title: Evidence for the free radical/oxidative stress theory of ageing from the CHANCES consortium: a meta-analysis of individual participant data.
abstract: BACKGROUND
  The free radical/oxidative stress theory of ageing has received considerable attention, but the evidence on the association of oxidative stress markers with mortality is sparse.
  
  
  METHODS
  We measured derivatives of reactive oxygen metabolite (D-ROM) levels as a proxy for the reactive oxygen species concentration and total thiol levels (TTL) as a proxy for the redox control status in 10,622 men and women (age range, 45-85 years), from population-based cohorts from Germany, Poland, Czech Republic, and Lithuania, of whom 1,702 died during follow-up.
  
  
  RESULTS
  Both oxidative stress markers were significantly associated with all-cause mortality independently from established risk factors (including inflammation) and from each other in all cohorts. Regarding cause-specific mortality, compared to low D-ROM levels (≤ 340 Carr U), very high D-ROM levels (>500 Carr U) were strongly associated with both cardiovascular (relative risk (RR), 5.09; 95 % CI, 2.67-9.69) and cancer mortality (RR, 4.34; 95 % CI, 2.31-8.16). TTL was only associated with CVD mortality (RR, 1.30; 95 % CI, 1.15-1.48, for one-standard-deviation-decrease). The strength of the association of TTL with CVD mortality increased with age of the participants (RR for one-standard-deviation-decrease in those aged 70-85 years was 1.65; 95 % CI, 1.22-2.24).
  
  
  CONCLUSIONS
  In these four population-based cohort studies from Central and Eastern Europe, the oxidative stress serum markers D-ROM and TTL were independently and strongly associated with all-cause and CVD mortality. In addition, D-ROM levels were also strongly associated with cancer mortality. This study provides epidemiological evidence supporting the free radical/oxidative stress theory of ageing and suggests that d-ROMs and TTL are useful oxidative stress markers associated with premature mortality.
authors.affiliation: Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. b.schoettker@dkfz.de.|Network Aging Research, University of Heidelberg, Bergheimer Strasse 20, 69120, Heidelberg, Germany. b.schoettker@dkfz.de.
authors.forename: Ben
authors.initials: B
authors.lastname: Schöttker
authors.affiliation: Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.|Network Aging Research, University of Heidelberg, Bergheimer Strasse 20, 69120, Heidelberg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
authors.affiliation: Laboratory for Health Protection Research, National Institute for Public Health and the Environment, PO Box 1, 3720, BA, Bilthoven, The Netherlands.
authors.forename: Eugène H J M
authors.initials: EH
authors.lastname: Jansen
authors.affiliation: Department Epidemiology and Public Health, University College London, 1-19 Torrington Place, London, WC1E 6BT, Great Britain.
authors.forename: Julian
authors.initials: J
authors.lastname: Gardiner
authors.affiliation: Department Epidemiology and Public Health, University College London, 1-19 Torrington Place, London, WC1E 6BT, Great Britain.
authors.forename: Anne
authors.initials: A
authors.lastname: Peasey
authors.affiliation: National Institute of Public Health, Prague, Czech Republic.
authors.forename: Růžena
authors.initials: R
authors.lastname: Kubínová
authors.affiliation: Jagiellonian University Medical College, Faculty of Health Sciences, Krakow, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pająk
authors.affiliation: Jagiellonian University Medical College, Faculty of Health Sciences, Krakow, Poland.
authors.forename: Roman
authors.initials: R
authors.lastname: Topor-Madry
authors.affiliation: Institute of Cardiology of Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Abdonas
authors.initials: A
authors.lastname: Tamosiunas
authors.affiliation: Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
authors.forename: Kai-Uwe
authors.initials: KU
authors.lastname: Saum
authors.affiliation: Saarland Cancer Registry, Präsident Baltz-Strasse 5, 66119, Saarbrücken, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Holleczek
authors.affiliation: Department Epidemiology and Public Health, University College London, 1-19 Torrington Place, London, WC1E 6BT, Great Britain.
authors.forename: Hynek
authors.initials: H
authors.lastname: Pikhart
authors.affiliation: Department Epidemiology and Public Health, University College London, 1-19 Torrington Place, London, WC1E 6BT, Great Britain.
authors.forename: Martin
authors.initials: M
authors.lastname: Bobak
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology*; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood / Q000401:mortality; D005061:Europe, Eastern; D005260:Female; D005609:Free Radicals / Q000097:blood*; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000097:blood*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D005609:Free Radicals; D017382:Reactive Oxygen Species