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Ciantar, J.

Publications and source records attributed to Ciantar, J..

3 recordsLinked to original sources

Male youth BMI is associated with epigenetic ageing of female descendants but not blood or sperm DNA methylation

Studies based on harvest records indicate that grandparental nutrition in youth is associated with the health traits of grandchildren in a sex-specific lineage. We investigated whether male early adulthood anthropometrics associate with epigenetic age, a measure of general well-being, and DNA methylation, a potential molecular inheritance mechanism, in three generations of descendants. Data on weight, height, BMI and chest circumference measured at military draft examinations (at age 18-24 yrs.) were retrieved from national archives for 1,013 men, herein referred to as Generation Archives (GA). The genome-wide DNA methylation of their descendants participating in the Young Finns Study (YFS) was measured from the blood and sperm from the children (59-80 yrs., nblood = 362, nsperm = 51), grandchildren (34-49 yrs., nblood = 421, nsperm = 98) and great-grandchildren (7-30 yrs., nblood = 200). The men's (GA) BMI had an inverse association with the epigenetic pace of ageing (DunedinPACE) of their daughters ({beta} = -0.01, p = 0.002, n = 169) and the daughters' daughters ({beta} = -0.01, p = 0.049, n = 126) but not with that of their male descendants. From within the YFS cohort, maternal, but not paternal, BMI at ages 13-34 also had an inverse association with the DunedinPACE of the immediate offspring. However, robust evidence for the inheritance mechanism was not found in the analyses between the anthropometric measurements of the GA men and the DNA methylation profiles in the blood and sperm of their descendants.

molecular biology↗

Traditional disease risk factors outperform epigenetic clocks as predictors of non-communicable disease morbidity in a middle-aged cohort

DNA methylation-based epigenetic clocks have been highlighted as promising biomarkers of ageing, and they have been shown to robustly predict morbidity and mortality. However, current literature is lacking a formal analysis of the increased prediction accuracy, or the added value, of the epigenetic clocks over traditional risk factors of common chronic diseases. Here, we have compared the most commonly used epigenetic clocks and traditional risk factors as predictors of incidence of ageing-associated non-communicable chronic disease in a 7-to-9-year follow-up in a middle-aged population cohort (n=1108, aged 34 to 49 years at baseline). In our cohort, a statistical model consisting of a combination of traditional risk factors outperforms any model including an epigenetic clock. The added value of epigenetic clock measurements over simple and affordable traditional risk factors should be clearly established, if epigenetic clocks are to be used in clinical settings or as tools of personal health monitoring.

molecular biology↗

Biological aging of different blood cell types

A biological age (BA) indicator is intended to capture detrimental age-related changes occurring with passing time. To date, the best-known and used BA indicators include DNA-methylation-based epigenetic ages (epigenetic clocks) and telomere length. The most common biological sample material for epidemiological aging studies is composed of different cell types, whole blood. We aimed to compare differences in BAs between blood cell types and assessed BA indicators cell type-specific associations with donors calendar age. Analysis on DNA methylation-based BA indicators including telomere length, methylation level at cg16867657 (a CpG-site in ELOVL2) and the Hannum, Horvath, DNAmPhenoAge and DunedinPACE epigenetic clocks was performed in 428 biological samples from 12 blood cell types. BA values were different (p<0.05) in the majority of pairwise comparisons between the cell types. Most cell types also displayed differences as compared to whole blood (p<0.05). Some of the observed differences persisted across blood donors calendar ages from 20 to 80 years (50-years-difference in DNAmPhenoAge between naive CD4+ T cells and monocytes), while others did not (up to four-fold difference in DunedinPACE values between monocytes and B cells). All BA indicators, except DunedinPACE, had mostly a very strong correlation with donors calendar age within a cell type. Our findings demonstrate that DNA methylation-based indicators of biological age exhibit cell type-specific characteristics, underscoring the importance of accounting for cell composition in related studies. Our results have implications for understanding the molecular mechanisms underlying epigenetic clocks and and provide guidance for utilizing them as indicators for success of aging interventions.

molecular biology↗