Schöttker, Ben; Brenner, Hermann; Jansen, Eugène HJM; Gardiner, Julian; Peasey, Anne; Kubínová, Růžena; Pajak, Andrzej; ... Bobak, Martin; + view all Schöttker, Ben; Brenner, Hermann; Jansen, Eugène HJM; Gardiner, Julian; Peasey, Anne; Kubínová, Růžena; Pajak, Andrzej; Topor-Madry, Roman; Tamosiunas, Abdonas; Saum, Kai-Uwe; Holleczek, Bernd; Pikhart, Hynek; Bobak, Martin; - view fewer (2015) Evidence for the free radical/oxidative stress theory of ageing from the CHANCES consortium: a meta-analysis of individual participant data. BMC Medicine , 13 , Article 300. 10.1186/s12916-015-0537-7.

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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.

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