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Aging, frailty and age-related diseases

Abstract

The concept of frailty as a medically distinct syndrome has evolved based on the clinical experience of geriatricians and is clinically well recognizable. Frailty is a nonspecific state of vulnerability, which reflects multisystem physiological change. These changes underlying frailty do not always achieve disease status, so some people, usually very elderly, are frail without a specific life threatening illness. Current thinking is that not only physical but also psychological, cognitive and social factors contribute to this syndrome and need to be taken into account in its definition and treatment. Together, these signs and symptoms seem to reflect a reduced functional reserve and consequent decrease in adaptation (resilience) to any sort of stressor and perhaps even in the absence of extrinsic stressors. The overall consequence is that frail elderly are at higher risk for accelerated physical and cognitive decline, disability and death. All these characteristics associated with frailty can easily be applied to the definition and characterization of the aging process per se and there is little consensus in the literature concerning the physiological/biological pathways associated with or determining frailty. It is probably true to say that a consensus view would implicate heightened chronic systemic inflammation as a major contributor to frailty. This review will focus on the relationship between aging, frailty and age-related diseases, and will highlight possible interventions to reduce the occurrence and effects of frailty in elderly people.

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References

  1. Abbatecola AM, Paolisso G (2008) Is there a relationship between insulin resistance and frailty syndrome? Curr Pharm Des 14(4):405–410

    CAS  PubMed  Article  Google Scholar 

  2. Angelopoulos P, Agouridaki H, Vaiopoulos H et al (2008) Cytokines in Alzheimer’s disease and vascular dementia. Int J Neurosci 118(12):1659–1672

    CAS  PubMed  Article  Google Scholar 

  3. Anker SD, von Haehling S (2004) Inflammatory mediators in chronic heart failure: an overview. Heart 90:464–470

    CAS  PubMed  Article  Google Scholar 

  4. 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 

  5. Bandeen-Roche K, Walston JD, Huang Y et al (2009) Measuring systemic inflammatory regulation in older adults: evidence and utility. Rejuvenation Res 12(6):403–410

    PubMed  Article  Google Scholar 

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

    PubMed  Article  Google Scholar 

  7. Beaufrère B, Morio B (2000) Fat and protein redistribution with aging: metabolic considerations. Eur J Clin Nutr 54:S48–S53

    PubMed  Google Scholar 

  8. Bergman H, Ferrucci L, Guralnik J et al (2007) Frailty: an emerging research and clinical paradigm—issues and controversies. J Gerontol A Biol Sci Med Sci 62(7):731–737

    PubMed  Google Scholar 

  9. Birks EJ, Felkin LE, Banner NR et al (2004) Increased toll-like receptor 4 in the myocardium of patients requiring left ventricular assist devices. J Heart Lung Transplant 23:228–235

    PubMed  Article  Google Scholar 

  10. Blaum CS, Xue QL, Tian J et al (2009) Is hyperglycemia associated with frailty status in older women? J Am Geriatr Soc 57(5):840–847

    PubMed  Article  Google Scholar 

  11. Bortz WM II (2002) A conceptual framework of frailty: a review. J Gerontol A Biol Sci Med Sci 57(5):M283–M288

    PubMed  Google Scholar 

  12. Boyle PA, Buchman AS, Wilson RS et al (2010) Physical frailty is associated with incident mild cognitive impairment in community-based older persons. J Am Geriatr Soc [Epub ahead of print]

  13. Buchman AS, Boyle PA, Wilson RS (2007) Frailty is associated with incident Alzheimer’s disease and cognitive decline in the elderly. Psychosom Med 69(5):483–489

    PubMed  Article  Google Scholar 

  14. Buchman AS, Schneider JA, Leurgans S, Bennett DA (2008) Physical frailty in older persons is associated with Alzheimer disease pathology. Neurology 71(7):499–504

    PubMed  Article  Google Scholar 

  15. Castle SC, Uyemura K, Rafi A et al (2005) Comorbidity is a better predictor of impaired immunity than chronological age in older adults. J Am Geriatr Soc 53:1565–1568

    PubMed  Article  Google Scholar 

  16. Castle SC, Uyemura K, Fulop T, Makinodan T (2007) Host resistance and immune responses in advanced age. Clin Geriatr Med 23:463–479

    PubMed  Article  Google Scholar 

  17. Cesari M, Penninx BW, Newman AB et al (2003) Inflammatory markers and onset of cardiovascular events: results from the Health ABC study. Circulation 108(19):2317–2322

    CAS  PubMed  Article  Google Scholar 

  18. Cesari M, Penninx BW, Pahor M et al (2004) Inflammatory markers and physical performance in older persons: the InCHIANTI study. J Gerontol A Biol Sci Med Sci 59(3):242–248

    PubMed  Google Scholar 

  19. Chang SS, Weiss CO, Xue QL, Fried LP (2009) Patterns of comorbid inflammatory diseases in frail older women: the Women’s Health and Aging Studies I and II. J Gerontol A Biol Sci Med Sci [Epub ahead of print]

  20. Chin A, Paw MJ, de Groot LC, van Gend SV et al (2003) Inactivity and weight loss: effective criteria to identify frailty. J Nutr Health Aging 7(1):55–60

    Google Scholar 

  21. Cook WL (2009) The intersection of geriatrics and chronic kidney disease: frailty and disability among older adults with kidney disease. Adv Chronic Kidney Dis 16(6):420–429

    PubMed  Article  Google Scholar 

  22. Daniels R, van Rossum E, de Witte L, Kempen GI, van den Heuvel W (2008) Interventions to prevent disability in frail community-dwelling elderly: a systematic review. BMC Health Serv Res 8:278

    PubMed  Article  Google Scholar 

  23. De Lepeleire J, Iliffe S, Mann E, Degryse JM et al (2009) Frailty: an emerging concept for general practice. Br J Gen Pract 59(562):e177–e182

    PubMed  Article  Google Scholar 

  24. de Souto Barreto P (2010) What is the role played by physical activity and exercise on the frailty syndrome? Perspectives for future research. Aging Clin Exp Res [Epub ahead of print]

  25. Derhovanessian E, Solana R, Larbi A, Pawelec G (2008) Immunity, aging and cancer. Immun Ageing 5:11

    PubMed  Article  CAS  Google Scholar 

  26. Derhovanessian E, Larbi A, Pawelec G (2009) Biomarkers of human immunosenescence: impact of Cytomegalovirus infection. Curr Opin Immunol 21(4):440–445

    CAS  PubMed  Article  Google Scholar 

  27. Després JP, Lemieux I, Bergeron J et al (2008) Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol 28:1039–1049

    PubMed  Article  CAS  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  30. Földes G, von Haehling S, Okonko DO et al (2008) Fluvastatin reduces increased blood monocyte Toll-like receptor 4 expression in whole blood from patients with chronic heart failure. Int J Cardiol 124:80–85

    PubMed  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

  32. Fried LP, Walston J (2003) Frailty and failure to thrive. In: Hazzard WR, Blass JP, Ettinger WH Jr, Halter JB, Ouslander J (eds) Principles of geriatric medicine and gerontology, 5th edn. McGraw-Hill, New York, pp 1487–1502

    Google Scholar 

  33. Fried LP, Tangen CM, Walston J et al (2001) Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 56(3):M146–M156

    CAS  PubMed  Google Scholar 

  34. Fried LP, Xue QL, Cappola AR et al (2009) Nonlinear multisystem physiological dysregulation associated with frailty in older women: implications for etiology and treatment. J Gerontol A Biol Sci Med Sci 64(10):1049–1057

    PubMed  Google Scholar 

  35. Fulop T, Larbi A, Wikby A et al (2005) Dysregulation of T-cell function in the elderly: scientific basis and clinical implications. Drugs Aging 22(7):589–603

    PubMed  Article  Google Scholar 

  36. Fulop T, Dupuis G, Fortin C et al (2006a) T cell response in aging: influence of cellular cholesterol modulation. Adv Exp Med Biol 584:157–169

    CAS  PubMed  Article  Google Scholar 

  37. Fulop T, Tessier D, Carpentier A (2006b) The metabolic syndrome. Pathol Biol (Paris) 54(7):375–386

    CAS  Google Scholar 

  38. Fulop T, Pawelec G, Castle S, Loeb M (2009) Immunosenescence and vaccination in nursing home patients. Clin Infect Dis 48(4):443–448

    PubMed  Article  Google Scholar 

  39. Fülöp T, Larbi A, Hirokawa K (2007) Immunosupportive therapies in aging. Clin Interv Aging 2(1):33–54

    PubMed  Article  Google Scholar 

  40. Gill TM, Gahbauer EA, Han L, Allore HG (2009) Trajectories of disability in the last year of life. New Engl J Med 362(13):1173–1180

    Article  Google Scholar 

  41. Goggins WB, Woo J, Sham A, Ho SC (2005) Frailty index as a measure of biological age in a Chinese population. J Gerontol A Biol Sci Med Sci 60(8):1046–1051

    PubMed  Google Scholar 

  42. Goulet ED, Hassaine A, Dionne IJ et al (2009) Frailty in the elderly is associated with insulin resistance of glucose metabolism in the postabsorptive state only in the presence of increased abdominal fat. Exp Gerontol 44(11):740–744

    CAS  PubMed  Article  Google Scholar 

  43. Gu D, Dupre ME, Sautter J (2009) Frailty and mortality among Chinese at advanced ages. J Gerontol B Psychol Sci Soc Sci 64(2):279–289

    PubMed  Google Scholar 

  44. Hackstaff L (2009) Factors associated with frailty in chronically ill older adults. Soc Work Health Care 48(8):798–811

    PubMed  Article  Google Scholar 

  45. Hazzard WR (2001) Depressed albumin and high-density lipoprotein cholesterol: signposts along the final common pathway of frailty. J Am Geriatr Soc 49(9):1253–1254

    CAS  PubMed  Article  Google Scholar 

  46. 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

    PubMed  Article  Google Scholar 

  47. Hubbard RE, Lang IA, Llewellyn DJ, Rockwood K (2010) Frailty, body mass index, and abdominal obesity in older people. J Gerontol A Biol Sci Med Sci 65:377–381

    PubMed  Google Scholar 

  48. Izaks GJ, Westendorp RG (2003) Ill or just old? Towards a conceptual framework of the relation between ageing and disease. BMC Geriatr 3:7

    PubMed  Article  Google Scholar 

  49. Jones D, Song X, Mitnitski A, Rockwood K (2005) Evaluation of a frailty index based on a comprehensive geriatric assessment in a population based study of elderly Canadians. Aging Clin Exp Res 17(6):465–471

    PubMed  Google Scholar 

  50. Kanapuru B, Ershler WB (2009) Inflammation, coagulation, and the pathway to frailty. Am J Med 122(7):605–613

    CAS  PubMed  Article  Google Scholar 

  51. Katagiri H, Ito Y, Ito S et al (2008) TNF-alpha induces thromboxane receptor signaling-dependent microcirculatory dysfunction in mouse liver. Shock 30(4):463–467

    CAS  PubMed  Article  Google Scholar 

  52. Kim JS, Wilson JM, Lee SR (2010) Dietary implications on mechanisms of sarcopenia: roles of protein, amino acids and antioxidants. J Nutr Biochem 21(1):1–13

    PubMed  Article  CAS  Google Scholar 

  53. Kirkwood TB (2005) Understanding the odd science of aging. Cell 120(4):437–447

    CAS  PubMed  Article  Google Scholar 

  54. Klein BE, Klein R, Knudtson MD, Lee KE (2005) Frailty, morbidity and survival. Arch Gerontol Geriatr 41(2):141–149

    PubMed  Article  Google Scholar 

  55. Kulminski AM, Arbeev KG, Ukraintseva SV (2008a) Changes in health status among participants of the Framingham Heart Study from the 1960s to the 1990s: application of an index of cumulative deficits. Ann Epidemiol 18:696–701

    PubMed  Article  Google Scholar 

  56. Kulminski AM, Culminskaya IV, Ukraintseva SV (2008b) Sex-specific health deterioration and mortality: the morbidity-mortality paradox over age and time. Exp Gerontol 43:1052–1057

    PubMed  Article  Google Scholar 

  57. Kulminski AM, Ukraintseva SV, Culminskaya IV (2008c) Cumulative deficits and physiological indices as predictors of mortality and long life. J Gerontol A Biol Sci Med Sci 63:1053–1059

    PubMed  Google Scholar 

  58. Kulminski AM, Ukraintseva SV, Kulminskaya IV (2008d) Cumulative deficits better characterize susceptibility to death in elderly people than phenotypic frailty: lessons from the Cardiovascular Health Study. J Am Geriatr Soc 56:898–903

    PubMed  Article  Google Scholar 

  59. Lages CS, Suffia I, Velilla PA et al (2008) Functional regulatory T cells accumulate in aged hosts and promote chronic infectious disease reactivation. J Immunol 181(3):1835–1848

    CAS  PubMed  Google Scholar 

  60. Landi F, Russo A, Pahor M et al (2008) Serum high-density lipoprotein cholesterol levels and mortality in frail, community-living elderly. Gerontology 54(2):71–78

    CAS  PubMed  Article  Google Scholar 

  61. Larbi A, Dupuis G, Khalil A et al (2006) Differential role of lipid rafts in the functions of CD4+ and CD8+ human T lymphocytes with aging. Cell Signal 18(7):1017–1030

    CAS  PubMed  Article  Google Scholar 

  62. Larbi A, Franceschi C, Mazzatti D et al (2008) Aging of the immune system as a prognostic factor for human longevity. Physiology (Bethesda) 23:64–74

    CAS  Google Scholar 

  63. Larbi A, Pawelec G, Witkowski JM et al (2009) Dramatic shifts in circulating CD4 but not CD8 T cell subsets in mild Alzheimer’s disease. J Alzheimer Dis 17(1):91–103

    CAS  Google Scholar 

  64. Leng SX, 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

    PubMed  Article  Google Scholar 

  65. Leng SX, Xue QL, Tian J (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

    PubMed  Article  Google Scholar 

  66. Libby P (2002) Inflammation in atherosclerosis. Nature 420:868–874

    CAS  PubMed  Article  Google Scholar 

  67. Lipsitz LA (2004) Physiological complexity, aging, and the path to frailty. Sci Aging Knowledge Environ 2004(16):pe16

  68. 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 

  69. Martin FC, Brighton P (2008) Frailty: different tools for different purposes? Age Ageing 37(2):129–131

    PubMed  Article  Google Scholar 

  70. Mitnitski AB, Mogilner AJ, Rockwood K (2001) Accumulation of deficits as a proxy measure of aging. ScientificWorldJournal 8(1):323–336

    Google Scholar 

  71. Mitnitski AB, Graham JE, Mogilner AJ, Rockwood K (2002) Frailty fitness and late-life mortality in relation to chronological and biological age. BMC Geriatr 2:1

    PubMed  Article  Google Scholar 

  72. Mitnitski A, Song X, Skoog I (2005) Relative fitness and frailty of elderly men and women in developed countries, in relation to mortality. J Am Geriatr Soc 53:2184–2189

    PubMed  Article  Google Scholar 

  73. Mori TA, Woodman RJ, Burke V et al (2003) Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers in treated-hypertensive type 2 diabetic subjects. Free Radic Biol Med 35:772–781

    CAS  PubMed  Article  Google Scholar 

  74. Morley JE (2009) Developing novel therapeutic approaches to frailty. Curr Pharm Des 15(29):3384–3395

    CAS  PubMed  Article  Google Scholar 

  75. Muszkat M, Friedman G, Dannenberg HD et al (2003) Response to influenza vaccination in community and in nursing home residing elderly: relation to clinical factors. Exp Gerontol 38:1199–1203

    PubMed  Article  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  77. Oxman MN (2007) Vaccination to prevent herpes zoster and postherpetic neuralgia. Hum Vaccin 3(2):64–68

    PubMed  Google Scholar 

  78. Pass RF, Zhang C, Evans A, Simpson T, Andrews W, Huang ML, Corey L, Hill J, Davis E, Flanigan C, Cloud G (2009) Vaccine prevention of maternal cytomegalovirus infection. N Engl J Med 360(12):1191–1199

    CAS  PubMed  Article  Google Scholar 

  79. Pawelec G, Derhovanessian E, Larbi A, Strindhall J, Wikby A (2009) Cytomegalovirus and human immunosenescence. Rev Med Virol 19(1):47–56

    CAS  PubMed  Article  Google Scholar 

  80. Pel-Littel RE, Schuurmans MJ, Emmelot-Vonk MH, Verhaar HJ (2009) Frailty: defining and measuring of a concept. J Nutr Health Aging 13(4):390–394

    CAS  PubMed  Article  Google Scholar 

  81. Pou KM, Massaro JM, Hoffmann U et al (2007) Visceral and subcutaneous adipose tissue volumes are cross-sectionally related to markers of inflammation and oxidative stress: the Framingham Heart Study. Circulation 116:1234–1241

    CAS  PubMed  Article  Google Scholar 

  82. Rafi A, Crawford W, Klaustermeyer W (2005) Declining cell-mediated immunity and increased chronic disease burden. Ann Allergy Asthma Immunol 94:445–450

    PubMed  Article  Google Scholar 

  83. Reiner AP, Aragaki AK, Gray SL (2009) Inflammation and thrombosis biomarkers and incident frailty in postmenopausal women. Am J Med 122(10):947–954

    CAS  PubMed  Article  Google Scholar 

  84. Richartz E, Stransky E, Batra A et al (2005) Decline of immune responsiveness: a pathogenetic factor in Alzheimer’s disease? J Psychiatr Res 39:535–543

    PubMed  Article  Google Scholar 

  85. Rockwood K (2005) What would make a definition of frailty successful? Age Ageing 34(5):432–434

    PubMed  Article  Google Scholar 

  86. Rockwood K, Mitnitski A (2007a) Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci 62(7):722–727

    PubMed  Google Scholar 

  87. Rockwood K, Mitnitski A (2007b) Geriatric syndromes. J Am Geriatr Soc 55:2092

    PubMed  Article  Google Scholar 

  88. Rockwood K, Fox RA, Stolee P (1994) Frailty in elderly people: an evolving concept. CMAJ 150:489–495

    CAS  PubMed  Google Scholar 

  89. Rockwood K, Stadnyk K, MacKnight C, McDowell I, Hébert R, Hogan DB (1999) A brief clinical measure of frailty. Lancet 353:205–206

    CAS  PubMed  Article  Google Scholar 

  90. Rockwood K, Hogan DB, MacKnight C (2000) Conceptualization and measurement of frailty in elderly people. Drugs Aging 17:295–302

    CAS  PubMed  Article  Google Scholar 

  91. Rockwood K, Howlett SE, MacKnight C et al (2004) Prevalence, attributes, and outcomes of fitness and frailty in community-dwelling older adults: report from the Canadian study of health and aging. J Gerontol A Biol Sci Med Sci 59(12):1310–1317

    PubMed  Google Scholar 

  92. Rockwood K, Mitnitski A, Song X et al (2006) Long-term risks of death and institutionalization of elderly people in relation to deficit accumulation at age 70. J Am Geriatr Soc 54(6):975–979

    PubMed  Article  Google Scholar 

  93. 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 62:738–743

    PubMed  Google Scholar 

  94. Rockwood K, Rockwood M, Mitnitksi A (2010) Physiological redundancy in older adults, in relation to the slope of a clinically derived Frailty Index. J Am Geriatr Soc 58:318–323

    PubMed  Article  Google Scholar 

  95. Rothman MD, Leo-Summers L, Gill TM (2008) Prognostic significance of potential frailty criteria. J Am Geriatr Soc 56(12):2211–2216

    PubMed  Article  Google Scholar 

  96. Roubenoff R, Harris TB (1997) Failure to thrive, sacropenia and functional decline in the elderly. Clin Geriatr Med 13(4):613–622

    CAS  PubMed  Google Scholar 

  97. Schalk BW, Visser M, Deeg DJ, Bouter LM (2004) Lower levels of serum albumin and total cholesterol and future decline in functional performance in older persons: the Longitudinal Aging Study Amsterdam. Age Ageing 33(3):266–272

    PubMed  Article  Google Scholar 

  98. Schuurmans H, Steverink N, Lindenberg S et al (2004) Old or frail: what tells us more? J Gerontol A Biol Sci Med Sci 59(9):M962–M965

    PubMed  Google Scholar 

  99. Searle SD, Mitnitski A, Gahbauer EA et al (2008) A standard procedure for creating a frailty index. BMC Geriatr 30(8):24

    Article  Google Scholar 

  100. Walston J, Arking DE, Fallin D et al (2005) IL-6 gene variation is not associated with increased serum levels of IL-6, muscle, weakness, or frailty in older women. Exp Gerontol 40(4):44–52

    Article  CAS  Google Scholar 

  101. 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

    PubMed  Article  Google Scholar 

  102. Wick G, Perschinka H, Millonig G (2001) Atherosclerosis as an autoimmune disease: an update. Trends Immunol 22:665–669

    CAS  PubMed  Article  Google Scholar 

  103. Wikby A, Månsson IA, Johansson B et al (2008) The immune risk profile is associated with age and gender: findings from three Swedish population studies of individuals 20–100 years of age. Biogerontology 9(5):299–308

    PubMed  Article  Google Scholar 

  104. Woo J, Tang NL, Suen E, Leung JC, Leung PC (2008) Telomeres and frailty. Mech Ageing Dev 129(11):642–648

    CAS  PubMed  Article  Google Scholar 

  105. 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

    PubMed  Article  Google Scholar 

  106. Yang Y, Lee LC (2010) Dynamics and heterogeneity in the process of human frailty and aging: evidence from the U.S. older adult population. J Gerontol B Psychol Sci Soc Sci 65B:246–255

    PubMed  Google Scholar 

  107. Yashin AI, Arbeev KG, Kulminski A (2008) What age trajectories of cumulative deficits and medical costs tell us about individual aging and mortality risk: findings from the NLTCS-Medicare data. Mech Ageing Dev 129:191–200

    PubMed  Article  Google Scholar 

  108. Yates FE (2002) Complexity of a human being: changes with age. Neurobiol Aging 23(1):17–19

    PubMed  Article  Google Scholar 

  109. Zoppini G, Verlato G, Targher G et al (2008) Variability of body weight, pulse pressure and glycaemia strongly predict total mortality in elderly type 2 diabetic patients: the Verona Diabetes Study. Diabetes Metab Res Rev 24(8):624–628

    PubMed  Article  Google Scholar 

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Acknowledgments

This work was partly supported by the Research Center on Aging, by the Canadian Initiative on Frailty and Aging, by a Canadian Institutes of Health Research (No 63149) grant and the University of Sherbrooke, and by EU-LSHG-CT-2007-036894 “LifeSpan” and DFG-PA 361/14-1 (to GP).

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Fulop, T., Larbi, A., Witkowski, J.M. et al. Aging, frailty and age-related diseases. Biogerontology 11, 547–563 (2010). https://doi.org/10.1007/s10522-010-9287-2

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Keywords

  • Frailty
  • Aging
  • Immunosenescence
  • Chronic diseases
  • Inflamm-aging
  • IRP