Association of Neighborhood Deprivation With Epigenetic Aging Using 4 Clock Metrics

Lawrence, Kaitlyn G.; Kresovich, Jacob K.; O’Brien, Katie M.; Hoang, Thanh T.; Xu, Zongli; Taylor, Jack A.; Sandler, Dale P.

doi:10.1001/jamanetworkopen.2020.24329

Cited by 69 publications

(80 citation statements)

References 59 publications

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“…2019 ) and physical activity and neighborhood SES in cross-sectional analyses of 2,700 women in the United States ( Kresovich et al. 2020 ; Lawrence et al. 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Surrounding Greenness and Biological Aging Based on DNA Methylation: A Twin and Family Study in Australia

et al. 2021

Environ Health Perspect

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Background: High surrounding greenness has many health benefits and might contribute to slower biological aging. However, very few studies have evaluated this from the perspective of epigenetics. Objectives: We aimed to evaluate the association between surrounding greenness and biological aging based on DNA methylation. Methods: We derived Horvath’s DNA methylation age (DNAmAge), Hannum’s DNAmAge, PhenoAge, and GrimAge based on DNA methylation measured in peripheral blood samples from 479 Australian women in 130 families. Measures of DNAmAge acceleration (DNAmAgeAC) were derived from the residuals after regressing each DNAmAge metric on chronological age. Greenness was represented by satellite-derived Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) metrics within 300-, 500-, 1,000-, and buffers surrounding participant addresses. Greenness-DNAmAgeAC associations were estimated using a within-sibship design fitted by linear mixed effect models, adjusting for familial clustering and important covariates. Results: Greenness metrics were associated with significantly lower DNAmAgeAC based on GrimAge acceleration, suggesting slower biological aging with higher greenness based on both NDVI and EVI in buffer areas. For example, each interquartile range increase in NDVI within was associated with a 0.59 (95% CI: 0.18, 1.01)–year decrease in GrimAge acceleration. Greenness was also inversely associated with three of the eight components of GrimAge, specifically, DNA methylation-based surrogates of serum cystatin-C, serum growth differentiation factor 15, and smoking pack years. Associations between greenness and biological aging measured by Horvath’s and Hannum’s DNAmAgeAC were less consistent, and depended on neighborhood socioeconomic status. No significant associations were estimated for PhenoAge acceleration. Discussion: Higher surrounding greenness was associated with slower biological aging, as indicated by GrimAge age acceleration, in Australian women. Associations were also evident for three individual components of GrimAge, but were inconsistent for other measures of biological aging. Additional studies are needed to confirm our results. https://doi.org/10.1289/EHP8793

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“…2019 ) and physical activity and neighborhood SES in cross-sectional analyses of 2,700 women in the United States ( Kresovich et al. 2020 ; Lawrence et al. 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Surrounding Greenness and Biological Aging Based on DNA Methylation: A Twin and Family Study in Australia

et al. 2021

Environ Health Perspect

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“…We encourage researchers to outline and differentiate the role of racism and not ancestry among these biomarkers. This is particularly important given the reported associations of epigenetic aging with social factors including diet [13,27], racial discrimination [28], neighborhood deprivation [29], and violence [30]. This study has some important limitations including small sample size and limited generalizability given that the cohort was comprised of only Polish women.…”

Section: Discussionmentioning

confidence: 98%

Long-term aspirin use and epigenetic mitotic clocks for cancer risk prediction: findings in healthy colon mucosa and recommendations for future epigenetic aging studies

Nwanaji‐Enwerem

Nze

2021

Epigenetics Commun.

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Background Despite the known role of mitosis in colorectal cancer, previous associations of long-term aspirin use with suppressed cancer-related epigenetic aging did not involve epigenetic mitotic clocks. We investigated these relationships using three epigenetic mitotic clocks developed for cancer risk prediction: EpiTOC, EpiTOC2, and MiAge. We utilized publicly available HumanMethylationEPIC BeadChip data from 112 healthy colon (proximal and distal) mucosal samples taken at baseline (T1) and at 10-years follow-up (T2) from a screening cohort of 28 Polish women (11 non-users and 17 long-term [≥ 2 years] aspirin users). Mitotic clock values were divided by chronological age at each timepoint to obtain intrinsic rates (IRs). We evaluated differences in residuals of the mitotic clock IRs taken from linear mixed effects models adjusted for BMI, polyp status, and DNA methylation batch. Findings EpiTOC, EpiTOC2, and MiAge were significantly correlated with chronological age (P < 0.05) with correlations ranging from 0.41 to 0.63. The EpiTOC, EpiTOC2, and MiAge clocks were strongly correlated with each other in proximal and distal samples (r > 0.79, P < 0.0001). We observed proximal within group median clock IR deceleration for EpiTOC (-0.0004 DNAm, P = 0.008), EpiTOC2 (− 16 cell divisions, P = 0.009), and MiAge (− 3 cell divisions, P = 0.002) for long-term aspirin users from T1 to T2 but not for non-users. In distal samples, only the long-term user MiAge IR was significantly deaccelerated (− 3 cell divisions, P = 0.009). Conclusions Our observed findings support previously reported longitudinal associations of aspirin use with deceleration of other epigenetic age measures in the proximal colon. Our mitotic clock results suggest that cell proliferation could play a role in some aspirin relationships with epigenetic aging. Furthermore, the findings provide added impetus for establishing gold standards for epigenetic aging and consensus guidelines for more comprehensive reporting in future epigenetic aging cancer studies.

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“…For example, in the Multi-Ethnic Study of Atherosclerosis (MESA) study, neighborhood characteristics have been found to in uence DNA methylation of genes involved in stress response and in ammation (32). More interestingly, using newly developed epigenetic clocks based on DNA methylation, Lawrence et al recently reported that residing in a neighborhood with a higher deprivation index had higher epigenetic age acceleration estimated by Hannum, PhenoAge, and GrimAge clocks (33).…”

Section: Discussionmentioning

confidence: 99%

Neighborhood disadvantage and biological aging biomarkers among breast cancer patients

Shen

Fuemmeler

Sheppard

et al. 2022

Preprint

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Living in a disadvantaged neighborhood is associated with adverse clinical outcomes among breast cancer patients, but the underlying pathway is still unclear. Limited evidence has suggested that accelerated biological aging may play an important role. In this study, using a sub-sample of 906 women with newly diagnosed breast cancer at M.D. Anderson, we examined whether levels of selected markers of biological aging (e.g., allostatic load, telomere length, and global DNA methylation) were affected by neighborhood disadvantage. The Area Deprivation Index (ADI) was used to determine the neighborhood disadvantage. Based on the median ADI at the national level, the study population was divided into low and high ADI groups. Overall, breast cancer patients from the high ADI group were more likely to be younger and non-Hispanic Black than those from the low ADI group (P < 0.001, respectively). They also more likely to have higher grade and poorly differentiated breast tumors (P = 0.029 and 0.019, respectively). For the relationship with markers, compared to the low ADI group, high ADI group had higher median levels of allostatic load (P = 0.046) and lower median levels of global DNA methylation (P < 0.001). Compared to their counterparts, those from the high ADI group were 20% more likely to have increased allostatic load and 51% less likely to have increased levels of global DNA methylation. In summary, we observed that levels of allostatic load and global DNA methylation are influenced by neighborhood disadvantage among breast cancer patients.

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Association of Neighborhood Deprivation With Epigenetic Aging Using 4 Clock Metrics

Cited by 69 publications

References 59 publications

Surrounding Greenness and Biological Aging Based on DNA Methylation: A Twin and Family Study in Australia

Surrounding Greenness and Biological Aging Based on DNA Methylation: A Twin and Family Study in Australia

Long-term aspirin use and epigenetic mitotic clocks for cancer risk prediction: findings in healthy colon mucosa and recommendations for future epigenetic aging studies

Neighborhood disadvantage and biological aging biomarkers among breast cancer patients

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