Journal of the American Medical Directors Association
ReviewProinflammatory Cytokines, Aging, and Age-Related Diseases
Section snippets
Immunosenescence
Immunosenescence is a progressive modification of the immune system that leads to greater susceptibility to infections, neoplasias, and autoimmune manifestations. This phenomenon is mainly due to prolonged antigenic stimulation across the life span.8 The main alteration responsible for immunosenescence concerns the functioning of T cells.9 Consequences of the thymic involution occurring with aging are decreases of the regulatory T lymphocytes and naïve T lymphocytes (in favor of memory T
Cytokines, Morbidity, and Mortality
Elevated levels of TNF-α, IL-6, and CRP are correlated with an increased risk of morbidity and mortality (all causes together), not only in a frail population (defined according to Fried et al's criteria38) but also in independent, nonfrail elderly.39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 The effects of cytokine dysregulation are independent of the other usual mortality risk factors (tobacco use, diabetes, arterial hypertension, hypercholesterolemia) and comorbid conditions.40, 42, 45, 46, 50
Cytokines and Frailty
Conclusion
Aging is accompanied by immune, hormonal, and adipose changes leading to a chronic inflammatory state. Levels of proinflammatory cytokines, principally TNF-α and IL-6, have damaging effects on aging (Table 1). They influence the onset of frailty, cognitive decline, and cardiological, neurological, and vascular events. They are also closely linked to the genesis of cancers, with cardiac remodeling in heart failure, and so forth. The limitations of this review arise from the numerous
Acknowledgments
The authors thank Dr Christian Michaud and Marie Josée Michaud (Sables d'Olonne, France).
References (151)
- et al.
Geriatric cachexia: The role of cytokines
Am J Clin Nutr
(1999) - et al.
Inflammation and Alzheimer's disease
Neurobiol Aging
(2000) - et al.
Marked increase with age of type 1 cytokines within memory and effector/cytotoxic CD8+ T cells in humans: A contribution to understand the relationship between inflammation and immunosenescence
Exp Gerontol
(2003) - et al.
Age-dependent modifications of Type 1 and Type 2 cytokines within virgin and memory CD4+ T cells in humans
Mech Ageing Dev
(2006) - et al.
Dysregulation between TH1 and TH2 T cell subpopulations in the elderly
Mech Ageing Dev
(1996) - et al.
Increase of plasma IL-6 concentration with age in healthy subjects
Life Sci
(1992) - et al.
Interleukin-6 and selected plasma proteins in healthy persons of different ages
Neurobiol Aging
(1994) - et al.
Plasma cytokine profiles in elderly humans
Mech Ageing Dev
(2003) - et al.
Lymphocyte proliferative response to PHA and anti-CD3/Ti monoclonal antibodies, T cell surface marker expression, and serum IL-2 receptor levels as biomarkers of age and health
Mech Ageing Dev
(1988) - et al.
Interleukin-2 production and activity in aged humans
Mech Ageing Dev
(1985)
Cytokine production and lymphocyte subpopulations in aged humans. An assessment during nocturnal sleep
Mech Ageing Dev
Postprandial endothelial activation in healthy subjects and in type 2 diabetic patients: Role of fat and carbohydrate meals
J Am Coll Cardiol
Elevated levels of tumor necrosis factor alpha and mortality in centenarians
Am J Med
Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly
Am J Med
Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: The Framingham Heart Study
Am J Med
Inflammation and stress-related candidate genes, plasma interleukin-6 levels, and longevity in older adults
Exp Gerontol
Enhanced generation of interleukins 1 beta and 6 may contribute to the cachexia of chronic disease
Am J Clin Nutr
Cytokine-cytokine interactions and the brain
Brain Res Bull
Differential expression of various cytokine receptors in the brain after stimulation with LPS in young and old mice
Exp Gerontol
Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes
Mech Ageing Dev
High innate production capacity of tumor necrosis factor-alpha and decline of handgrip strength in old age
Mech Ageing Dev
Increase in cytokine production (IL-1 beta, IL-6, TNF-alpha but not IFN-gamma, GM-CSF, or LIF) by stimulated whole blood cells in postmenopausal osteoporosis
Maturitas
The aging immune system: Primer and prospectus
Science
Inflammatory markers and physical performance in older persons: The InCHIANTI study
J Gerontol A Biol Sci Med Sci
The metabolic effects of tumor necrosis factor and other cytokines
Biotherapy
Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis
N Engl J Med
Inflammatory markers and onset of cardiovascular events: Results from the Health ABC study
Circulation
Immunosenescence of ageing
J Pathol
T cell senescence
Front Biosci
The aging of the immune system
Transpl Int
Inflamm-aging. An evolutionary perspective on immunosenescence
Ann N Y Acad Sci
Helper T-cell differentiation and plasticity: Insights from epigenetics
Immunology
Th1/Th2 changes in aging
Mech Ageing Dev
TH1 and TH2 cells: Different patterns of lymphokine secretion lead to different functional properties
Annu Rev Immunol
Chemokines, sTNF-Rs and sCD30 serum levels in healthy aged people and centenarians
Mech Ageing Dev
A shift to Th0 cytokine production by CD4+ cells in human longevity: Studies on two healthy centenarians
Eur J Immunol
Interleukin-6: A cytokine for gerontologists
J Am Geriatr Soc
Interleukin-6 and aging: Blood levels and mononuclear cell production increase with advancing age and in vitro production is modifiable by dietary restriction
Lymphokine Cytokine Res
The influence of age and gender on serum dehydroepiandrosterone sulphate (DHEA-S), IL-6, IL-6 soluble receptor (IL-6 sR) and transforming growth factor beta 1 (TGF-beta1) levels in normal healthy blood donors
Clin Exp Immunol
Serum dehydroepiandrosterone (DHEA) and DHEA sulfate are negatively correlated with serum interleukin-6 (IL-6), and DHEA inhibits IL-6 secretion from mononuclear cells in man in vitro: Possible link between endocrinosenescence and immunosenescence
J Clin Endocrinol Metab
A high plasma concentration of TNF-alpha is associated with dementia in centenarians
J Gerontol A Biol Sci Med Sci
Advancing age and insulin resistance: Role of plasma tumor necrosis factor-alpha
Am J Physiol
Signalling role of adipose tissue: Adipokines and inflammation in obesity
Biochem Soc Trans
Visceral and subcutaneous adipose tissue volumes are cross-sectionally related to markers of inflammation and oxidative stress: The Framingham Heart Study
Circulation
Estrogen, cytokines, and the control of osteoclast formation and bone resorption in vitro and in vivo
Osteoporos Int
A systematic review and meta-analyses on C-reactive protein in relation to periodontitis
J Clin Periodontol
Chronic stress and immunosenescence: A review
Neuroimmunomodulation
Frailty in older adults: Evidence for a phenotype
J Gerontol A Biol Sci Med Sci
Three-year change in inflammatory markers in elderly people and mortality: The Invecchiare in Chianti study
J Am Geriatr Soc
Serum IL-6 level and the development of disability in older persons
J Am Geriatr Soc
Cited by (763)
Interleukin-6 promotes visceral adipose tissue accumulation during aging via inhibiting fat lipolysis
2024, International ImmunopharmacologyAssociation of inflammatory markers with muscle and cognitive function in early and late-aging older adults
2024, Journal of Nutrition, Health and AgingIdentification of depression in patients with acute coronary syndrome using multiple serum biomarkers
2024, General Hospital PsychiatryRelation of the kynurenine pathway with normal age: A systematic review
2024, Mechanisms of Ageing and DevelopmentNavigating the nexus among thigh volume, myokine, and immunocytes in older adults with sarcopenia: A retrospective analysis in a male cohort
2024, Archives of Gerontology and Geriatrics
The authors declare no conflicts of interest.