Browsing by Author "Kritchevsky, Stephen B."
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- Age-related variations in the methylome associated with gene expression in human monocytes and T cellsReynolds, Lindsay M.; Taylor, Jackson R.; Ding, Jingzhong; Lohman, Kurt; Johnson, Craig; Siscovick, David; Burke, Gregory L.; Post, Wendy; Shea, Steven; Jacobs, David R. Jr.; Stunnenberg, Hendrik G.; Kritchevsky, Stephen B.; Hoeschele, Ina; McCall, Charles E.; Herrington, David M.; Tracy, Russell P.; Liu, Yongmei (Springer Nature, 2014-11)Age-related variations in DNA methylation have been reported; however, the functional relevance of these differentially methylated sites (age-dMS) are unclear. Here we report potentially functional age-dMS, defined as age-and cis-gene expression-associated methylation sites (age-eMS), identified by integrating genome-wide CpG methylation and gene expression profiles collected ex vivo from circulating T cells (227 CD4+ samples) and monocytes (1,264 CD14+ samples, age range: 55-94 years). None of the age-eMS detected in 227 T-cell samples are detectable in 1,264 monocyte samples, in contrast to the majority of age-dMS detected in T cells that replicated in monocytes. Age-eMS tend to be hypomethylated with older age, located in predicted enhancers and preferentially linked to expression of antigen processing and presentation genes. These results identify and characterize potentially functional age-related methylation in human T cells and monocytes, and provide novel insights into the role age-dMS may have in the aging process.
- Metabolic Markers Demonstrate the Heterogeneity of Myosteatosis in Community-Dwelling Older Black Men from the Health ABC StudyFarsijani, Samaneh; Marron, Megan M.; Miljkovic, Iva; Baugh, Mary Elizabeth; Kritchevsky, Stephen B.; Newman, Anne B. (MDPI, 2021-04-07)Myosteatosis is a complex condition, associated with aging and diverse pathological conditions (e.g., diabetes), that contributes to mobility disability. Improved characterization of myosteatosis is required to develop targeted interventions to maintain muscle health in aging. We first determined the associations between plasma metabolites and intermuscular fat (IMF) in a cross-sectional analysis of 313 older Black men from Health ABC Study. Using partial correlation analysis, 34/350 metabolites were associated with IMF, the majority of which were lipids and organic acids. Next, we used Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), as an indicator of metabolic health to delineate the anthropometric, functional, and metabolic heterogeneity of myosteatosis in a case-control matching analysis. We categorized participants based on their IMF and HOMA-IR levels into: Low-IMF with Low- versus High-HOMA, as well as High-IMF with Low- versus High-HOMA. Among participants with similar levels of IMF, those who were metabolically unhealthy, i.e., with High HOMA-IR, had higher fat and lean mass, muscle strength, and had hyperglycemia, hypertriglyceridemia, hyperinsulinemia, and higher levels of plasma metabolites belonging to diacylglycerols, triacylglycerols, fatty acid and aminoacyl-tRNA biosynthesis pathways versus those with Low HOMA-IR. In summary, HOMA-IR delineates the heterogeneity of myosteatosis by distinguishing metabolically healthy versus unhealthy individuals.