Browsing by Author "Shalev, Idan"

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    Change in the Rate of Biological Aging in Response to Caloric Restriction: CALERIE Biobank Analysis.
    (J Gerontol A Biol Sci Med Sci, 2017-05-22) Belsky, Daniel W; Huffman, Kim M; Pieper, Carl F; Shalev, Idan; Kraus, William E
    Biological aging measures have been proposed as proxies for extension of healthy lifespan in trials of geroprotective therapies that aim to slow aging. Several methods to measure biological aging show promise; but it is not known if these methods are sensitive to changes caused by geroprotective therapy. We conducted analysis of two proposed methods to quantify biological aging using data from a recently concluded trial of an established geroprotector, caloric restriction. We obtained data from the National Institute on Aging CALERIE randomized trial through its public-access biobank (https://calerie.duke.edu/). The CALERIE trial randomized N=220 non-obese adults to 25% caloric restriction (n=145; 11.7% caloric restriction was achieved, on average) or to maintain current diet (n=75) for two years. We analyzed biomarker data collected at baseline, 12-, and 24-month follow-up assessments. We applied published biomarker algorithms to these data to calculate two biological age measures, Klemera-Doubal Method Biological Age and homeostatic dysregulation. Intent-to-treat analysis using mixed-effects growth models of within-person change over time tested if caloric restriction slowed increase in measures of biological aging across follow-up. Analyses of both measures indicated caloric restriction slowed biological aging. Weight loss did not account for the observed effects. Results suggest future directions for testing of geroprotective therapies in humans.
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    Is chronic asthma associated with shorter leukocyte telomere length at midlife?
    (Am J Respir Crit Care Med, 2014-08-15) Belsky, Daniel W; Shalev, Idan; Sears, Malcolm R; Hancox, Robert J; Lee Harrington, Hona; Houts, Renate; Moffitt, Terrie E; Sugden, Karen; Williams, Benjamin; Poulton, Richie; Caspi, Avshalom
    RATIONALE: Asthma is prospectively associated with age-related chronic diseases and mortality, suggesting the hypothesis that asthma may relate to a general, multisystem phenotype of accelerated aging. OBJECTIVES: To test whether chronic asthma is associated with a proposed biomarker of accelerated aging, leukocyte telomere length. METHODS: Asthma was ascertained prospectively in the Dunedin Multidisciplinary Health and Development Study cohort (n = 1,037) at nine in-person assessments spanning ages 9-38 years. Leukocyte telomere length was measured at ages 26 and 38 years. Asthma was classified as life-course-persistent, childhood-onset not meeting criteria for persistence, and adolescent/adult-onset. We tested associations between asthma and leukocyte telomere length using regression models. We tested for confounding of asthma-leukocyte telomere length associations using covariate adjustment. We tested serum C-reactive protein and white blood cell counts as potential mediators of asthma-leukocyte telomere length associations. MEASUREMENTS AND MAIN RESULTS: Study members with life-course-persistent asthma had shorter leukocyte telomere length as compared with sex- and age-matched peers with no reported asthma. In contrast, leukocyte telomere length in study members with childhood-onset and adolescent/adult-onset asthma was not different from leukocyte telomere length in peers with no reported asthma. Adjustment for life histories of obesity and smoking did not change results. Study members with life-course-persistent asthma had elevated blood eosinophil counts. Blood eosinophil count mediated 29% of the life-course-persistent asthma-leukocyte telomere length association. CONCLUSIONS: Life-course-persistent asthma is related to a proposed biomarker of accelerated aging, possibly via systemic eosinophilic inflammation. Life histories of asthma can inform studies of aging.
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    Stress biomarkers and child development in young children in Bangladesh.
    (Psychoneuroendocrinology, 2024-03) Butzin-Dozier, Zachary; Mertens, Andrew N; Tan, Sophia T; Granger, Douglas A; Pitchik, Helen O; Il'yasova, Dora; Tofail, Fahmida; Rahman, Md Ziaur; Spasojevic, Ivan; Shalev, Idan; Ali, Shahjahan; Karim, Mohammed Rabiul; Shahriar, Sunny; Famida, Syeda Luthfa; Shuman, Gabrielle; Shoab, Abul K; Akther, Salma; Hossen, Md Saheen; Mutsuddi, Palash; Rahman, Mahbubur; Unicomb, Leanne; Das, Kishor K; Yan, Liying; Meyer, Ann; Stewart, Christine P; Hubbard, Alan E; Naved, Ruchira Tabassum; Parvin, Kausar; Mamun, Md Mahfuz Al; Luby, Stephen P; Colford, John M; Fernald, Lia CH; Lin, Audrie

    Background

    Hundreds of millions of children in low- and middle-income countries are exposed to chronic stressors, such as poverty, poor sanitation and hygiene, and sub-optimal nutrition. These stressors can have physiological consequences for children and may ultimately have detrimental effects on child development. This study explores associations between biological measures of chronic stress in early life and developmental outcomes in a large cohort of young children living in rural Bangladesh.

    Methods

    We assessed physiologic measures of stress in the first two years of life using measures of the hypothalamic-pituitary-adrenal (HPA) axis (salivary cortisol and glucocorticoid receptor gene methylation), the sympathetic-adrenal-medullary (SAM) system (salivary alpha-amylase, heart rate, and blood pressure), and oxidative status (F2-isoprostanes). We assessed child development in the first two years of life with the MacArthur-Bates Communicative Development Inventories (CDI), the WHO gross motor milestones, and the Extended Ages and Stages Questionnaire (EASQ). We compared development outcomes of children at the 75th and 25th percentiles of stress biomarker distributions while adjusting for potential confounders using generalized additive models, which are statistical models where the outcome is predicted by a potentially non-linear function of predictor variables.

    Results

    We analyzed data from 684 children (49% female) at both 14 and 28 months of age; we included an additional 765 children at 28 months of age. We detected a significant relationship between HPA axis activity and child development, where increased HPA axis activity was associated with poor development outcomes. Specifically, we found that cortisol reactivity (coefficient -0.15, 95% CI (-0.29, -0.01)) and post-stressor levels (coefficient -0.12, 95% CI (-0.24, -0.01)) were associated with CDI comprehension score, post-stressor cortisol was associated with combined EASQ score (coefficient -0.22, 95% CI (-0.41, -0.04), and overall glucocorticoid receptor methylation was associated with CDI expression score (coefficient -0.09, 95% CI (-0.17, -0.01)). We did not detect a significant relationship between SAM activity or oxidative status and child development.

    Conclusions

    Our observations reveal associations between the physiological evidence of stress in the HPA axis with developmental status in early childhood. These findings add to the existing evidence exploring the developmental consequences of early life stress.