Dayoon Kwon

All Publications

• Pregnancy and breastfeeding are associated with less later-life cognitive decline in a longitudinal, prospective cohort. Alzheimer's & dementia : the journal of the Alzheimer's Association Fox, M. M., Bramen, J. E., Kwon, D., Espeland, M. A., Sun, Y., Zhang, L., Shadyab, A. H., Casanova, R., Manson, J. E., Chang, M. Y., Porter, V. R., Farland, L. V., Xiao, Q., Wild, R. A., Siddarth, P., Crandall, C. J. 2026; 22 (1): e71072

  Abstract

  The brains of female mammals evolved to undergo structural and functional changes during pregnancy and lactation, equipping them for motherhood. However, long-term cognitive health implications of these adaptations in women are poorly understood.In the Women's Health Initiative (WHI) Memory Study (WHIMS; n = 7427) and WHI Study of Cognitive Aging (WHISCA; n = 2304), postmenopausal women completed reproductive history interviews, annual global cognitive assessment from mean age 70 for up to 13 years, and multi-domain cognitive testing for up to 8 years.Each additional month pregnant was associated with higher scores of global cognition. Each additional month of breastfeeding corresponded to higher scores of global cognition, verbal memory, and visual memory. We observed equivalent results for binary formulations of gravidity and breastfeeding.Low rates of fertility and breastfeeding may have implications for postmenopausal cognitive health at the population level. Next steps include examining mechanisms linking women's reproductive history with postmenopausal cognitive health.Motherhood may leave an enduring mark on women's brains, shaping cognitive health. Over 7000 women were assessed annually from approximately age 70 for up to 13 years. Ever being pregnant and cumulative time pregnant were linked with better cognition. Ever having breastfed and more time breastfeeding were linked with better cognition. These results imply that declining fertility may affect cognitive aging in future generations.

  View details for DOI 10.1002/alz.71072

  View details for PubMedID 41499366

  View details for PubMedCentralID PMC12778429

• A unified framework for systematic curation and evaluation of aging biomarkers. Nature aging Ying, K., Paulson, S., Eames, A., Tyshkovskiy, A., Li, S., Eynon, N., Jacques, M., Grolaux, R., Seale, K., Jacques, E., Goeminne, L. J., Cipriano, A., Perez-Guevara, M., Emamifar, M., Casas Martínez, M., Kwon, D., Kosheleva, A., Snyder, M., Gobel, D., Herzog, C., McCartney, D. L., Marioni, R. E., Lasky-Su, J., Poganik, J. R., Moqri, M., Gladyshev, V. N. 2025

  Abstract

  Aging biomarkers are essential tools for quantifying biological aging, but systematic validation has been hindered by methodological inconsistencies and fragmented datasets. Here we show that the ability of traditional aging clocks to predict chronological age does not correlate with mortality prediction capacity (R = 0.12, P = 0.67), suggesting that these metrics capture distinct biological processes. We developed Biolearn, an open-source framework enabling standardized evaluation of 39 biomarkers across over 20,000 individuals from diverse cohorts. The Horvath skin and blood clock achieved the highest chronological age accuracy (R2 = 0.88), while GrimAge2 demonstrated the strongest mortality association (hazard ratio = 2.57) and healthspan prediction (hazard ratio = 2.00). Our systematic evaluation reveals considerable heterogeneity in biomarker performance across different clinical outcomes, with optimal biomarkers varying according to specific application. Biolearn provides unified data processing pipelines with quality control and cell-type deconvolution capabilities, establishing a foundation for reproducible aging research and facilitating development of robust aging biomarkers.

  View details for DOI 10.1038/s43587-025-00987-y

  View details for PubMedID 41188602

  View details for PubMedCentralID 11088934

• Of scents and cytokines: How olfactory and food aversions relate to nausea and immunomodulation in early pregnancy. Evolution, medicine, and public health Kwon, D., Fessler, D. M., Knorr, D. A., Wiley, K. S., Sartori, J., Coall, D. A., Fox, M. M. 2025; 13 (1): 269-280

  Abstract

  During pregnancy, the maternal body undergoes extensive physiological adaptations to support embryonic growth, including whole-body remodeling, that may induce odor and food aversions, as well as nausea and vomiting. The biological mechanisms behind odor and food aversions, as well as nausea and vomiting in early pregnancy, remain largely unexplored. Our study investigated associations between these changes and cytokine profiles during pregnancy.A cohort of pregnant Latina women in Southern California (n = 58) completed a structured questionnaire on pregnancy "morning sickness"-related symptoms and aversions. Maternal plasma cytokine levels were measured between 5 and 17 weeks' gestation.About 64% of participants experienced odor or food aversions, primarily to tobacco smoke and meat; 67% reported nausea, and 66% experienced vomiting. Multivariable linear regression models revealed that odor aversions were associated with increased pro-inflammatory T-helper-cell type (Th) 1 composite cytokine levels. Women who found tobacco smoke aversive exhibited a shift toward Th1 immune responses, indicated by a higher Th1:Th2 ratio. Food aversions also showed a positive association with Th1 cytokine levels. A borderline positive association was noted between nausea and vomiting and the Th1:Th2 ratio.These findings are consistent with the hypothesis that gestational changes in olfactory and gustatory experience, and nausea and vomiting, reflect adaptive upregulation of behavioral prophylaxis in ways that could protect the fetus. If this elevated Th1:Th2 ratio and pro-inflammatory phenotype are part of the maternal and embryonic response to embryogenesis, the behavioral and biological markers that we explore may provide an accessible index of fetal development during early pregnancy.

  View details for DOI 10.1093/emph/eoaf016

  View details for PubMedID 41017872

  View details for PubMedCentralID PMC12476167

• Challenges in studying air pollution to neurodegenerative diseases. Environmental research Kwon, D., Paul, K. C., O'Sharkey, K., Paik, S. A., Yu, Y., Bronstein, J. M., Ritz, B. 2025; 278: 121597

  Abstract

  Exposure to ambient air pollution is ubiquitous and unavoidable. While associations between air pollution and cardiometabolic diseases are well-established, its role in neurodegenerative diseases, such as Alzheimer's disease and related dementias (ADRD) and Parkinson's disease (PD), has only recently begun to emerge. This narrative review provides an overview of current findings and discusses challenges and opportunities for future epidemiologic research. Mechanistically, air pollution may contribute to ADRD and PD through neuroinflammation, oxidative stress, and cerebrovascular damage. Long-term exposure to high levels of air pollution may increase the risk of ADRD and PD. Over the past 20 years, more than 50 studies have examined air pollution and ADRD, while fewer studies have focused on PD. Although the estimated effects are modest in size, they translate into a substantial number of affected individuals due to the widespread nature of the exposure and an increasingly aging population worldwide. Future research should extend exposure periods to cover younger and middle ages, estimate the effects of long-term cumulative exposures, and evaluate moderators and mediators, such as diet, physical activity, green space, and noise. More studies are also needed to include large and diverse populations, including those with special vulnerabilities and emerging exposures like wildfire smoke.

  View details for DOI 10.1016/j.envres.2025.121597

  View details for PubMedID 40220887

• Interaction Between Traffic-Related Air Pollution and Parkinson Disease Polygenic Risk Score. JAMA network open Kwon, D., Paul, K. C., Kusters, C., Wu, J., Bronstein, J. M., Lill, C. M., Ketzel, M., Raachou-Nielsen, O., Hansen, J., Ritz, B. 2025; 8 (3): e250854

  Abstract

  Genetic and environmental factors are linked to Parkinson disease (PD), but the role of genetic susceptibility in the association between traffic-related air pollution (TRAP) and PD remains unclear.To assess the gene-environment interaction between the polygenic risk score (PRS) for PD and long-term TRAP exposure and to estimate the joint effect with PD risk.This population-based case-control study used a meta-analytical assessment of studies conducted in central California and Denmark. The Parkinson Environment and Genes (PEG) study in California (June 1, 2000, to July 31, 2017) included 634 patients with PD and 733 controls; the Parkinson Disease in Denmark (PASIDA) study (January 1, 2006, to December 31, 2017) included 966 patients with PD and 1045 controls. Data were analyzed from July 1 to October 31, 2024.PRS was computed by summing the effect estimates of well-known risk alleles from an existing genome-wide association study's summary statistics using participants' genetic arrays. TRAP exposure was estimated using dispersion models to calculate long-term exposure (10- or 15-year means with a 5-year lag) to traffic-related pollutants (represented by carbon monoxide [CO] levels) at participants' residences.The main outcome was diagnosis of PD. Using multivariable logistic regression, PD risk was estimated from interactions between PRS (per SD) and TRAP exposure (per IQR), with joint effects based on low (quartiles 1-3) and high (quartile 4) exposure levels.A total of 1600 patients with PD (mean [SD] age, 65.1 [9.9] years; 990 [61.9%] male) and 1778 controls (mean [SD] age, 64.5 [10.3] years; 992 [55.8%] male) were included. Meta-analytical estimates suggest that both higher PRS and increased TRAP exposure increased PD risk, with an interaction effect estimate of 1.06 (95% CI, 1.00-1.12). Joint effect analysis indicated that individuals with both high PRS and high TRAP exposure were at greatest risk of PD (odds ratio, 3.05; 95% CI, 2.23-4.19) compared with the reference group with a low PRS and low TRAP exposure, suggesting a synergistic effect.In this gene-environment interaction study, a combination of long-term air pollution exposure and genetic susceptibility strongly contributed to the risk of developing PD. Widespread exposure to air pollution makes TRAP an important modifiable risk factor affecting large populations globally, particularly individuals with genetic vulnerability.

  View details for DOI 10.1001/jamanetworkopen.2025.0854

  View details for PubMedID 40094665

  View details for PubMedCentralID PMC11915066

• Regulatory T-Cells During Pregnancy Relate to Women's Own Childhood History of Microbial Exposure. American journal of human biology : the official journal of the Human Biology Council Fox, M. M., Hassan, A., Wiley, K. S., Kwon, D., Knorr, D. A. 2025; 37 (3): e70013

  Abstract

  Previous studies found that children with siblings, farm residence, and other proxies of greater microbial contacts had lower rates of hyper-responsive immune disorders. Yet, scientific debate persists regarding whether the human immune system is educated in early life primarily as a function of pathogenic or benign microbial exposures, or both. Furthermore, pregnancy relies on women's intrinsic immunosuppressive function, yet it remained unknown how immunoregulation in pregnant women relates to early-life microbial exposures. Here, we conduct a preliminary examination of whether childhood microbial exposures prime women's pregnancy-related immunoregulatory capacity.We administered retrospective questionnaires to estimate 55 pregnant women's early-life exposure to pathogenic (e.g., illness) and benign (e.g., pets; rural residence) microbes. Tolerogenic regulatory T-cells (Tregs) and Treg subtypes were measured by flow cytometry from peripheral blood.Results show that proxies for both pathogenic and benign exposures were positively associated with Treg concentrations.These findings offer insights that may help elucidate the relative contributions of early-life pathogenic ("hygiene hypothesis") and benign ("old friends hypothesis") microbial exposures toward the expansion of the Treg compartment. Human evolutionary history is characterized by changing microbial exposures as human residency patterns, living environments, and subsistence strategies changed. In this context, our findings suggest the possibility of less gestational pathology in human evolutionary past conditions typified by richer diversity of microbial exposure.

  View details for DOI 10.1002/ajhb.70013

  View details for PubMedID 40022470

  View details for PubMedCentralID PMC12001746

• Regulatory B-Cells Are Associated Negatively With Regulatory T-Cells and Positively With Cytokines in Peripheral Blood of Pregnant Women. American journal of reproductive immunology (New York, N.Y. : 1989) Wiley, K. S., Martínez, L. E., Kwon, D., Knorr, D. A., Epeldegui, M., Fox, M. M. 2025; 93 (2): e70027

  Abstract

  Regulatory B-cells (Bregs, CD19+CD24hiCD38hi) are a specialized B-cell subset that suppresses immune responses and potentially contribute to the maintenance of an immune-privileged environment for fetal development during pregnancy. However, little is known about the surrounding immunological environment of Bregs in gestational physiology. The relationship of regulatory T-cells (Tregs, CD4+CD25hiCD127loFoxP3+) to Bregs in coordinating immunoregulation during pregnancy is unknown. We aimed to determine whether peripheral concentrations of Bregs and/or PD-L1-expressing Bregs correlated with Tregs and cytokines during pregnancy.Peripheral blood samples were obtained from 29 pregnant women at mean 12 weeks' gestation. Participants were age ≥ 18, self-identified as Latina/Hispanic, and N = 12 primigravid. Peripheral blood mononuclear cells were isolated, stained, and analyzed by flow cytometry to determine percentages of Tregs from CD4+ T-cells and five Treg subsets defined by immune checkpoint markers, and Bregs and PD-L1+ Bregs from total B-cells. Levels of 13 cytokines were measured on a Meso Scale Discovery multiplex platform.Bregs positively correlated with pro-inflammatory cytokine interleukin (IL)-6. PD-L1+ Bregs positively correlated with T-cell suppressive cytokine IL-10. PD-L1+ Bregs negatively correlated with Tregs and Helios+, CTLA-4+, PD-1+, TIGIT+, and TIM3+ Tregs. For primigravida, PD-L1+ Bregs correlated positively with IL-10 and negatively with Helios+ and TIGIT+ Tregs. For multigravida, PD-L1+ Bregs correlated positively with IL-8 and negatively with Helios+, CTLA-4+, PD-1+, and TIGIT+ Tregs.This study provides insight into the immunosuppressive role of Bregs and PD-L1+ Bregs during human pregnancy. Our results suggest that PD-L1+ Bregs can employ suppressive mechanisms to limit pro-inflammatory responses in primigravida.

  View details for DOI 10.1111/aji.70027

  View details for PubMedID 39854121

  View details for PubMedCentralID PMC12001748

• Association between ultra-processed food intake and biological ageing in US adults: findings from National Health and Nutrition Examination Survey (NHANES) 2003-2010. Age and ageing Cardoso, B. R., Liu, J., Machado, P., Kwon, D., Belsky, D. W., Martinez Steele, E. 2024; 53 (12)

  Abstract

  The association between ultra-processed food (UPF) intake and markers of biological ageing has been scarcely investigated, despite the evident adverse health effects associated with UPF. This study aimed to test the association between UPF intake and biological ageing, and evaluate how much of this association is accounted for by overall diet quality.This cross-sectional study assessed 16 055 participants aged 20-79 years (51% women, 46 ± 0.3 years) from the National Health and Nutrition Examination Survey (NHANES) 2003-2010. Dietary UPF intake was assessed using the Nova system. Values were expressed as % of total energy intake and were denominated as a continuous variable and in quintiles. Diet quality was assessed with the American Heart Association 2020 and the Healthy Eating Index 2015. Biological ageing was assessed using the PhenoAge algorithm.For each 10% of energy intake accounted for by UPF, participants were 0.21 (95%CI 0.16-0.26) years biologically older in terms of PhenoAge. As compared to participants in the lowest UPF quintile (≤39%), those in the highest UPF quintile (68-100%) were 0.86 (95% CI 0.55, 1.16) years older (P-for-trend across quintiles ≤0.001). Adherence to a healthy diet moderately attenuated the relationship between UPF and PhenoAge (adjusted β = 0.14 per 10% increment of UPF).Adults with higher UPF tended to be biologically older. This association is partly independent of diet quality, suggesting that food processing may contribute to biological ageing acceleration. Our findings point to a compelling reason to target UPF consumption to promote healthier ageing.

  View details for DOI 10.1093/ageing/afae268

  View details for PubMedID 39657624

  View details for PubMedCentralID PMC11631094

• Association of pica with cortisol and inflammation among Latina pregnant women. American journal of human biology : the official journal of the Human Biology Council Kwon, D., Knorr, D. A., Wiley, K. S., Young, S. L., Fox, M. M. 2024; 36 (5): e24025

  Abstract

  Pica, the urge to consume items generally not considered food, such as dirt, raw starch, and ice, are particularly common among pregnant women. However, the biology of pica in pregnancy is not well understood. Therefore, this study aimed to assess how pica relates to endocrine stress and immune biomarkers in a cohort of pregnant Latina women in Southern California. Thirty-four women completed a structured pica questionnaire. Maternal urinary cortisol and plasma cytokine levels were measured between 21 and 31 weeks' gestation. Associations between pica during pregnancy and biomarkers were assessed using linear regression models adjusting for gestational age. Twelve (35.3%) of the pregnant women reported pica (geophagy and amylophagy) during pregnancy. In multivariate models, those who engaged in pica had higher levels of cortisol (β: 0.37, 95% CI: 0.01, 0.073) and lower levels of IL-1β (β: -0.06, 95% CI: -0.11, -0.02), IL-8 (β: -0.30, 95% CI: -0.56, -0.05), IL-21 (β: -0.35, 95% CI: -0.63, -0.08), and type-1 inflammation composite (β: -0.29, 95% CI: -0.44, -0.14) than women who did not engage in pica. These results suggest that biological stress and immune response differ for women with pica compared to those without. This study suggests novel physiological covariates of pica during pregnancy. Further research is needed to better understand the mechanisms and temporality underlying the observed associations between pica and endocrine and immune biomarkers.

  View details for DOI 10.1002/ajhb.24025

  View details for PubMedID 38050975

  View details for PubMedCentralID PMC11062838

• Diet and the gut microbiome in patients with Parkinson's disease. NPJ Parkinson's disease Kwon, D., Zhang, K., Paul, K. C., Folle, A. D., Del Rosario, I., Jacobs, J. P., Keener, A. M., Bronstein, J. M., Ritz, B. 2024; 10 (1): 89

  Abstract

  It has been suggested that gut microbiota influence Parkinson's disease (PD) via the gut-brain axis. Here, we examine associations between diet and gut microbiome composition and its predicted functional pathways in patients with PD. We assessed gut microbiota in fecal samples from 85 PD patients in central California using 16S rRNA gene sequencing. Diet quality was assessed by calculating the Healthy Eating Index 2015 (HEI-2015) based on the Diet History Questionnaire II. We examined associations of diet quality, fiber, and added sugar intake with microbial diversity, composition, taxon abundance, and predicted metagenomic profiles, adjusting for age, sex, race/ethnicity, and sequencing platform. Higher HEI scores and fiber intake were associated with an increase in putative anti-inflammatory butyrate-producing bacteria, such as the genera Butyricicoccus and Coprococcus 1. Conversely, higher added sugar intake was associated with an increase in putative pro-inflammatory bacteria, such as the genera Klebsiella. Predictive metagenomics suggested that bacterial genes involved in the biosynthesis of lipopolysaccharide decreased with higher HEI scores, whereas a simultaneous decrease in genes involved in taurine degradation indicates less neuroinflammation. We found that a healthy diet, fiber, and added sugar intake affect the gut microbiome composition and its predicted metagenomic function in PD patients. This suggests that a healthy diet may support gut microbiome that has a positive influence on PD risk and progression.

  View details for DOI 10.1038/s41531-024-00681-7

  View details for PubMedID 38649365

  View details for PubMedCentralID PMC11035608

• Regulatory T-cell phenotypes in prenatal psychological distress. Brain, behavior, and immunity Wiley, K. S., Kwon, D., Knorr, D. A., Fox, M. M. 2024; 116: 62-69

  Abstract

  Experiencing symptoms of psychological distress during pregnancy is common and has been linked to dysregulated immune functioning. In this context, immunoregulatory function is especially relevant because of its crucial role in establishment and maintenance of healthy pregnancy. However, little research has examined associations between women's prenatal psychological distress and immunoregulatory biomarkers. We investigated how symptoms of depression, anxiety, and stress relate to circulating levels of regulatory T-cells (Tregs).Pregnant Latina women were assessed at around 12 weeks of pregnancy (N = 82). These assessments included blood draws and self-report questionnaires assessing symptoms of depression, state anxiety, pregnancy-related anxiety, and perceived stress. Flow cytometry on PBMCs was used to quantify circulating Tregs, defined as CD3+CD4+CD25hiCD127loFoxP3+, and subpopulations positive for one of the following intra- or extracellular markers, CD45RA, CTLA-4, Helios, PD-1, TIM-3, and TIGIT. We collected 82 samples at 12 weeks. Multivariable linear regressions tested for associations between symptoms of psychological distress and Treg concentrations, adjusted for gestational age.State anxiety symptoms at 12 weeks were negatively associated with parent Treg cell levels (b = -4.02, p = 0.023) and subpopulations Helios+ (b = -3.29, p = 0.019) and TIM3+ (b = -3.17, p = 0.008). Perceived stress was negatively associated with the PD-1+ subpopulation at 12 weeks (b = -4.02, p = 0.023). Depression was not related to Tregs or the subpopulations.Our observation that symptoms of anxiety and stress are related to tolerogenic immunology suggests a possible biomechanism explaining correlations of maternal mood disorders with adverse outcomes for mothers and offspring.

  View details for DOI 10.1016/j.bbi.2023.11.033

  View details for PubMedID 38016492

  View details for PubMedCentralID PMC11402516

• Traffic-related air pollution and Parkinson's disease in central California. Environmental research Kwon, D., Paul, K. C., Yu, Y., Zhang, K., Folle, A. D., Wu, J., Bronstein, J. M., Ritz, B. 2024; 240 (Pt 1): 117434

  Abstract

  Prior studies suggested that air pollution exposure may increase the risk of Parkinson's Disease (PD). We investigated the long-term impacts of traffic-related and multiple sources of particulate air pollution on PD in central California.Our case-control analysis included 761 PD patients and 910 population controls. We assessed exposure at residential and occupational locations from 1981 to 2016, estimating annual average carbon monoxide (CO) concentrations - a traffic pollution marker - based on the California Line Source Dispersion Model, version 4. Additionally, particulate matter (PM2.5) concentrations were based on a nationwide geospatial chemical transport model. Exposures were assessed as 10-year averages with a 5-year lag time prior to a PD diagnosis for cases and an interview date for controls, subsequently categorized into tertiles. Logistic regression models were used, adjusting for various factors.Traffic-related CO was associated with an increased odds ratio for PD at residences (OR for T3 vs. T1: 1.58; 95% CI: 1.20, 2.10; p-trend = 0.02) and workplaces (OR for T3 vs. T1: 1.91; 95% CI: 1.22, 3.00; p-trend <0.01). PM2.5 was also positively associated with PD at residences (OR for T3 vs. T1: 1.62; 95% CI: 1.22, 2.15; p-trend <0.01) and workplaces (OR for T3 vs. T1: 1.85; 95% CI: 1.21, 2.85; p-trend <0.01). Associations remained robust after additional adjustments for smoking status and pesticide exposure and were consistent across different exposure periods.We found that long-term modeled exposure to local traffic-related air pollution (CO) and fine particulates from multiple sources (PM2.5) at homes and workplaces in central California was associated with an increased risk of PD.

  View details for DOI 10.1016/j.envres.2023.117434

  View details for PubMedID 37858688

  View details for PubMedCentralID PMC11232690

• Patterns and Life Course Determinants of Black-White Disparities in Biological Age Acceleration: A Decomposition Analysis. Demography Boen, C. E., Yang, Y. C., Aiello, A. E., Dennis, A. C., Harris, K. M., Kwon, D., Belsky, D. W. 2023; 60 (6): 1815-1841

  Abstract

  Despite the prominence of the weathering hypothesis as a mechanism underlying racialized inequities in morbidity and mortality, the life course social and economic determinants of Black-White disparities in biological aging remain inadequately understood. This study uses data from the Health and Retirement Study (n = 6,782), multivariable regression, and Kitagawa-Blinder-Oaxaca decomposition to assess Black-White disparities across three measures of biological aging: PhenoAge, Klemera-Doubal biological age, and homeostatic dysregulation. It also examines the contributions of racial differences in life course socioeconomic and stress exposures and vulnerability to those exposures to Black-White disparities in biological aging. Across the outcomes, Black individuals exhibited accelerated biological aging relative to White individuals. Decomposition analyses showed that racial differences in life course socioeconomic exposures accounted for roughly 27% to 55% of the racial disparities across the biological aging measures, and racial disparities in psychosocial stress exposure explained 7% to 11%. We found less evidence that heterogeneity in the associations between social exposures and biological aging by race contributed substantially to Black-White disparities in biological aging. Our findings offer new evidence of the role of life course social exposures in generating disparities in biological aging, with implications for understanding age patterns of morbidity and mortality risks.

  View details for DOI 10.1215/00703370-11057546

  View details for PubMedID 37982570

  View details for PubMedCentralID PMC10842850

• Diet quality and Parkinson's disease: Potential strategies for non-motor symptom management. Parkinsonism & related disorders Kwon, D., Folle, A. D., Del Rosario, I., Zhang, K., Paul, K. C., Keener, A. M., Bronstein, J. M., Ritz, B. 2023; 115: 105816

  Abstract

  Parkinson's disease (PD) is now considered a systemic disease, and some phenotypes may be modifiable by diet. We will compare the diet quality and intake of specific nutrients and food groups of PD patients with household and community controls to examine how diet may influence PD clinical features.We conducted a case-control study of 98 PD patients and 83 controls (household = 53; community = 30) in central California, assessing dietary habits over the past month and calculating the Healthy Eating Index (HEI)-2015. We employed multivariate logistic and linear regression analyses to assess associations between diet and PD status, PD symptom profiles, and medication, adjusting for relevant confounders.PD patients had a lower HEI score than controls, with an OR of 0.65 (95% CI: 0.45, 0.94) per 10-points increase in HEI. Lower-quality diet was characterized by higher intakes of carbohydrates, total and added sugars, and trans fats and lower intakes of fiber, folate, unsaturated fatty acids, protein, and fat. PD patients with chronic constipation had a 4.84 point lower HEI score than those without (β per 10-point in HEI: -0.48; 95% CI: -0.97, -0.00). Furthermore, patients on high dopamine agonist doses consumed more sugar than those on lower doses.PD patients consume a lower-quality diet compared to household and community controls. Dietary modifications may alleviate non-motor symptoms like constipation, and promoting a healthy diet should become a part of routine care and disease management for PD patients, with special attention on agonist-treated and hyposmic patients.

  View details for DOI 10.1016/j.parkreldis.2023.105816

  View details for PubMedID 37611510

  View details for PubMedCentralID PMC11121503

• How prenatal cortisol levels relate to grandmother-mother relationships among a cohort of Latina women. American journal of human biology : the official journal of the Human Biology Council Fox, M. M., Knorr, D. A., Kwon, D., Wiley, K. S., Parrish, M. H. 2023; 35 (7): e23883

  Abstract

  As part of the human reproductive strategy, mothers receive childcare assistance from others. For kin, allomothers are adaptively incentivized to provide assistance due to inclusive fitness benefits. Previous studies across a broad range of populations identify grandmothers as particularly consistent allomothers. Minimal attention has been paid to the possibility that allomothers may begin investing in offspring quality during the prenatal stage of life. Here, we innovate within the area of grandmother allocare research by examining the prenatal stage of life and biopsychosocial mechanisms by which prenatal grandmother effects may be enacted.Data derive from the Mothers' Cultural Experiences study, a cohort of 107 pregnant Latina women in Southern California. At <16 weeks' gestation, we administered questionnaires, collected morning urine samples, and measured cortisol by enzyme-linked immunosorbent assay, correcting for specific gravity. We measured the soon-to-be maternal and paternal grandmothers' relationship quality, social support, frequency of seeing each other, communicating, and geographic proximity to pregnant mothers, that is, their daughters and daughters-in-law. These measures were self-reported by the pregnant mothers. We assessed how grandmother constructs related to the pregnant women's depression, stress, anxiety, and cortisol levels.We observed benefits conferred by maternal grandmothers for mothers' prenatal mental health and lower cortisol levels. Paternal grandmothers also conferred mental health benefits to pregnant daughters-in-law, but higher cortisol levels.Our results suggest that grandmothers, especially maternal grandmothers, are able to improve their inclusive fitness by caring for pregnant daughters, and allomother support may positively impact prenatal health. This work extends the traditional cooperative breeding model by identifying a prenatal grandmother effect, and, by examining a maternal biomarker.

  View details for DOI 10.1002/ajhb.23883

  View details for PubMedID 36862026

  View details for PubMedCentralID PMC10474942

• Biological aging in maltreated children followed up into middle adulthood. Psychoneuroendocrinology Graf, G. H., Li, X., Kwon, D., Belsky, D. W., Widom, C. S. 2022; 143: 105848

  Abstract

  Childhood adversity has been linked to many indicators of shorter healthy lifespan, including earlier onset of disease and disability as well as early mortality. These observations suggest the hypothesis that childhood maltreatment may accelerate aging.To characterize the relationship between childhood maltreatment and accelerated biological aging in a prospective cohort of 357 individuals with documented cases of childhood maltreatment and 250 controls matched on demographic and socioeconomic factors.Cases were drawn from juvenile and adult court records from the years 1967 through 1971 in a large Midwest metropolitan geographic area. Cases were defined as having court-substantiated cases of childhood physical or sexual abuse, or neglect occurring at age 11 or younger. Controls were selected from the same schools and hospitals of birth and matched on age, sex, race, and approximate socioeconomic status. We compared biological aging in these two groups using two blood-chemistry algorithms, the Klemera-Doubal method Biological Age (KDM BA) and the PhenoAge. Algorithms were developed and validated in data from the National Health and Nutrition Examination Surveys (NHANES) using published methods and publicly available software.Participants (55% women, 49% non-White) had mean age of 41 years (SD=4). Those with court substantiated childhood maltreatment history exhibited more advanced biological aging as compared with matched controls, although this difference was statistically different for only the KDM BA measure (KDM BA Cohen's D=0.20, 95% CI=[0.03,0.36], p = 0.02; PhenoAge Cohen's D=0.09 95% CI=[-0.08,0.25], p = 0.296). In subgroup analyses, maltreatment effect sizes were larger for women as compared to men and for White participants as compared to non-White participants, although these differences were not statistically significant at the α= 0.05 level.As of midlife, effects of childhood maltreatment on biological aging are small in magnitude but discernible. Interventions to treat psychological and behavioral sequelae of exposure to childhood maltreatment, including in midlife adults, have potential to protect survivors from excess burden of disease, disability, and mortality in later life.

  View details for DOI 10.1016/j.psyneuen.2022.105848

  View details for PubMedID 35779342

• Alcohol use during pregnancy: findings from a gender-based violence survey in Mongolia. Archives of women's mental health Erdenetuya, B., Kwon, D., Choi, S., Choe, S. A. 2022; 25 (4): 789-795

  Abstract

  This study aimed to explore the risk factors for alcohol use during pregnancy in Mongolia, wherein high-risk alcohol use is prevalent. We analyzed nationwide data from the Gender-Based Violence (GBV) Survey of Mongolia conducted in 2017. We conducted an analysis restricted to 2714 women who had given birth within 5 years of the survey and who had responded to questions about their health-related behaviors during pregnancy. We assessed the association between alcohol use during pregnancy and pregnancy-related factors, including maternal age, educational attainment, history of abortion, smoking during pregnancy, unintended pregnancy, prior experience of sexual and physical violence, physical violence during pregnancy, and current binge drinking while also considering their residential region. Alcohol use during pregnancy was reported in 5.4% of the participating women. Unintended pregnancy for women (OR = 1.95, 95% confidence interval [CI]: 1.60, 2.38), abortion history (1.89, 95% CI: 1.60, 2.24), smoking during pregnancy (8.30, 95% CI: 6.60, 10.43), physical violence during pregnancy (2.22, 95% CI: 1.75, 2.81), and being a binge drinker (6.05, 95% CI: 3.63, 10.10) were associated with higher odds of alcohol use during pregnancy. Associations with maternal age, marital status, higher education, or multiparity were not evident. Our finding provides knowledge of risk factors for alcohol drinking among pregnant women and evidence for another harm of gender-based violence. This would contribute to the development of effective strategies for preventing antenatal exposure to alcohol in Mongolia.

  View details for DOI 10.1007/s00737-022-01242-8

  View details for PubMedID 35687163

  View details for PubMedCentralID 3645182

• Ambient Air Pollution and Kawasaki Disease in Korean Children: A Study of the National Health Insurance Claim Data. Journal of the American Heart Association Kwon, D., Choe, Y. J., Kim, S. Y., Chun, B. C., Choe, S. A. 2022; 11 (9): e024092

  Abstract

  Background Kawasaki disease (KD) is a systemic vasculitis of unknown etiology that primarily affects children under 5 years of age. Some researchers suggested a potential triggering effect of air pollution on KD, but the findings are inconsistent and limited by small sample size. We investigated the association between ambient air pollution and KD among the population of South Korea younger than 5 years using the National Health Insurance claim data between 2007 and 2019. Methods and Results We obtained the data regarding particulate matter ≤10 or 2.5 µm in diameter, nitrogen dioxide, sulfur dioxide, carbon monoxide, and ozone from 235 regulatory monitoring stations. Using a time-stratified case-crossover design, we performed conditional logistic regression to estimate odds ratios (OR) of KD according to interquartile range increases in each air pollutant concentration on the day of fever onset after adjusting for temperature and relative humidity. We identified 51 486 children treated for KD during the study period. An interquartile range increase (14.67 μg/m3) of particulate matter ≤2.5 µm was positively associated with KD at lag 1 (OR, 1.016; 95% CI, 1.004-1.029). An interquartile range increase (2.79 ppb) of sulfur dioxide concentration was associated with KD at all lag days (OR, 1.018; 95% CI, 1.002-1.034 at lag 0; OR, 1.022; 95% CI, 1.005-1.038 at lag 1; OR, 1.017; 95% CI, 1.001-1.033 at lag 2). Results were qualitatively similar in the second scenario of different fever onset, 2-pollutant model and sensitivity analyses. Conclusions In a KD-focused national cohort of children, exposure to particulate matter ≤2.5 µm and sulfur dioxide was positively associated with the risk of KD. This finding supports the triggering role of ambient air pollution in the development of KD.

  View details for DOI 10.1161/JAHA.121.024092

  View details for PubMedID 35475377

  View details for PubMedCentralID PMC9238605

• Social mobility and biological aging among older adults in the United States. PNAS nexus Graf, G. H., Zhang, Y., Domingue, B. W., Harris, K. M., Kothari, M., Kwon, D., Muennig, P., Belsky, D. W. 2022; 1 (2): pgac029

  Abstract

  Lower socioeconomic status is associated with faster biological aging, the gradual and progressive decline in system integrity that accumulates with advancing age. Efforts to promote upward social mobility may, therefore, extend healthy lifespan. However, recent studies suggest that upward mobility may also have biological costs related to the stresses of crossing social boundaries. We tested associations of life-course social mobility with biological aging using data from participants in the 2016 Health and Retirement Study (HRS) Venous Blood Study who provided blood-chemistry (n=9,255) and/or DNA methylation (DNAm) data (n=3,976). We quantified social mobility from childhood to later-life using data on childhood family characteristics, educational attainment, and wealth accumulation. We quantified biological aging using 3 DNAm "clocks" and 3 blood-chemistry algorithms. We observed substantial social mobility among study participants. Those who achieved upward mobility exhibited less-advanced and slower biological aging. Associations of upward mobility with less-advanced and slower aging were consistent for blood-chemistry and DNAm measures of biological aging, and were similar for men and women and for Black and White Americans (Pearson-r effect-sizes 0.2 for blood-chemistry measures and the DNAm GrimAge clock and DunedinPoAm pace-of-aging measures; effect-sizes were smaller for the DNAm PhenoAge clock). Analysis restricted to educational mobility suggested differential effects by racial identity; mediating links between educational mobility and healthy aging may be disrupted by structural racism. In contrast, mobility producing accumulation of wealth appeared to benefit White and Black Americans equally, suggesting economic intervention to reduce wealth inequality may have potential to heal disparities in healthy aging.

  View details for DOI 10.1093/pnasnexus/pgac029

  View details for PubMedID 35615471

• Testing Black-White Disparities in Biological Aging Among Older Adults in the United States: Analysis of DNA-Methylation and Blood-Chemistry Methods. American journal of epidemiology Graf, G. H., Crowe, C. L., Kothari, M., Kwon, D., Manly, J. J., Turney, I. C., Valeri, L., Belsky, D. W. 2022; 191 (4): 613-625

  Abstract

  Biological aging is a proposed mechanism through which social determinants drive health disparities. We conducted proof-of-concept testing of 8 DNA-methylation (DNAm) and blood-chemistry quantifications of biological aging as mediators of disparities in healthspan between Black and White participants in the 2016 wave of the Health and Retirement Study (n = 9,005). We quantified biological aging from 4 DNAm "clocks" (Horvath, Hannum, PhenoAge, and GrimAge clock), a DNAm pace-of-aging measure (DunedinPoAm), and 3 blood-chemistry measures (PhenoAge, Klemera-Doubal method biological age, and homeostatic dysregulation). We quantified Black-White disparities in healthspan from cross-sectional and longitudinal data on physical performance tests, self-reported limitations in activities of daily living, and physician-diagnosed chronic diseases, self-rated health, and survival. DNAm and blood-chemistry quantifications of biological aging were moderately correlated (Pearson's r = 0.1-0.4). The GrimAge clock, DunedinPoAm, and all 3 blood-chemistry measures were associated with healthspan characteristics (e.g., mortality effect-size hazard ratios were 1.71-2.32 per standard deviation of biological aging) and showed evidence of more advanced/faster biological aging in Black participants than in White participants (Cohen's d = 0.4-0.5). These measures accounted for 13%-95% of Black-White differences in healthspan-related characteristics. Findings suggest that reducing disparities in biological aging can contribute to building health equity.

  View details for DOI 10.1093/aje/kwab281

  View details for PubMedID 34850809

  View details for PubMedCentralID PMC9077113

• DunedinPACE, a DNA methylation biomarker of the pace of aging. eLife Belsky, D. W., Caspi, A., Corcoran, D. L., Sugden, K., Poulton, R., Arseneault, L., Baccarelli, A., Chamarti, K., Gao, X., Hannon, E., Harrington, H. L., Houts, R., Kothari, M., Kwon, D., Mill, J., Schwartz, J., Vokonas, P., Wang, C., Williams, B. S., Moffitt, T. E. 2022; 11

  Abstract

  Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Previously, we showed that quantification of the pace of biological aging from a DNA-methylation blood test was possible (Belsky et al., 2020). Here, we report a next-generation DNA-methylation biomarker of Pace of Aging, DunedinPACE (for Pace of Aging Calculated from the Epigenome).We used data from the Dunedin Study 1972-1973 birth cohort tracking within-individual decline in 19 indicators of organ-system integrity across four time points spanning two decades to model Pace of Aging. We distilled this two-decade Pace of Aging into a single-time-point DNA-methylation blood-test using elastic-net regression and a DNA-methylation dataset restricted to exclude probes with low test-retest reliability. We evaluated the resulting measure, named DunedinPACE, in five additional datasets.DunedinPACE showed high test-retest reliability, was associated with morbidity, disability, and mortality, and indicated faster aging in young adults with childhood adversity. DunedinPACE effect-sizes were similar to GrimAge Clock effect-sizes. In analysis of incident morbidity, disability, and mortality, DunedinPACE and added incremental prediction beyond GrimAge.DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience.This research was supported by US-National Institute on Aging grants AG032282, AG061378, AG066887, and UK Medical Research Council grant MR/P005918/1.

  View details for DOI 10.7554/eLife.73420

  View details for PubMedID 35029144

  View details for PubMedCentralID PMC8853656

• A toolkit for quantification of biological age from blood chemistry and organ function test data: BioAge. GeroScience Kwon, D., Belsky, D. W. 2021; 43 (6): 2795-2808

  Abstract

  Methods to quantify biological aging are emerging as new measurement tools for epidemiology and population science and have been proposed as surrogate measures for healthy lifespan extension in geroscience clinical trials. Publicly available software packages to compute biological aging measurements from DNA methylation data have accelerated dissemination of these measures and generated rapid gains in knowledge about how different measures perform in a range of datasets. Biological age measures derived from blood chemistry data were introduced at the same time as the DNA methylation measures and, in multiple studies, demonstrate superior performance to these measures in prediction of healthy lifespan. However, their dissemination has been slow by comparison, resulting in a significant gap in knowledge. We developed a software package to help address this knowledge gap. The BioAge R package, available for download at GitHub ( http://github.com/dayoonkwon/BioAge ), implements three published methods to quantify biological aging based on analysis of chronological age and mortality risk: Klemera-Doubal biological age, PhenoAge, and homeostatic dysregulation. The package allows users to parametrize measurement algorithms using custom sets of biomarkers, to compare the resulting measurements to published versions of the Klemera-Doubal method and PhenoAge algorithms, and to score the measurements in new datasets. We applied BioAge to safety lab data from the CALERIE™ randomized controlled trial, the first-ever human trial of long-term calorie restriction in healthy, non-obese adults, to test effects of intervention on biological aging. Results contribute evidence that CALERIE intervention slowed biological aging. BioAge is a toolkit to facilitate measurement of biological age for geroscience.

  View details for DOI 10.1007/s11357-021-00480-5

  View details for PubMedID 34725754

  View details for PubMedCentralID PMC8602613

• Associations of Loneliness and Social Isolation with Healthspan and Lifespan in the US Health and Retirement Study. The journals of gerontology. Series A, Biological sciences and medical sciences Crowe, C. L., Domingue, B. W., Graf, G. H., Keyes, K. M., Kwon, D., Belsky, D. W. 2021

  Abstract

  BACKGROUND: Loneliness and social isolation are emerging public health challenges for aging populations.METHODS: We followed N=11,302 US Health and Retirement Study (HRS) participants aged 50-95 from 2006-2014 to measure persistence of experiences of loneliness and exposure to social isolation. We tested associations of longitudinal loneliness and social isolation phenotypes with disability, morbidity, mortality, and biological aging through 2018.RESULTS: During follow-up, 18% of older adults met criteria for loneliness, with 6% meeting criteria at two or more follow-up assessments. For social isolation, these fractions were 21% and 8%. HRS participants who experienced loneliness and were exposed to social isolation were at increased risk for disease, disability, and mortality. Those experiencing persistent loneliness were at a 57% increased hazard of mortality compared to those who never experienced loneliness. For social isolation, the increase was 28%. Effect-sizes were somewhat larger for counts of prevalent activity limitations and somewhat smaller for counts of prevalent chronic diseases. Covariate adjustment for socioeconomic and psychological risks attenuated but did not fully explain associations. Older adults who experienced loneliness and were exposed to social isolation also exhibited physiological indications of advanced biological aging (Cohen's-d for persistent loneliness and social isolation=0.26 and 0.21, respectively). For loneliness, but not social isolation, persistence was associated with increased risk.CONCLUSION: Deficits in social connectedness prevalent in a national sample of US older adults were associated with morbidity, disability, and mortality and with more advanced biological aging. Bolstering social connectedness to interrupt experiences of loneliness may promote healthy aging.

  View details for DOI 10.1093/gerona/glab128

  View details for PubMedID 33963758

• Quantification of the pace of biological aging in humans through a blood test, the DunedinPoAm DNA methylation algorithm. eLife Belsky, D. W., Caspi, A., Arseneault, L., Baccarelli, A., Corcoran, D. L., Gao, X., Hannon, E., Harrington, H. L., Rasmussen, L. J., Houts, R., Huffman, K., Kraus, W. E., Kwon, D., Mill, J., Pieper, C. F., Prinz, J. A., Poulton, R., Schwartz, J., Sugden, K., Vokonas, P., Williams, B. S., Moffitt, T. E. 2020; 9

  Abstract

  Biological aging is the gradual, progressive decline in system integrity that occurs with advancing chronological age, causing morbidity and disability. Measurements of the pace of aging are needed as surrogate endpoints in trials of therapies designed to prevent disease by slowing biological aging. We report a blood-DNA-methylation measure that is sensitive to variation in pace of biological aging among individuals born the same year. We first modeled change-over-time in 18 biomarkers tracking organ-system integrity across 12 years of follow-up in n = 954 members of the Dunedin Study born in 1972-1973. Rates of change in each biomarker over ages 26-38 years were composited to form a measure of aging-related decline, termed Pace-of-Aging. Elastic-net regression was used to develop a DNA-methylation predictor of Pace-of-Aging, called DunedinPoAm for Dunedin(P)ace(o)f(A)ging(m)ethylation. Validation analysis in cohort studies and the CALERIE trial provide proof-of-principle for DunedinPoAm as a single-time-point measure of a person's pace of biological aging.

  View details for DOI 10.7554/eLife.54870

  View details for PubMedID 32367804

  View details for PubMedCentralID PMC7282814