, frail older adults demonstrate dysregulations in multiple physiologic systems. As discussed elsewhere in this handbook, low grade, chronic systemic inflammation manifested in older adults, so-called “inflamm-aging,” is an important feature of immunosenescence. Activation of the inflammation system marked by elevated levels of inflammatory markers, above and beyond age-related increases, is considered the most prominent pathophysiological feature of frailty. This chapter provides an overview of the syndrome of frailty and its relationship with several molecular and cellular inflammatory markers, including interleukin-6 (IL-6), C-reactive protein (CRP), and white blood cell (WBC) and its specific subpopulations. It also discusses the potential role of chronic systemic inflammation, directly and/or through other intermediary systems, in the pathogenesis of frailty.

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References

  1. Fried LP, Tangen C, Walston J et al (2001) Frailty in older adults: Evidence for a phenotype. J Gerontol A Biol Sci Med Sci 56A(3):M1–M11

    Google Scholar 

  2. Fried LP, Walston J (2007) Frailty. In: Halter JB (ed) Hazzard’s Principles of Geriatric Medicine and Gerontology, 6th edn. Anne Arbor, McGraw-Hill

    Google Scholar 

  3. Fried LP, Hadley EC, Walston JD et al (2005) From bedside to bench: research agenda for frailty. Sci Aging Knowledge Environ (31):e24

    Google Scholar 

  4. Walston J, Hadley EC, Ferrucci L et al (2006) Research agenda for frailty in older adults: toward a better understanding of physiology and etiology: summary from the American Geriatrics Society/National Institute on Aging Research Conference on Frailty in Older Adults. J Am Geriatr Soc 54(6):991–1001

    Article  PubMed  Google Scholar 

  5. Lipsitz LA (2002) Dynamics of stability: the physiologic basis of functional health and frailty. J Gerontol A Biol Sci Med Sci 57(3):115–125

    Google Scholar 

  6. Fried LP, Ferrucci L, Darer J et al (2004) Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol A Biol Sci Med Sci 59(3):255–263

    PubMed  Google Scholar 

  7. Bandeen-Roche K, Xue QL, Ferrucci L et al (2006) Phenotype of frailty: characterization in the women’s health and aging studies. J Gerontol A Biol Sci Med Sci 61(3):262–266

    PubMed  Google Scholar 

  8. Woods NF, LaCroix AZ, Gray SL et al (2005) Frailty: emergence and consequences in women aged 65 and older in the Women’s Health Initiative Observational Study. J Am Geriatr Soc 53(8):1321–1330

    Article  PubMed  Google Scholar 

  9. Corapi KM, McGee HM, Barker M (2006) Screening for frailty among seniors in clinical practice. Nat Clin Pract Rheumatol 2(9):476–480

    Article  PubMed  Google Scholar 

  10. Strandberg TE, Pitkala KH (2007) Frailty in elderly people. Lancet 21;369(9570):1328–1329

    Article  Google Scholar 

  11. Avila-Funes JA, Helmer C, Amieva H (2007) Frailty among community-dwelling elderly people in France: the three-city study. J Gerontol

    Google Scholar 

  12. Rockwood K, Andrew M, Mitnitski A (2007) A comparison of two approaches to measuring frailty in elderly people. J Gerontol A Biol Sci Med Sci 62(7):738–743

    PubMed  Google Scholar 

  13. Franceschi C, Bonafe M, Valensin S et al (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254

    Article  PubMed  CAS  Google Scholar 

  14. 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

    Article  CAS  Google Scholar 

  15. Roubenoff R, Parise H, Payette HA et al (2003) Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham Heart Study. Am J Med 15;115(6):429–435

    Article  CAS  Google Scholar 

  16. Bruunsgaard H, Ladelund S, Pedersen AN et al (2003) Predicting death from tumour necrosis factor-alpha and interleukin-6 in 80-year-old people. Clin Exp Immunol 132(1):24–31

    Article  PubMed  CAS  Google Scholar 

  17. Di IA, Ferrucci L, Sparvieri E et al (2003) Serum IL-1beta levels in health and disease: a population-based study. ‘The In CHIANTI study’. Cytokine 21;22(6):198–205

    Google Scholar 

  18. Appay V, Rowland-Jones SL (2002) Premature ageing of the immune system: the cause of AIDS? Trends Immunol 23(12):580–585

    Article  PubMed  CAS  Google Scholar 

  19. Tracy RP (2003) Emerging relationships of inflammation, cardiovascular disease and chronic diseases of aging. Int J Obes Relat Metab Disord 27(Suppl 3):S29–S34

    Article  PubMed  Google Scholar 

  20. Ershler WB (1993) Interleukin-6: a cytokine for gerontologists. J Am Geriatr Soc 41(2): 176–181

    PubMed  CAS  Google Scholar 

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

    PubMed  Google Scholar 

  22. Ershler WB, Keller ET (2000) Age-associated increased interleukin-6 gene expression, latelife diseases, and frailty. Annu Rev Med 51:245–270

    Article  PubMed  CAS  Google Scholar 

  23. Ferrucci L, Harris TB, Guralnik JM et al (1999) Serum IL-6 level and the development of disability in older persons [see comments]. J Am Geriatr Soc 47(6):639–646

    PubMed  CAS  Google Scholar 

  24. Harris TB, Ferrucci L, Tracy RP et al (1999) Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med 106(5):506–512

    Article  PubMed  CAS  Google Scholar 

  25. Cohen HJ, Pieper CF, Harris T et al (1997) The association of plasma IL-6 levels with functional disability in community-dwelling elderly. J Gerontol A Biol Sci Med Sci 52(4):201–208

    Google Scholar 

  26. Taaffe DR, Harris TB, Ferrucci L et al (2000) Cross-sectional and prospective relationships of interleukin-6 and C-reactive protein with physical performance in elderly persons: MacArthur studies of successful aging. J Gerontol A Biol Sci Med Sci 55(12):M709–M715

    PubMed  CAS  Google Scholar 

  27. Reuben DB, Cheh AI, Harris TB et al (2002) Peripheral blood markers of inflammation predict mortality and functional decline in high-functioning community-dwelling older persons. J Am Geriatr Soc 50(4):638–644

    Article  PubMed  Google Scholar 

  28. Visser M, Pahor M, Taaffe DR et al (2002)Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study. J Gerontol A Biol Sci Med Sci 57(5):M326–M332

    PubMed  Google Scholar 

  29. Ferrucci L, Penninx BW, Volpato S et al (2002) Change in muscle strength explains accelerated decline of physical function in older women with high interleukin-6 serum levels. J Am Geriatr Soc 50(12):1947–1954

    Article  PubMed  Google Scholar 

  30. Leng S, Chaves P, Koenig K, Walston J (2002) Serum interleukin-6 and hemoglobin as physiological correlates in the geriatric syndrome of frailty: a pilot study. J Am Geriatr Soc 50(7):1268–1271

    Article  PubMed  Google Scholar 

  31. Leng S, Yang H, Walston J (2004) Decreased Cell Proliferation and Altered Cytokine Production in Frail Older Adults. Aging Clin Exp Res 16:249–252

    PubMed  CAS  Google Scholar 

  32. Leng SX, Xue QL, Tian J et al (2007) Inflammation and frailty in older women. J Am Geriatr Soc 55(6):864–871

    Article  PubMed  Google Scholar 

  33. Schmaltz HN, Fried LP, Xue QL et al (2005) Chronic cytomegalovirus infection and inflammation are associated with prevalent frailty in community-dwelling older women. J Am Geriatr Soc 53(5):747–754

    Article  PubMed  Google Scholar 

  34. Tillet W, Francis T (1930) Serological reactions in pneumonia with a non-protein somatic fraction of pneumococcus. J Exp Med 52:561–571

    Article  Google Scholar 

  35. Hage FG, Szalai AJ (2007) C-reactive protein gene polymorphisms, C-reactive protein blood levels, and cardiovascular disease risk. J Am Coll Cardiol 18;50(12):1115–1122

    Article  CAS  Google Scholar 

  36. Walston J, McBurnie MA, Newman A et al (2002) Frailty and activation of the inflammation and coagulation systems with and without clinical morbidities: Results from the Cardiovascular Health Study. Arch Intern Med 162:2333–2341

    Article  PubMed  Google Scholar 

  37. Puts MT, Visser M, Twisk JW et al (2005 October) Endocrine and inflammatory markers as predictors of frailty. Clin Endocrinol (Oxf) 63(4):403–411

    Google Scholar 

  38. Leng SX, Xue QL, Huang Y et al (2005) Baseline total and specific differential white blood cell counts and 5-year all-cause mortality in community-dwelling older women. Exp Gerontol 40(12):982–987

    Article  PubMed  Google Scholar 

  39. Margolis KL, Manson JE, Greenland P et al (2005) Leukocyte count as a predictor of cardiovascular events and mortality in postmenopausal women: the Women’s Health Initiative Observational Study. Arch Intern Med 14;165(5):500–508

    Article  Google Scholar 

  40. Ruggiero C, Metter EJ, Cherubini A et al (2007) White blood cell count and mortality in the Baltimore Longitudinal Study of Aging. J Am Coll Cardiol 8;49(18):1841–1850

    Article  Google Scholar 

  41. Leng S, Xue QL, Huang Y et al (2005) Total and differential white blood cell counts and their associations with circulating interleukin-6 levels in community-dwelling older women. J Gerontol A Biol Sci Med Sci 60(2):195–199

    Article  PubMed  CAS  Google Scholar 

  42. Semba RD, Margolick JB, Leng S et al (2005) T cell subsets and mortality in older community-dwelling women. Exp Gerontol 40(1–2):81–87

    Article  PubMed  CAS  Google Scholar 

  43. Liu R, Paxton WA, Choe S et al (1996) Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 9;86(3):367–377

    CAS  Google Scholar 

  44. Loetscher P, Uguccioni M, Bordoli L et al (1998) CCR5 is characteristic of Th1 lymphocytes. Nature 391(6665):344–345

    Article  PubMed  CAS  Google Scholar 

  45. Qin S, Rottman JB, Myers P et al (1998) The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. J Clin Invest 15;101(4):746–754

    Article  CAS  Google Scholar 

  46. Locati M, Bonecchi R, Corsi MM (2005) Chemokines and their receptors: roles in specific clinical conditions and measurement in the clinical laboratory. Am J Clin Pathol 123(Suppl): S82–S95

    PubMed  CAS  Google Scholar 

  47. Charo IF, Ransohoff RM (2006) The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 9;354(6):610–621

    Article  CAS  Google Scholar 

  48. Gerard C, Rollins BJ (2001) Chemokines and disease. Nat Immunol 2(2):108–115

    Article  PubMed  CAS  Google Scholar 

  49. DeFanis U, Wang G, Fedarko N et al (2007) CCR5+ T cells and frailty in older adults. J Am Geriatr Soc

    Google Scholar 

  50. Cesari M, Leeuwenburgh C, Lauretani F et al (2006) Frailty syndrome and skeletal muscle: results from the Invecchiare in Chianti study. Am J Clin Nutr 83(5):1142–1148

    PubMed  CAS  Google Scholar 

  51. Chaves PH, Semba RD, Leng SX et al (2005) Impact of anemia and cardiovascular disease on frailty status of community-dwelling older women: the Women’s Health and Aging Studies I and II. J Gerontol A Biol Sci Med Sci 60(6):729–735

    PubMed  Google Scholar 

  52. Newman AB, Gottdiener JS, Mcburnie MA et al (2001) Associations of subclinical cardiovascular disease with frailty. J Gerontol A Biol Sci Med Sci 56(3):M158–M166

    PubMed  CAS  Google Scholar 

  53. Cappola AR, Xue QL, Ferrucci L et al (2003) Insulin-like growth factor I and interleukin-6 contribute synergistically to disability and mortality in older women. J Clin Endocrinol Metab 88(5):2019–2025

    Article  PubMed  CAS  Google Scholar 

  54. Barzilay JI, Blaum C, Moore T et al (2007) Insulin resistance and inflammation as precursors of frailty: the Cardiovascular Health Study. Arch Intern Med 9;167(7):635–641

    Article  Google Scholar 

  55. Leng SX, Cappola AR, Andersen RE 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

    PubMed  CAS  Google Scholar 

  56. Fatkenheuer G, Pozniak AL, Johnson MA et al (2005) Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1. Nat Med 11(11):1170–1172

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Division of Geriatric Medicine and Gerontology and Center on Aging and Health, Johns Hopkins University School of Medicine, 5505 Hopkins Bayview Circle, Baltimore, Maryland, 21224, USA

    Sean X. Leng & Linda P. Fried

Authors
  1. Sean X. Leng
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  2. Linda P. Fried
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Editor information

Editors and Affiliations

  1. Research Center on Aging, Department of Medicine, Immunology Graduate Programme, Faculty of Medicine, University of Sherbrooke, 1036 Rue Belvedere, J1H 4C4, Sherbrooke, Quebec, Canada

    Tamas Fulop

  2. Department of Experimental Pathalogy, CIG Interdepartmental Center “L. Galvani” University of Bologna, Via San Giacomo 12, 40126, Bologna, Italy

    Claudio Franceschi

  3. Institute for Health and Life Sciences, 4-6-22 Kohinato, Bunkyo-ku, Tokyo, 112-0006, Japan

    Katsuiku Hirokawa

  4. ZMF - Zentrum Med. Forschung Abt. Transplant./ Immunologie, University of Tübingen, Waldhörnlestr. 22, 72072, Tübingen, Germany

    Graham Pawelec

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Leng, S.X., Fried, L.P. (2009). Inflammatory Markers and Frailty. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook on Immunosenescence. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9063-9_62

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