Ben Schöttker1, Kai-Uwe Saum2, Eugène H J M Jansen3, Paolo Boffetta4, Antonia Trichopoulou5, Bernd Holleczek6, Aida Karina Dieffenbach2, Hermann Brenner2. 1. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany. b.schoettker@dkfz-heidelberg.de. 2. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany. 3. Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, the Netherlands. 4. International Prevention Research Institute, Lyon, France. Institute for Translational Epidemiology and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York. 5. Hellenic Health Foundation, Athens, Greece. 6. Saarland Cancer Registry, Saarbrücken, Germany.
Abstract
BACKGROUND: The free radical/oxidative stress theory of aging has recently received much attention but the association of oxidative stress markers with all-cause mortality was not yet assessed in humans. METHODS: We measured derivatives of reactive oxygen metabolites (d-ROM) as a proxy for the reactive oxygen species concentration and total thiol levels (TTL) as a proxy for the redox control status in 2,932 participants of a population-based cohort study from Germany. RESULTS: The median age of the population was 70 years and 120 (4.1%) study participants died during a mean follow-up of 3.3 years. Compared with the bottom tertiles, the top tertiles of d-ROM and TTL concentrations were both associated with all-cause mortality in models adjusted for age, sex, education, smoking, physical activity, and alcohol consumption (hazard ratios and 95% confidence intervals: 1.63 [1.01; 2.63] and 0.68 [0.53; 0.87], respectively). Adding diseases, the inflammatory marker C-reactive protein or a cumulative somatic morbidity index did not alter the results for TTL. However, the association of d-ROM and mortality was attenuated and no longer statistically significant after adding C-reactive protein and the somatic morbidity index to the model. CONCLUSIONS: This study adds epidemiological evidence to the free radical/oxidative stress theory of aging. Both d-ROM and TTL were associated with mortality at older age. For TTL, this association was independent of baseline health status. Inflammation and higher general morbidity could be intermediate states on the pathway from high d-ROM levels to mortality. This hypothesis should to be explored by future studies with repeated measurements.
BACKGROUND: The free radical/oxidative stress theory of aging has recently received much attention but the association of oxidative stress markers with all-cause mortality was not yet assessed in humans. METHODS: We measured derivatives of reactive oxygen metabolites (d-ROM) as a proxy for the reactive oxygen species concentration and total thiol levels (TTL) as a proxy for the redox control status in 2,932 participants of a population-based cohort study from Germany. RESULTS: The median age of the population was 70 years and 120 (4.1%) study participants died during a mean follow-up of 3.3 years. Compared with the bottom tertiles, the top tertiles of d-ROM and TTL concentrations were both associated with all-cause mortality in models adjusted for age, sex, education, smoking, physical activity, and alcohol consumption (hazard ratios and 95% confidence intervals: 1.63 [1.01; 2.63] and 0.68 [0.53; 0.87], respectively). Adding diseases, the inflammatory marker C-reactive protein or a cumulative somatic morbidity index did not alter the results for TTL. However, the association of d-ROM and mortality was attenuated and no longer statistically significant after adding C-reactive protein and the somatic morbidity index to the model. CONCLUSIONS: This study adds epidemiological evidence to the free radical/oxidative stress theory of aging. Both d-ROM and TTL were associated with mortality at older age. For TTL, this association was independent of baseline health status. Inflammation and higher general morbidity could be intermediate states on the pathway from high d-ROM levels to mortality. This hypothesis should to be explored by future studies with repeated measurements.
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