Biomarkers of Oxidative and Mitochondrial Stress Are Associated With Accelerated Pace of Aging at Midlife in a Birth Cohort

Oxidative stress and mitochondrial dysfunction are proposed to play prominent roles in the biology of aging. Human studies are limited and confounded by metabolic disturbances associated with age-related diseases. In this study, we have measured biomarkers of oxidative and mitochondrial stress in blood samples from up to 864 participants in the longitudinal Dunedin Multidisciplinary Health and Development Study at age 45. We then determined the correlation between these cross-sectional biomarkers and the longitudinal Pace of Aging, a composite score that represents whole-organism functional decline in each participant from 26 to 45 years old, and facial age at 45 years old. Protein carbonyls and allantoin were selected as biomarkers for oxidative stress, and GDF-15 as a marker of mitochondrial stress. Midlife levels of these biomarkers were low but varied across the population. GDF-15 showed the strongest associations with the Pace of Aging (β = 0.26, p < .0001) and facial age (β = 0.12, p = .001) in sex- and smoking-adjusted models. The Pace of Aging was also significantly associated with allantoin (β = 0.14, p < .0001) and protein carbonyls (β = 0.09, p = .005), and allantoin was associated with facial age (β = 0.08, p = .02). These associations remained when the limited number of participants with age-related disease were removed from the analyses. Our results provide evidence of increased oxidative stress and mitochondrial stress in faster-aging humans at midlife, well before the onset of age-related disease.