title: Chronic inflammation as a determinant of future aging phenotypes.
abstract: BACKGROUND
  The importance of chronic inflammation as a determinant of aging phenotypes may have been underestimated in previous studies that used a single measurement of inflammatory markers. We assessed inflammatory markers twice over a 5-year exposure period to examine the association between chronic inflammation and future aging phenotypes in a large population of men and women.
  
  
  METHODS
  We obtained data for 3044 middle-aged adults (28.2% women) who were participating in the Whitehall II study and had no history of stroke, myocardial infarction or cancer at our study's baseline (1997-1999). Interleukin-6 was measured at baseline and 5 years earlier. Cause-specific mortality, chronic disease and functioning were ascertained from hospital data, register linkage and clinical examinations. We used these data to create 4 aging phenotypes at the 10-year follow-up (2007-2009): successful aging (free of major chronic disease and with optimal physical, mental and cognitive functioning), incident fatal or nonfatal cardiovascular disease, death from noncardiovascular causes and normal aging (all other participants).
  
  
  RESULTS
  Of the 3044 participants, 721 (23.7%) met the criteria for successful aging at the 10-year follow-up, 321 (10.6%) had cardiovascular disease events, 147 (4.8%) died from noncardiovascular causes, and the remaining 1855 (60.9%) were included in the normal aging phenotype. After adjustment for potential confounders, having a high interleukin-6 level (> 2.0 ng/L) twice over the 5-year exposure period nearly halved the odds of successful aging at the 10-year follow-up (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.38-0.74) and increased the risk of future cardiovascular events (OR 1.64, 95% CI 1.15-2.33) and noncardiovascular death (OR 2.43, 95% CI 1.58-3.80).
  
  
  CONCLUSIONS
  Chronic inflammation, as ascertained by repeat measurements, was associated with a range of unhealthy aging phenotypes and a decreased likelihood of successful aging. Our results suggest that assessing long-term chronic inflammation by repeat measurement of interleukin-6 has the potential to guide clinical practice.
authors.forename: Tasnime N
authors.initials: TN
authors.lastname: Akbaraly
authors.forename: Mark
authors.initials: M
authors.lastname: Hamer
authors.forename: Jane E
authors.initials: JE
authors.lastname: Ferrie
authors.forename: Gordon
authors.initials: G
authors.lastname: Lowe
authors.forename: G David
authors.initials: GD
authors.lastname: Batty
authors.forename: Gareth
authors.initials: G
authors.lastname: Hagger-Johnson
authors.forename: Archana
authors.initials: A
authors.lastname: Singh-Manoux
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Shipley
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimäki
mesh_terms: D000375:Aging / Q000276:immunology*; D002318:Cardiovascular Diseases / Q000276:immunology*; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6
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