RESUMEN
While epigenetic age (EA) of mouse blood can be determined using DNA methylation analysis at three CpG sites in the Prima1, Hsf4 and Kcns1 genes it is not known whether this approach is useful for predicting vascular biological age. In this study we validated the 3-CpG estimator for age prediction in mouse blood, developed a new predictive model for EA in mouse aorta, and assessed whether epigenetic age acceleration (EAA) measured with blood and aorta samples correlates with age-dependent endothelial dysfunction. Endothelial function was characterized in vivo by MRI in 8-96-week-old C57BL/6 mice. Arterial stiffness was measured by USG-doppler. EA-related changes within 41 CpG sites in Prima1, Kcns1 and Hsf4 loci, were analyzed in the aorta and blood using bisulfite amplicon high-throughput sequencing. Progressive age-dependent endothelial dysfunction and changes in arterial stiffness were observed in 36-96-week-old C57BL/6 mice. Methylation levels of the investigated loci correlated with chronological age in blood and the aorta. The new model for EA estimation in aorta included three cytosines located in the Kcns1 and Hsf4, explained R2 = 87.8% of the variation in age, and predicted age with an mean absolute error of 9.6 weeks in the independent test set. EAA in the aorta was associated with endothelial dysfunction in the abdominal aorta and femoral artery what was consistent with the EAA direction estimated in blood samples. The rate of vascular biological ageing in mice, reflected by the age-dependent systemic endothelial dysfunction, could be estimated using DNA methylation measurements at three loci in aorta and blood samples.
Asunto(s)
Envejecimiento , Aorta , Metilación de ADN , Endotelio Vascular , Epigénesis Genética , Ratones Endogámicos C57BL , Rigidez Vascular , Animales , Metilación de ADN/genética , Envejecimiento/genética , Envejecimiento/fisiología , Endotelio Vascular/fisiopatología , Ratones , Rigidez Vascular/genética , Rigidez Vascular/fisiología , Masculino , Aorta/fisiopatología , Aorta/diagnóstico por imagen , Islas de CpG/genética , Imagen por Resonancia MagnéticaRESUMEN
The purpose of this paper is to formulate recommendations for the disclosure of biological traces in the laboratory and the handling of forensic evidence submitted for identification tests, recommended by the Polish Speaking Working Group of the International Society for Forensic Genetics. The paper organizes the knowledge of the most relevant stages of preliminary analysis of biological traces based on both literature sources and those resulting from years of research practice. Recommendations formulated in the course of multi-stage expert consultations contained in this study should be used in the development of laboratory procedures applied during the execution.
Asunto(s)
Genética Forense , Humanos , Polonia , Genética Forense/normas , Genética Forense/métodos , Genética Forense/legislación & jurisprudencia , Sociedades Científicas/normas , Dermatoglifia del ADN/normas , Revelación/normas , Revelación/legislación & jurisprudenciaRESUMEN
DNA methylation (DNAm) clocks hold promise for measuring biological age, useful for guiding clinical interventions and forensic identification. This study compared the commonly used DNAm clocks, using DNA methylation and SNP data generated from nearly 1000 human blood or buccal swab samples. We evaluated different preprocessing methods for age estimation, investigated the association of epigenetic age acceleration (EAA) with various lifestyle and sociodemographic factors, and undertook a series of novel genome-wide association analyses for different EAA measures to find associated genetic variants. Our results highlighted the Skin&Blood clock with ssNoob normalization as the most accurate predictor of chronological age. We provided novel evidence for an association between the practice of yoga and a reduction in the pace of aging (DunedinPACE). Increased sleep and physical activity were associated with lower mortality risk score (MRS) in our dataset. University degree, vegetable consumption, and coffee intake were associated with reduced levels of epigenetic aging, whereas smoking, higher BMI, meat consumption, and manual occupation correlated well with faster epigenetic aging, with FitAge, GrimAge, and DunedinPACE clocks showing the most robust associations. In addition, we found a novel association signal for SOCS2 rs73218878 (p = 2.87 × 10-8) and accelerated GrimAge. Our study emphasizes the importance of an optimized DNAm analysis workflow for accurate estimation of epigenetic age, which may influence downstream analyses. The results support the influence of genetic background on EAA. The associated SOCS2 is a member of the suppressor of cytokine signaling family known for its role in human longevity. The reported association between various risk factors and EAA has practical implications for the development of health programs to improve quality of life and reduce premature mortality associated with age-related diseases.