DNA methylation changes within the genome can be used to predict human age. However, the existing biological age prediction models based on DNA methylation are predominantly adult-oriented. We established a methylation-based age prediction model for children (9-212 months old) using data from 716 blood samples in 11 DNA methylation datasets. Our elastic net model includes 111 CpG sites, mostly in genes associated with development and aging. The model performed well and exhibited high precision, yielding a 98% correlation between the DNA methylation age and the chronological age, with an error of only 6.7 months. When we used the model to assess age acceleration in children based on their methylation data, we observed the following: first, the aging rate appears to be fastest in mid-childhood, and this acceleration is more pronounced in autistic children; second, lead exposure early in life increases the aging rate in boys, but not in girls; third, short-term recombinant human growth hormone treatment has little effect on the aging rate of children. Our child-specific methylation-based age prediction model can effectively detect epigenetic changes and health imbalances early in life. This may thus be a useful model for future studies of epigenetic interventions for age-related diseases.

Objectives: Heterotaxy syndrome is a recognized risk factor for surgical cardiac interventions. We evaluated the early- and middle-term results of a surgical intervention for patients with heterotaxy syndrome. Methods: A total of 42 patients with heterotaxy syndrome were enrolled (September 2008 to March 2015). Left and right atrial isomerism were identified in 26% (11 out of 42) and 74% of patients (31 out of 42), respectively. The median age of the patients at the time of surgery was 6.8 months (range: 5 days to 22.3 years). Biventricular repair was completed in 3 patients with left atrial isomerism. Seventeen out of 39 patients who were scheduled for single ventricular repair completed a modified Fontan procedure. Results: The hospital mortality rate was 4.7% (2 out of 42). Another 5 deaths occurred in the remaining survivors following hospital discharge with a follow-up duration of 45.8 ± 23.6 months (range: 13-111 months). The 1-year and 5-year survival rates were 88.1% (37/42) and 83.3% (35/42), respectively. Univariate analysis and multivariate analysis identified pulmonary venous obstruction and atrioventricular valve replacement as additional risk factors for mortality. Conclusions: Right ventricular bypass surgery remains the preferred palliative procedure for patients with heterotaxy syndrome. Based on the current results, the early- and middle-term outcomes are satisfactory.

Circulating microRNAs (miRNAs) have recently been indicated as practical and promising biomarkers for various diseases. However, circulating miRNAs have not been found to be biomarkers for pulmonary arterial hypertension (PAH) due to congenital heart disease. PAH is defined by a mean pulmonary arterial pressure (mPAP) >25 mmHg at rest. Blood samples and lung tissues were collected from patients with severe PAH due to ventricular septal defect (VSD) (PAH group, mPAP >45 mmHg, n=14) and patients with VSD but non-PAH (control group, mPAP <25 mmHg, n=16). Total RNA was extracted from the tissues and the plasma collected, and the different expression of miRNAs in tissues was detected by miRNA arrays. Selected miRNAs were also verified using real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Levels of miR-19a were quantified in the plasma of 30 patients. We also conducted receiver-operator characteristic curve analysis to evaluate the diagnostic ability of miR-19a; 78 microRNAs changed more than twofold. The changes in miR-19a, miR-130a, and miR-27b were also confirmed using qRT-PCR. miR-19a was then analyzed in prospectively collected plasma taken from both groups. The levels of miR-19a were significantly increased in the PAH samples. The value of the area under the receiver-operating characteristic curve was 0.781 (95% confidence interval, CI = 0.612-0.950, P < 0.0001) for the miR-19a assay. Circulating miR-19a turned out to be a pronounced marker for PAH. Our observations suggest that miR-19a expression is enhanced in PAH blood. Circulating miR-19a may be a novel biomarker for the diagnosis of PAH.

Knowing the biological age of the neonates enables us to evaluate and better understand the health and maturity comprehensively. However, because of dearth of biomarkers, it is difficult to quantify the neonatal biological age. Here we sought to quantify and assess the variability in biological age at birth and to better understand how the aging rates before birth are influenced by exposure in intrauterine period by employing a novel epigenetic biomarker of aging (epigenetic clock). We observed that the methylation age at birth was independent of the infant's sex but was significantly influenced by race. Partial correlation analysis showed a significant negative relationship between maternal socioeconomic status and infants' methylation age (r s = −0.48, P s = 0.005). A significant association with the risk of fast aging was observed for prenatal exposure to tobacco smoke with OR (95% CI) of 3.17 (1.05–9.56). Both estimated cell abundance measures and lymphocyte subpopulations in cord blood showed that tobacco exposed group exhibit an altered T cell compartment, specifically substantial loss of naive T cells. Present study provides the first evidence that common perinatal exposure (such as maternal smoking and lower socioeconomic status) may be important aging accelerators and substantial loss of naive T cells may play a role in the smoking-related fast aging phenomenon.

Mitochondrial dysfunction has been suggested to be the key factor in the development and progression of cardiac hypertrophy. The onset of mitochondrial dysfunction and the mechanisms underlying the development of cardiac hypertrophy (CH) are incompletely understood. The present study is based on the use of multiple bioinformatics analyses for the organization and analysis of scRNA-seq and microarray datasets from a transverse aortic constriction (TAC) model to examine the potential role of mitochondrial dysfunction in the pathophysiology of CH. The results showed that NADH:ubiquinone oxidoreductase core subunit S1- (Ndufs1-) dependent mitochondrial dysfunction plays a key role in pressure overload-induced CH. Furthermore, in vivo animal studies using a TAC mouse model of CH showed that Ndufs1 expression was significantly downregulated in hypertrophic heart tissue compared to that in normal controls. In an in vitro model of angiotensin II- (Ang II-) induced cardiomyocyte hypertrophy, Ang II treatment significantly downregulated the expression of Ndufs1 in cardiomyocytes. In vitro mechanistic studies showed that Ndufs1 knockdown induced CH; decreased the mitochondrial DNA content, mitochondrial membrane potential (MMP), and mitochondrial mass; and increased the production of mitochondrial reactive oxygen species (ROS) in cardiomyocytes. On the other hand, Ang II treatment upregulated the expression levels of atrial natriuretic peptide, brain natriuretic peptide, and myosin heavy chain beta; decreased the mitochondrial DNA content, MMP, and mitochondrial mass; and increased mitochondrial ROS production in cardiomyocytes. The Ang II-mediated effects were significantly attenuated by overexpression of Ndufs1 in rat cardiomyocytes. In conclusion, our results demonstrate downregulation of Ndufs1 in hypertrophic heart tissue, and the results of mechanistic studies suggest that Ndufs1 deficiency may cause mitochondrial dysfunction in cardiomyocytes, which may be associated with the development and progression of CH.