Inflammatory mediators in the elderly

doi:10.1016/j.exger.2004.01.009

Experimental Gerontology

Volume 39, Issue 5, May 2004, Pages 687-699

https://doi.org/10.1016/j.exger.2004.01.009 Get rights and content

Abstract

Ageing is accompanied by 2–4-fold increases in plasma/serum levels of inflammatory mediators such as cytokines and acute phase proteins. A wide range of factors seems to contribute to this low-grade inflammation, including an increased amount of fat tissue, decreased production of sex steroids, smoking, subclinical infections (e.g. asymptomatic bacteriuria), and chronic disorders such as cardiovascular diseases and Alzheimer's disease. Furthermore, there is some evidence that ageing is associated with a dysregulated cytokine response following stimulation. Several inflammatory mediators such as tumour necrosis factor-α and interleukin-6 have the potential to induce/aggravate risk factors in age-associated pathology, providing a positive feedback mechanism. Thus, it is possible that inflammatory mediators constitute a link between life style factors, infections and physiological changes in the process of ageing on the one hand and risk factors for age-associated diseases on the other. Consistent with this, inflammatory mediators are strong predictors of mortality independently of other known risk factors and co-morbidity in elderly cohorts. A direct pathogenetic role of inflammatory mediators would be highly likely if longevity was shown to be associated with cytokine polymorphisms regulating cytokine production. Several studies support indeed this hypothesis but, unfortunately, findings in this area are conflicting, which probably reflects the complexity of the effect of cytokine polymorphisms and their interaction with the lifestyle and sex.

Section snippets

The ageing immune system

The term immunosenescence usually refers to the notion that there is an age-related dysfunction of the immune system. The number of studies in this area is large and, unfortunately, the results are often contradictory. Many investigators compare donors of different ages in cross-sectional studies and these populations differ in their genetic background, nutritional and environmental influences, co-morbidity, selection criteria, and in the techniques applied to measure immune parameters across

Ageing is associated with increased levels of circulating cytokines

Levels of circulating inflammatory mediators and their clinical importance have not been explored in population-based samples of elderly people until recently. Most studies have focused on interleukin (IL)-6, which has been called a cytokine for gerontologists (Ershler, 1993) and most studies report increased plasma/serum levels of this cytokine with advancing age (Wei et al., 1992, Ershler et al., 1993, Bruunsgaard et al., 1999a, Hager et al., 1994) although some studies have found no changes (

Cytokine production in vitro versus in vivo in elderly humans

A wide range of different factors is likely to contribute to increased low-grade inflammatory activity in elderly populations including decreased production of sex steroids, smoking, subclinical disorders such as atherosclerosis and asymptomatic bacteriuria, and a higher relative/absolute amount of fat tissue, which has been demonstrated to produce cytokines such as TNF-α and IL-6. Furthermore, increased levels of circulating inflammatory mediators may result from a constant, low-grade

Effects of inflammatory mediators in age-associated chronic diseases

The strong association between low-grade elevations in levels of circulating inflammatory mediators and high mortality risk independently of pre-existing morbidity, suggests that cytokines trigger/exaggerate pathological processes or act as very sensitive markers of subclinical disorders in elderly populations.

The longitudinal study of Danish centenarians has demonstrated that the extreme lifespan is accompanied by a high prevalence of CVD (>70%) and dementia (>50%) (Andersen-Ranberg et al.,

Concluding remarks

Ageing is associated with low-grade elevations in levels of circulating inflammatory mediators, which act as predictors of mortality independent of pre-existing morbidity. Moreover, there is strong evidence that the development of age-related multi-factorial conditions such as atherosclerosis, cognitive decline and the syndrome of frailty are associated to these elevations. The nature of these associations remains controversial, as it is unclear whether inflammatory mediators have primarily

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Mini–ReviewInflammatory mediators in the elderly

Abstract

Section snippets

The ageing immune system

Ageing is associated with increased levels of circulating cytokines

Cytokine production in vitro versus in vivo in elderly humans

Effects of inflammatory mediators in age-associated chronic diseases

Concluding remarks

Neurobiol. Aging

FEBS Lett.

Neurosci. Lett.

Mech. Ageing Dev.

Immunol. Allergy Clin. North Am.

Am. J. Med.

J. Nutr.

Cytokine

Exp. Gerontol.

Neurobiol. Aging

Am. J. Med.

Lancet

Neurosci. Lett.

J. Clin. Epidemiol.

J. Neuroimmunol.

Neurobiol. Aging

Lancet

Exp. Gerontol.

Am. Heart J.

Exp. Gerontol.

Mech. Ageing Dev.

Biol. Psychiatry

Brain Behav. Immunity

Mech. Ageing Dev.

Neurobiol. Aging

Brain Res. Bull.

Neurosci. Lett.

Blood levels of histamine, IL-1 beta, and TNF-alpha in patients with mild to moderate Alzheimer disease

Mol. Chem. Neuropathol.

Association between the TNFalpha-308 A/G polymorphism and the onset-age of Alzheimer disease

Am. J. Med. Genet.

Healthy centenarians do not exist, but autonomous centenarians do: a population-based study of morbidity among Danish centenarians

J. Am. Geriatr. Soc.

Impaired interleukin-1 signaling is associated with deficits in hippocampal memory processes and neural plasticity

Hippocampus

Lipoprotein(a) and lipoprotein profile in healthy centenarians: a reappraisal of vascular risk factors

FASEB J.

Quantitative and qualitative alterations of acute-phase proteins in healthy elderly persons

Age Ageing

Interleukin-6-174G>C polymorphism and risk of coronary heart disease in West of Scotland coronary prevention study (WOSCOPS)

Arterioscler. Thromb. Vasc. Biol.

Interleukin-6 production does not increase with age

J. Gerontol. A Biol. Sci. Med. Sci.

A gender-dependent genetic predisposition to produce high levels of IL-6 is detrimental for longevity

Eur. J. Immunol.

A high plasma concentration of TNF-alpha is associated with dementia in centenarians

J. Gerontol. A Biol. Sci. Med. Sci.

Impaired production of proinflammatory cytokines in response to lipopolysaccharide (LPS) stimulation in elderly humans

Clin. Exp. Immunol.

Elderly humans show prolonged in vivo inflammatory activity during pneumococcal infections

J. Infect. Dis.

Ageing, tumour necrosis factor-alpha (TNF-alpha) and atherosclerosis

Clin. Exp. Immunol.

The IL6-174G>C polymorphism is associated with cardiovascular diseases and mortality in 80-year-old humans

Exp. Gerontol.

Predicting death from tumour necrosis factor-alpha and interleukin-6 in 80-year-old people

Clin. Exp. Immunol.

The TNF-308G>A polymorphism is associated with dementia in the oldest old

Neurobiol. Aging

Muscle strength following resistance training is inversely correlated with baseline levels of soluble tumor necrosis Factor receptors in the oldest old

J. Am. Geriatr. Soc.

Zinc supplementation reconstitutes the production of interferon-alpha by leukocytes from elderly persons

J. Interferon Cytokine Res.

Effect of patient age on tests of the acute-phase response

Arch. Pathol. Lab. Med.

Cytokine antagonists in aged subjects and their relation with cellular immunity

J. Gerontol. A Biol. Sci. Med. Sci.

Age-dependent association between interleukin-1A (−889) genetic polymorphism and sporadic Alzheimer's disease. A meta-analysis

J. Neurol.

Association of an interleukin 1 alpha polymorphism with Alzheimer's disease

Neurology

Interleukin-6: a cytokine for gerontologists

Mini–Review
Inflammatory mediators in the elderly