Biology subjects

Crimmins, E.

Publications and source records attributed to Crimmins, E..

3 recordsLinked to original sources

bioRxiv2026

Stressful exposure from the 2004 Indian Ocean Tsunami drives long-term changes in thyroid hormone physiology

Stressful events are associated with long-term adverse health impacts, but the causal mechanisms linking these exposures to subsequent disease remain poorly understood. One plausible mechanism is persistent changes to hormonal signaling that regulate metabolic homeostasis. Here, we examine the long-term impacts of stress associated with exposure to the 2004 Indian Ocean tsunami on levels of free triiodothyronine (FT3), a circulating measure of biologically active thyroid hormone, using data from the Study of Tsunami Aftermath and Recovery. We measure biomarkers 20 years after the tsunami in a population-representative sample age 35y+ in 2024 who, at the time of the tsunami, were living along the coast of Aceh, Indonesia, the most affected part of the Indian Ocean Basin. Because respondents were first interviewed before the tsunami and subsequently tracked regardless of migration, the sample avoids a major source of selection bias common in long-term disaster studies. We identify the causal effect of tsunami exposure using variation in community-level tsunami mortality, comparing communities within the same sub-district. We find that greater tsunami exposure reduced levels of FT3 20 years later. Exposure also altered relationships between FT3, body composition, and cortisol and increased cardiometabolic risk. These findings identify persistent alteration of thyroid hormone physiology as a potential pathway linking severe stressful exposures to long-term cardiometabolic disease risk.

physiology↗

bioRxiv2021

Genetic variation in ALDH4A1 predicts muscle health over the lifespan and across species

Environmental stress can negatively impact organismal aging, however, the long-term impact of endogenously derived reactive oxygen species from normal cellular metabolism remains less clear. Here we define the evolutionarily conserved mitochondrial enzyme ALH-6/ALDH4A1 as a biomarker for age-related changes in muscle health by combining C. elegans genetics and a gene-wide association study (GeneWAS) from aged human participants of the US Health and Retirement Study (HRS)1-4. In a screen for mutations that activate SKN-1-dependent oxidative stress responses in the muscle of C. elegans5-7, we identified 96 independent genetic mutants harboring loss-of-function alleles of alh-6, exclusively. These genetic mutations map across the ALH-6 polypeptide, which lead to age-dependent loss of muscle health. Intriguingly, genetic variants in ALDH4A1 differentially impact age-related muscle function in humans. Taken together, our work uncovers mitochondrial alh-6/ALDH4A1 as a critical component of normal muscle aging across species and a predictive biomarker for muscle health over the lifespan.

genetics↗

bioRxiv2018

Phenotypic Age: a novel signature of mortality and morbidity risk

BackgroundA persons rate of aging has important implications for his/her risk of death and disease, thus, quantifying aging using observable characteristics has important applications for clinical, basic, and observational research. We aimed to validate a novel aging measure, \"Phenotypic Age\", constructed based on routine clinical chemistry measures, by assessing its applicability for differentiating risk for morbidity and mortality in both healthy and unhealthy populations of various ages.\n\nMethodsA nationally representative US sample, NHANES III, was used to derive \"Phenotypic Age\" based on a linear combination of chronological age and nine multi-system clinical chemistry measures, selected via cox proportional elastic net. Mortality predictions were validated using an independent sample (NHANES IV), consisting of 11,432 participants, for whom we observed a total of 871 deaths, ascertained over 12.6 year of follow-up. Proportional hazard models and ROC curves were used to evaluate predictions.\n\nResultsPhenotypic Age was significantly associated with all-cause mortality and cause-specific mortality. These results were robust to age and sex stratification, and remained even when excluding short-term mortality. Similarly, Phenotypic Age was associated with mortality among seemingly \"healthy\" participants--defined as those who were disease-free and had normal BMI at baseline--as well as the oldest-old (aged 85+)--a group with high disease burden.\n\nConclusionsPhenotypic Age is a reliable predictor of all-cause and cause-specific mortality in multiple subgroups of the population. Risk stratification by this composite measure is far superior to that of the individual measures that go into it, as well as traditional measures of health. It is able to differentiate individuals who appear healthy, who may have otherwise been missed using traditional health assessments. Further, it can differentiate risk among persons with shared disease burden. Overall, this easily measured metric may be useful in the clinical setting and facilitate secondary and tertiary prevention strategies.

epidemiology↗