scholarly journals Integrating DNA-Methylation Measures of Biological Aging into Social Determinants of Health Research

2021 ◽  
Author(s):  
Laurel Raffington ◽  
Daniel Belsky

Purpose of Review: Acceleration of biological processes of aging is hypothesized to drive excess morbidity and mortality in socially disadvantaged populations. DNA methylation measures of biological aging provide tools for testing this hypothesis.Recent Findings: Next-generation DNA-methylation measures of biological aging developed to predict mortality risk and physiological decline are more predictive of morbidity and mortality than the original epigenetic clocks developed to predict chronological age. These new measures show consistent evidence of more advanced and faster biological aging in people exposed to socioeconomic disadvantage and may be able to record the emergence of socially-determined health inequalities as early as childhood. Next-generation DNA-methylation measures of biological aging also indicate race/ethnic disparities in biological aging. More research is needed on these measures in samples of non-Western and non-White populations.Summary: New DNA-methylation measures of biological aging open opportunities for refining inference about the causes of social disparities in health and devising policies to eliminate them. Further refining measures of biological aging by including more diversity in samples used for measurement development is a critical priority for the field.

2021 ◽  
Author(s):  
Laurel Raffington ◽  
Peter Tanksley ◽  
Liza Vinnik ◽  
Aditi Sabhlok ◽  
Megan Patterson ◽  
...  

Importance: Economic and racial inequality is linked to disparities in children's mental health. Biomarkers that reflect these social disparities are lacking. Objective: We examined the hypothesis that salivary DNA-methylation patterns of higher inflammation and faster pace of biological aging are economically, racially and ethnically stratified and are associated with child mental health. Design: The Texas Twin Project is an on-going, observational, longitudinal study that began in May 2012. Analyses were preregistered on May 7, 2021, and completed on August 23, 2021. Setting: The population-based study identified and recruited participants from public school rosters in the greater Austin area. Participants: Participants in the analytic data set included all participants that agreed to contribute DNA samples and whose samples were assayed by January 2021. Exposures: Family- and neighborhood-level socioeconomic inequality, racial and ethnic identities (White, Latinx, Black, Asian). Main Measure(s): Environmental exposures were analyzed in relation to salivary DNA-methylation profiles of higher inflammation (DNAm-CRP) and faster pace of biological aging (DunedinPoAm). Child internalizing problems, attention problems, aggression, rule-breaking, ADHD, oppositional defiant disorder, and conduct disorder were measured using parent-reports and self-reports on abbreviated versions of the Achenbach Child Behavior Checklist and Conners 3. The hypotheses being tested were formulated after data collection of the present data freeze and were pre-registered prior to analyses being conducted. Results: In a sample of N=1,183 8-to-19-year-olds (609 female, age M=13.38y), children's salivary DNA-methylation profiles and psychiatric symptoms differed by socioeconomic conditions, race and ethnicity. Children with more parent-reported internalizing symptoms had higher DNAm-CRP (r=0.15, 95% CI=0.05 to 0.25, P=0.004) and DunedinPoAm (r=0.15, CI=0.05 to 0.25, P=0.002), and children with more parent-reported aggression problems had higher DNAm-CRP (r=0.17, CI=0.04 to 0.31, P=0.013). DNAm-CRP partially mediated advantage of higher family socioeconomic status (16% of total effect) and White racial identity (12% of total effect) on reduced internalizing symptoms. DunedinPoAm also partially mediated advantage of White racial identity on internalizing (19% of total effect). Conclusions and Relevance: Socioeconomic and racial inequality are visible in children's epigenetic profiles of inflammation and the rate of biological aging in a manner that is tied to social disparities in mental health.


Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 311 ◽  
Author(s):  
Man-Kit Lei ◽  
Frederick X. Gibbons ◽  
Ronald L. Simons ◽  
Robert A. Philibert ◽  
Steven R. H. Beach

Smoking is one of the leading preventable causes of morbidity and mortality worldwide, prompting interest in its association with DNA methylation-based measures of biological aging. Considerable progress has been made in developing DNA methylation-based measures that correspond to self-reported smoking status. In addition, assessment of DNA methylation-based aging has been expanded to better capture individual differences in risk for morbidity and mortality. Untested to date, however, is whether smoking is similarly related to older and newer indices of DNA methylation-based aging, and whether DNA methylation-based indices of smoking can be used in lieu of self-reported smoking to examine effects on DNA methylation-based aging measures. In the current investigation we examine mediation of the impact of self-reported cigarette consumption on accelerated, intrinsic DNA methylation-based aging using indices designed to predict chronological aging, phenotypic aging, and mortality risk, as well as a newly developed DNA methylation-based measure of telomere length. Using a sample of 500 African American middle aged smokers and non-smokers, we found that a) self-reported cigarette consumption was associated with accelerated intrinsic DNA methylation-based aging on some but not all DNA methylation-based aging indices, b) for those aging outcomes associated with self-reported cigarette consumption, DNA methylation-based indicators of smoking typically accounted for greater variance than did self-reported cigarette consumption, and c) self-reported cigarette consumption effects on DNA methylation-based aging indices typically were fully mediated by DNA methylation-based indicators of smoking (e.g., PACKYRS from GrimAge; or cg05575921 CpG site). Results suggest that when DNA methylation-based indices of smoking are substituted for self-reported assessments of smoking, they will typically fully reflect the varied impact of cigarette smoking on intrinsic, accelerated DNA methylation-based aging.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Daniel L. McCartney ◽  
Josine L. Min ◽  
Rebecca C. Richmond ◽  
Ake T. Lu ◽  
Maria K. Sobczyk ◽  
...  

Abstract Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.


2021 ◽  
Vol 28 ◽  
Author(s):  
Chunyan Ao ◽  
Lin Gao ◽  
Liang Yu

: DNA methylation is an important mode of regulation in epigenetic mechanisms, and it is one of the research foci in the field of epigenetics. DNA methylation modification affects a series of biological processes, such as eukaryotic cell growth, differentiation and transformation mechanisms, by regulating gene expression. In this review, we systematically summarized the DNA methylation databases, prediction tools for DNA methylation modification, machine learning algorithms for predicting DNA methylation modification, and the relationship between DNA methylation modification and diseases such as hypertension, Alzheimer's disease, diabetic nephropathy, and cancer. An in-depth understanding of DNA methylation mechanisms can promote accurate prediction of DNA methylation modifications and the treatment and diagnosis of related diseases.


Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 429 ◽  
Author(s):  
Daniela Barros-Silva ◽  
C. Marques ◽  
Rui Henrique ◽  
Carmen Jerónimo

DNA methylation is an epigenetic modification that plays a pivotal role in regulating gene expression and, consequently, influences a wide variety of biological processes and diseases. The advances in next-generation sequencing technologies allow for genome-wide profiling of methyl marks both at a single-nucleotide and at a single-cell resolution. These profiling approaches vary in many aspects, such as DNA input, resolution, coverage, and bioinformatics analysis. Thus, the selection of the most feasible method according with the project’s purpose requires in-depth knowledge of those techniques. Currently, high-throughput sequencing techniques are intensively used in epigenomics profiling, which ultimately aims to find novel biomarkers for detection, diagnosis prognosis, and prediction of response to therapy, as well as to discover new targets for personalized treatments. Here, we present, in brief, a portrayal of next-generation sequencing methodologies’ evolution for profiling DNA methylation, highlighting its potential for translational medicine and presenting significant findings in several diseases.


Author(s):  
Cynthia G. Soto-Cardinault ◽  
Fátima Duarte-Aké ◽  
Clelia De-la-Peña ◽  
Elsa Góngora-Castillo

2018 ◽  
Vol 26 (3) ◽  
pp. 247-259 ◽  
Author(s):  
Nida’a K. AbuJbara ◽  
Jody A. Worley

Purpose This paper aims to highlight the importance of soft skills for leadership and offers recommendations for soft skill development training for the next generation of leaders. Design/methodology/approach An integrated review of current research literature was conducted on management, leadership and soft skills to develop recommendations for integrating the development of soft skills in leadership development training protocol. Findings A one-size-fits-all approach does not work for soft skills development or measurement. Each soft skill is defined differently and should be assessed based on different behavioral actions. Progress in this area of measurement development will make a great impact on the use of soft skills. The development of assessment tools for the different soft skills across professional disciplines is assumed to enhance other aspects of transformational leadership such as coaching and mentoring. Research limitations/implications Current strategies for the assessment and measurement of soft skills present an obstacle for including these skills in current leadership training models. Practical implications The paper includes implications for the development of soft skills for the next generation of leaders and offers recommendations for integrating the development of soft skills in leadership training programs. Originality/value This paper fulfills an identified need to study how soft skills can be measured and assessed. This is important given that specific skills vary across professional disciplines and organizational contexts.


2021 ◽  
Author(s):  
Jumpei Yamazaki ◽  
Yuki Matsumoto ◽  
Jaroslav Jelinek ◽  
Teita Ishizaki ◽  
Shingo Maeda ◽  
...  

Abstract Background: DNA methylation plays important functions in gene expression regulation that is involved in individual development and various diseases. DNA methylation has been well studied in human and model organisms, but only limited data exist in companion animals like dog. Results: Using methylation-sensitive restriction enzyme-based next generation sequencing (Canine DREAM), we obtained canine DNA methylation maps from 16 somatic tissues. In total, we evaluated 130,861 CpG sites. The majority of CpG sites were either highly methylated (>70%, 52.5%-64.6% of all CpG sites analyzed) or unmethylated (<30%, 22.5%-28.0% of all CpG sites analyzed) which are methylation patterns similar to other species. The overall methylation status of CpG sites across the 32 methylomes were remarkably similar. However, the tissue types were clearly defined by principle component analysis and hierarchical clustering analysis with DNA methylome. We found 6416 CpG sites located closely at promoter region of genes and inverse correlation between DNA methylation and gene expression of these genes. Conclusions: Our study provides basic dataset for DNA methylation profiles in dogs.


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