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Biomarkers of oxidative and mitochondrial stress are associated with accelerated pace of aging at midlife in a birth cohort | 2025
King-Hudson, Te-Rina J Pearson, Andree G Dunstan-Harrison, Caitlin Powell, Mathew T Magon,
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The Journals of Gerontology: Series A, 2025, .
10.1093/gerona/glaf105
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Our ref: RO821
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. Mid-life 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 < 0.0001) and facial age (β = 0.12, p =0.001) in sex and smoking adjusted models. The Pace of Aging was also significantly associated with allantoin (β = 0.14, p < 0.0001) and protein carbonyls (β = 0.09, p = 0.005), and allantoin was also associated with facial age (β = 0.08, p = 0.02). 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.
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Adult Physical Function Has Roots in Early Childhood Brain Function: A Five-Decade Cohort Study | 2024
Xie, J. K.; Caspi, A.; Harrington, H.; Houts, R.; Pietrosimone,
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In press. The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences, 2024, 79(9), .
10.1093/geronb/gbae119
Our ref: RO821
OBJECTIVES: Tests of physical function are often thought to measure functioning that is (1) musculoskeletal, and (2) newly declining in adult life. In contrast, this study aimed to: (1) add to evidence that physical-function tests also measure brain function, and (2) test the novel hypothesis that adult physical function is associated with brain function beginning in early childhood. We investigated early childhood brain function and midlife physical function in the Dunedin Study, a 5-decade longitudinal birth cohort (n = 1,037). METHODS: Brain function was measured at age 3 using 5 measures which formed a reliable composite (neurological examination, cognitive and motor tests, and temperament ratings). Physical function was measured at age 45 using 5 measures which formed a reliable composite (gait speed, step-in-place, chair stands, balance, and grip strength). RESULTS: Children with worse age-3 brain function had worse midlife physical function as measured by the age-45 composite, even after controlling for childhood socioeconomic status (β: 0.23; 95% CI: 0.16 to 0.30; p < .001). Worse age-3 brain function significantly predicted slower gait speed, fewer steps-in-place and chair-stands, worse balance, and weaker grip strength. DISCUSSION: Children with poorer brain function were more likely to have poorer physical-function scores as adults. In addition to indicating recent musculoskeletal decline, physical-function tests may also provide indications of lifelong, integrated brain-body health. By reconceptualizing the meaning of physical-function scores, clinicians can orient the use of physical-function tests in a more holistic approach to health care.
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