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Article ; Online: Epigenetic age acceleration correlates with BMI in young adults.

Foster, Christy Anne / Barker-Kamps, Malcolm / Goering, Marlon / Patki, Amit / Tiwari, Hemant K / Mrug, Sylvie

Aging

2023 Volume 15, Issue 2, Page(s) 513–523

Abstract: Introduction: Obesity increases the risk of Type 2 diabetes, cardiovascular disease, several types of cancer, and other age-related disorders. Among older adults, obesity is also related to epigenetic age, typically measured with DNA methylation (DNAm). ...

Abstract	Introduction: Obesity increases the risk of Type 2 diabetes, cardiovascular disease, several types of cancer, and other age-related disorders. Among older adults, obesity is also related to epigenetic age, typically measured with DNA methylation (DNAm). Because less is known about obesity and epigenetic aging earlier in the lifespan, this study examined the relationship between obesity and DNAm in young adulthood and whether these relationships vary by sex. Methods: A cross-sectional community sample of 290 healthy young adults (mean age 27.39 years, 60% female; 80% African American, 18% White) had their BMI and waist circumference measured. Four epigenetic age estimators were derived from salivary DNA: Hannum DNAm, Horvath DNAm, Phenoage DNAm, and GrimAge DNAm. Sociodemographic covariates included age, sex, race, parental education, and income-to-needs ratio. Results: After adjusting for covariates, higher BMI and waist were associated with higher DNAm PhenoAge in both sexes, with a stronger effect on BMI in males (β = 0.35, Discussion: This study extends prior research by linking obesity with accelerated epigenetic aging in young adulthood, replicating the associations across two measures of obesity and four indices of salivary epigenetic aging. The results add to evidence that higher BMI accelerates aging early in the lifespan.
MeSH term(s)	Male ; Humans ; Female ; Young Adult ; Adult ; Aged ; Epigenesis, Genetic ; Diabetes Mellitus, Type 2/complications ; Cross-Sectional Studies ; Aging/genetics ; DNA Methylation ; Obesity/epidemiology ; Obesity/genetics ; Obesity/complications
Language	English
Publishing date	2023-01-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.204492
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Article ; Online: Neighborhood Disadvantage and Parenting in Early Adolescence Predict Epigenetic Aging and Mortality Risk in Adulthood.

Mrug, Sylvie / Barker-Kamps, Malcolm / Goering, Marlon / Patki, Amit / Tiwari, Hemant K

Journal of youth and adolescence

2023 Volume 53, Issue 2, Page(s) 258–272

Abstract: Youth who grow up in disadvantaged neighborhoods experience poorer health later in life, but little is known about the biological mechanisms underlying these effects and socioenvironmental factors that may protect youth from the biological embedding of ... ...

Abstract	Youth who grow up in disadvantaged neighborhoods experience poorer health later in life, but little is known about the biological mechanisms underlying these effects and socioenvironmental factors that may protect youth from the biological embedding of neighborhood adversity. This study tests whether supportive and consistent parenting buffers associations between neighborhood disadvantage in early adolescence and epigenetic aging in adulthood. A community sample from Birmingham, Alabama, USA (N = 343; 57% female; 81% Black, 19% White) was assessed in early adolescence (T1; ages 11 and 13) and adulthood (T2; age 27). At T1, neighborhood poverty was derived from census data and neighborhood disorder was reported by caregivers. Both youth and parents reported on parental discipline and nurturance. At T2, methylation of salivary DNA was used to derive a mortality risk index and Hannum, Horvath, PhenoAge, and GrimAge epigenetic age estimators. Regression analyses revealed that neighborhood disadvantage was associated with accelerated epigenetic aging and/or mortality risk only when combined with high levels of harsh and inconsistent discipline and low child-reported parental nurturance. These findings identify epigenetic aging and mortality risk as relevant mechanisms through which neighborhood adversity experienced in adolescence may affect later health; they also point to the importance of supportive and consistent parenting for reducing the biological embedding of neighborhood adversity in early adolescence.
MeSH term(s)	Humans ; Adolescent ; Female ; Adult ; Male ; Parenting ; Aging ; Residence Characteristics ; Neighborhood Characteristics ; Epigenesis, Genetic
Language	English
Publishing date	2023-09-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	186743-x
ISSN	1573-6601 ; 0047-2891
ISSN (online)	1573-6601
ISSN	0047-2891
DOI	10.1007/s10964-023-01863-x
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Zs.B 3120: Show issues

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Article ; Online: Impact of sustained calorie restriction and weight cycling on body composition in high-fat diet-fed male and female C57BL/6J mice.

Smith, Daniel L / Yang, Yongbin / Mestre, Luis M / Henschel, Beate / Parker, Erik / Dickinson, Stephanie / Patki, Amit / Allison, David B / Nagy, Tim R

Obesity (Silver Spring, Md.)

2024 Volume 32, Issue 5, Page(s) 959–968

Abstract: Objective: The objective of this study was to investigate body composition changes with weight cycling (WC) among adult C57BL/6J mice with diet-induced obesity.: Methods: A total of 555 single-housed mice were fed a high-fat diet ad libitum (AL) from ...

Abstract	Objective: The objective of this study was to investigate body composition changes with weight cycling (WC) among adult C57BL/6J mice with diet-induced obesity. Methods: A total of 555 single-housed mice were fed a high-fat diet ad libitum (AL) from 8 to 43 weeks of age. The 200 heaviest mice of each sex were randomized to the following four groups: ever obese (EO, continued AL feeding); obese weight loser (OWL, calorie-restricted); obese weight loser moderate (OWLM, body weight halfway between EO and OWL); and WC (diet restricted to OWL followed by AL refeeding cycles). Body weight and composition data were collected. Linear regression was used to calculate residuals between predicted and observed fat mass. Linear mixed models were used to compare diet groups. Results: Although weight loss and regain resulted in changes in body weight and composition, fat mass, body weight, and relative body fat were not significantly greater for the WC group compared with the EO group. During long-term calorie restriction, males (but not females) in the OWLM group remained relatively fatter than the EO group. Conclusions: WC did not increase body weight or relative fat mass for middle-aged, high-fat diet-fed adult mice. However, long-term moderate calorie restriction resulted in lower body weight but greater "relative" fat in male mice.
Language	English
Publishing date	2024-04-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2230457-5
ISSN	1930-739X ; 1071-7323 ; 1930-7381
ISSN (online)	1930-739X
ISSN	1071-7323 ; 1930-7381
DOI	10.1002/oby.24015
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Zs.A 4061: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Epigenetic Age Acceleration in Mothers and Offspring 4-10 Years after a Pregnancy Complicated by Gestational Diabetes and Obesity.

Kanney, Nita / Patki, Amit / Chandler-Laney, Paula / Garvey, W Timothy / Hidalgo, Bertha A

Metabolites

2022 Volume 12, Issue 12

Abstract: A known association exists between exposure to gestational diabetes mellitus (GDM) and epigenetic age acceleration (EAA) in GDM-exposed offspring compared to those without GDM exposure. This association has not been assessed previously in mothers with ... ...

Abstract	A known association exists between exposure to gestational diabetes mellitus (GDM) and epigenetic age acceleration (EAA) in GDM-exposed offspring compared to those without GDM exposure. This association has not been assessed previously in mothers with pregnancies complicated by GDM. A total of 137 mother-child dyads with an index pregnancy 4−10 years before study enrollment were included. Clinical data and whole blood samples were collected and quantified to obtain DNA methylation (DNAm) estimates using the Illumina MethylEPIC 850K array in mothers and offspring. DNAm age and age acceleration were evaluated using the Horvath and Hannum clocks. Multivariable linear regression models were performed to determine the association between EAA and leptin, high-density lipoprotein cholesterol (HDL-C), fasting glucose, fasting insulin, and HOMA-IR. Mothers with a GDM and non-GDM pregnancy had strong correlations between chronological age and DNAm age (r > 0.70). Offspring of GDM mothers had moderate to strong correlations, whereas offspring of non-GDM mothers had moderate correlations between chronological age and DNAm age. Association analyses revealed a significant association between EAA and fasting insulin in offspring (FDR < 0.05), while HDL-C was the only metabolic marker significantly associated with EAA in mothers (FDR < 0.05). Mothers in the GDM group had a higher predicted epigenetic age and age acceleration than mothers in the non-GDM group. The association between EAA with elevated fasting insulin in offspring and elevated HDL-C in mothers suggests possible biomarkers that can better elucidate the effects of exposure to a GDM pregnancy and future cardiometabolic outcomes.
Language	English
Publishing date	2022-12-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo12121226
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Article ; Online: Childhood Neighborhood Disadvantage, Parenting, and Adult Health.

Mrug, Sylvie / Barker-Kamps, Malcolm / Orihuela, Catheryn A / Patki, Amit / Tiwari, Hemant K

American journal of preventive medicine

2022 Volume 63, Issue 1 Suppl 1, Page(s) S28–S36

Abstract: Introduction: Growing up in disadvantaged neighborhoods is associated with poor adult health indicators. Consistent and supportive parenting plays a key role in life-long health, but it is not known whether positive parenting can mitigate the ... ...

Abstract	Introduction: Growing up in disadvantaged neighborhoods is associated with poor adult health indicators. Consistent and supportive parenting plays a key role in life-long health, but it is not known whether positive parenting can mitigate the relationship between neighborhood adversity and poor health. This study examines parenting as a moderator of the links between childhood neighborhood characteristics and adult health indicators. Methods: A sample of 305 individuals (61% female; 82% African American, 18% Caucasian) were assessed in childhood (T1; age 11 years; 2003‒2004) and adulthood (T2; age 27 years; 2018‒2021). At T1, neighborhood poverty was derived from census data; neighborhood disorder was reported by parents. Children reported on parental harsh discipline, inconsistent discipline, and parental nurturance. At T2, health outcomes included BMI, serum cortisol and C-reactive protein (CRP), and salivary DNA methylation index related to CRP. Regression models predicted T2 health outcomes from T1 neighborhood and parenting variables and their interactions, adjusting for clustering and confounders. Data were analyzed in 2021. Results: Neighborhood poverty was associated with lower cortisol, whereas neighborhood disorder was linked with CRP‒related DNA methylation. Multiple interactions between neighborhood and parenting variables emerged, indicating that adverse neighborhood conditions were only related to poor adult health when combined with inconsistent discipline and low parental nurturance. By contrast, warm and supportive parenting, consistent discipline, and to a lesser extent harsh discipline buffered children from poor health outcomes associated with neighborhood disadvantage. Conclusions: Interventions enhancing consistent and nurturing parenting may help to reduce the long-term associations of neighborhood disadvantage with poor health.
MeSH term(s)	Adult ; Black or African American ; Child ; Female ; Humans ; Hydrocortisone ; Male ; Neighborhood Characteristics ; Parenting ; Residence Characteristics
Chemical Substances	Hydrocortisone (WI4X0X7BPJ)
Language	English
Publishing date	2022-06-20
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	632646-8
ISSN	1873-2607 ; 0749-3797
ISSN (online)	1873-2607
ISSN	0749-3797
DOI	10.1016/j.amepre.2022.01.028
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Article ; Online: Omega-3 Fatty Acids and Risk of Ischemic Stroke in REGARDS.

Ament, Zsuzsanna / Patki, Amit / Bhave, Varun M / Kijpaisalratana, Naruchorn / Jones, Alana C / Couch, Catharine A / Stanton, Robert J / Rist, Pamela M / Cushman, Mary / Judd, Suzanne E / Long, D Leann / Irvin, M Ryan / Kimberly, W Taylor

Translational stroke research

2024

Abstract: We examined associations between lipidomic profiles and incident ischemic stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Plasma lipids (n = 195) were measured from baseline blood samples, and lipids were ... ...

Abstract	We examined associations between lipidomic profiles and incident ischemic stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Plasma lipids (n = 195) were measured from baseline blood samples, and lipids were consolidated into underlying factors using exploratory factor analysis. Cox proportional hazards models were used to test associations between lipid factors and incident stroke, linear regressions to determine associations between dietary intake and lipid factors, and the inverse odds ratio weighting (IORW) approach to test mediation. The study followed participants over a median (IQR) of 7 (3.4-11) years, and the case-cohort substudy included 1075 incident ischemic stroke and 968 non-stroke participants. One lipid factor, enriched for docosahexaenoic acid (DHA, an omega-3 fatty acid), was inversely associated with stroke risk in a base model (HR = 0.84; 95%CI 0.79-0.90; P = 8.33 × 10
Language	English
Publishing date	2024-04-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2541897-X
ISSN	1868-601X ; 1868-4483
ISSN (online)	1868-601X
ISSN	1868-4483
DOI	10.1007/s12975-024-01256-7
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Article ; Online: Sex-Associated Metabolites and Incident Stroke, Incident Coronary Heart Disease, Hypertension, and Chronic Kidney Disease in the REGARDS Cohort.

Couch, Catharine A / Ament, Zsuzsanna / Patki, Amit / Kijpaisalratana, Naruchorn / Bhave, Varun / Jones, Alana C / Armstrong, Nicole D / Cushman, Mary / Kimberly, W Taylor / Irvin, M Ryan

Journal of the American Heart Association

2024 Volume 13, Issue 9, Page(s) e032643

Abstract: Background: Sex disparities exist in cardiometabolic diseases. Metabolomic profiling offers insight into disease mechanisms, as the metabolome is influenced by environmental and genetic factors. We identified metabolites associated with sex and ... ...

Abstract	Background: Sex disparities exist in cardiometabolic diseases. Metabolomic profiling offers insight into disease mechanisms, as the metabolome is influenced by environmental and genetic factors. We identified metabolites associated with sex and determined if sex-associated metabolites are associated with incident stoke, incident coronary heart disease, prevalent hypertension, and prevalent chronic kidney disease. Methods and results: Targeted metabolomics was conducted for 357 metabolites in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) case-cohort substudy for incident stroke. Weighted logistic regression models were used to identify metabolites associated with sex in REGARDS. Sex-associated metabolites were replicated in the HyperGEN (Hypertension Genetic Epidemiology Network) and using the literature. Weighted Cox proportional hazard models were used to evaluate associations between metabolites and incident stroke. Cox proportional hazard models were used to evaluate associations between metabolites and incident coronary heart disease. Weighted logistic regression models were used to evaluate associations between metabolites and hypertension and chronic kidney disease. Fifty-one replicated metabolites were associated with sex. Higher levels of 6 phosphatidylethanolamines were associated with incident stroke. No metabolites were associated with incident coronary heart disease. Higher levels of uric acid and leucine and lower levels of a lysophosphatidylcholine were associated with hypertension. Higher levels of indole-3-lactic acid, 7 phosphatidylethanolamines, and uric acid, and lower levels of betaine and bilirubin were associated with chronic kidney disease. Conclusions: These findings suggest that the sexual dimorphism of the metabolome may contribute to sex differences in stroke, hypertension, and chronic kidney disease.
MeSH term(s)	Humans ; Male ; Female ; Renal Insufficiency, Chronic/epidemiology ; Renal Insufficiency, Chronic/metabolism ; Renal Insufficiency, Chronic/diagnosis ; Middle Aged ; Hypertension/epidemiology ; Coronary Disease/epidemiology ; Coronary Disease/metabolism ; Stroke/epidemiology ; Incidence ; Aged ; Metabolomics/methods ; Sex Factors ; United States/epidemiology ; Risk Factors ; Risk Assessment
Language	English
Publishing date	2024-04-30
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Multicenter Study
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.123.032643
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Article ; Online: Plasma Metabolites and Life's Simple 7 in REGARDS.

Kijpaisalratana, Naruchorn / Ament, Zsuzsanna / Patki, Amit / Bhave, Varun M / Jones, Alana C / Couch, Catharine A / Garcia Guarniz, Ana-Lucia / Cushman, Mary / Long, D Leann / Judd, Suzanne E / Irvin, M Ryan / Kimberly, W Taylor

Stroke

2024 Volume 55, Issue 5, Page(s) 1191–1199

Abstract: Background: The American Heart Association's Life's Simple 7 (LS7) is a health metric that captures important factors associated with cardiovascular and cerebrovascular health. Previous studies highlight the potential of plasma metabolites to serve as a ...

Abstract	Background: The American Heart Association's Life's Simple 7 (LS7) is a health metric that captures important factors associated with cardiovascular and cerebrovascular health. Previous studies highlight the potential of plasma metabolites to serve as a marker for lifestyle and health behavior that could be a target for stroke prevention. The objectives of this study were to identify metabolites that were associated with LS7 and incident ischemic stroke and mediate the relationship between the two. Methods: Targeted metabolomic profiling of 162 metabolites by liquid chromatography-tandem mass spectrometry was used to identify candidate metabolites in a stroke case-cohort nested within the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Weighted linear regression and weighted Cox proportional hazard models were used to identify metabolites that were associated with LS7 and incident ischemic stroke, respectively. Effect measures were based on a 1-SD change in metabolite level. Metabolite mediators were examined using inverse odds ratio weighting mediation analysis. Results: The study comprised 1075 ischemic stroke cases and 968 participants in the random cohort sample. Three out of 162 metabolites were associated with the overall LS7 score including guanosine (β, -0.46 [95% CI, -0.65 to -0.27]; Conclusions: We identified guanosine, cotinine, and acetylneuraminic acid that were associated with LS7, incident ischemic stroke, and mediated the relationship between LS7 and ischemic stroke.
Language	English
Publishing date	2024-03-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	80381-9
ISSN	1524-4628 ; 0039-2499 ; 0749-7954
ISSN (online)	1524-4628
ISSN	0039-2499 ; 0749-7954
DOI	10.1161/STROKEAHA.123.044714
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Article: Metabolite profiles and DNA methylation in metabolic syndrome: a two-sample, bidirectional Mendelian randomization.

Jones, Alana C / Ament, Zsuzsanna / Patki, Amit / Chaudhary, Ninad S / Srinivasasainagendra, Vinodh / Kijpaisalratana, Naruchorn / Absher, Devin M / Tiwari, Hemant K / Arnett, Donna K / Kimberly, W Taylor / Irvin, Marguerite R

Frontiers in genetics

2023 Volume 14, Page(s) 1184661

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2023-09-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2023.1184661
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Article ; Online: Gut microbiota-associated metabolites and risk of ischemic stroke in REGARDS.

Ament, Zsuzsanna / Patki, Amit / Bhave, Varun M / Chaudhary, Ninad S / Garcia Guarniz, Ana-Lucia / Kijpaisalratana, Naruchorn / Judd, Suzanne E / Cushman, Mary / Long, D Leann / Irvin, M Ryan / Kimberly, W Taylor

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

2023 Volume 43, Issue 7, Page(s) 1089–1098

Abstract: Several metabolite markers are independently associated with incident ischemic stroke. However, prior studies have not accounted for intercorrelated metabolite networks. We used exploratory factor analysis (EFA) to determine if metabolite factors were ... ...

Abstract	Several metabolite markers are independently associated with incident ischemic stroke. However, prior studies have not accounted for intercorrelated metabolite networks. We used exploratory factor analysis (EFA) to determine if metabolite factors were associated with incident ischemic stroke. Metabolites (n = 162) were measured in a case-control cohort nested in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, which included 1,075 ischemic stroke cases and 968 random cohort participants. Cox models were adjusted for age, gender, race, and age-race interaction (base model) and further adjusted for the Framingham stroke risk factors (fully adjusted model). EFA identified fifteen metabolite factors, each representing a well-defined metabolic pathway. Of these, factor 3, a gut microbiome metabolism factor, was associated with an increased risk of stroke in the base (hazard ratio per one-unit standard deviation, HR = 1.23; 95%CI = 1.15-1.31; P = 1.98 × 10
MeSH term(s)	Humans ; Gastrointestinal Microbiome ; Ischemic Stroke/etiology ; Stroke/etiology ; Risk Factors ; Diet/adverse effects ; Biomarkers ; Incidence
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-03-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604628-9
ISSN	1559-7016 ; 0271-678X
ISSN (online)	1559-7016
ISSN	0271-678X
DOI	10.1177/0271678X231162648
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