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BACKGROUND: Although the relation of salt intake with blood pressure (BP) is linear, it is U-shaped for mortality and cardiovascular disease (CVD). This individual-participant meta-analysis explored whether the relation of hypertension, death or CVD with 24-h urinary sodium excretion (UVNA) or sodium-to-potassium (UNAK) ratio was modified by birth weight. METHODS: Families were randomly enrolled in the Flemish Study on Genes, Environment and Health Outcomes (1985-2004) and the European Project on Genes in Hypertension (1999-2001). Categories of birth weight, UVNA and UNAK (≤2500, >2500-4000, >4000 g; 4.6 g; and 2, respectively) were coded using deviation-from-mean coding and analyzed by Kaplan-Meier survival functions and linear and Cox regression. RESULTS: The study population was subdivided into the Outcome ( n = 1945), Hypertension ( n = 1460) and Blood Pressure cohorts ( n = 1039) to analyze the incidence of mortality and cardiovascular endpoints, hypertension and BP changes as function of UVNA changes. The prevalence of low/medium/high birth weight in the Outcome cohort was 5.8/84.5/9.7%. Over 16.7 years (median), rates were 4.9, 8 and 27.1% for mortality, CVD and hypertension, respectively, but were not associated with birth weight. Multivariable-adjusted hazard ratios were not significant for any endpoint in any of the birth weight, UVNA and UNAK strata. Adult body weight tracked with birth weight ( P

Background Hypertension and diabetes cause chronic kidney disease (CKD) and diastolic left ventricular dysfunction (DVD) as forerunners of disability and death. Home blood pressure telemonitoring (HTM) and urinary peptidomic profiling (UPP) are technologies enabling prevention. Methods UPRIGHT-HTM (Urinary Proteomics Combined with Home Blood Pressure Telemonitoring for Health Care Reform [NCT04299529]) is an investigator-initiated 5-year clinical trial with patient-centred design, which will randomise 1148 patients to be recruited in Europe, sub-Saharan Africa and South America. During the whole study, HTM data will be collected and freely accessible for patients and caregivers. The UPP, measured at enrolment only, will be communicated early during follow-up to 50% of patients and their caregivers (intervention), but only at trial closure in 50% (control). The hypothesis is that early knowledge of the UPP risk profile will lead to more rigorous risk factor management and result in benefit. Eligible patients, aged 55-75 years old, are asymptomatic, but have >= 5 CKD- or DVD-related risk factors, preferably including hypertension, type-2 diabetes, or both. The primary endpoint is a composite of new-onset intermediate and hard cardiovascular and renal outcomes. Demonstrating that combining UPP with HTM is feasible in a multicultural context and defining the molecular signatures of early CKD and DVD are secondary endpoints. Expected outcomes The expected outcome is that application of UPP on top of HTM will be superior to HTM alone in the prevention of CKD and DVD and associated complications and that UPP allows shifting emphasis from treating to preventing disease, thereby empowering patients. The authors gratefully acknowledge the enthusiasm of the patientsenrolled in UPRIGHT-HTM and the expert assistance of the consul-tants, residents and nursing staff supporting the trial at the clinicalsites. The Alliance for the Promotion of Preventive Medicine is anot-profitresearchinstitute(URL:www.appremed.org;Belgianregis-trationnumber,739849385),whichreceivedanon-bindinggrantfromOMRONHealthcareCo.Ltd.,Kyoto,Japan.UPRIGHT-HTMisaTopZprojectsupportedbyOMRONHealthcareCo.Ltd.,Kyoto,Japan

Data de publicació electrònica: 16-08-2022 Background: Inadequate sleep duration has been suggested as a chronic stressor associated with changes in telomere length (TL). This study aimed to explore the association between sleep duration and TL using the INMA birth cohort study data. Methods: A total of 1014 children were included in this study (cross-sectional: 686; longitudinal: 872). Sleep duration (h/day) was reported by caregivers at 4 years and classified into tertiles (7-10 h/day; >10-11 h/day; >11-14 h/day). Leucocyte TL at 4 and 7-9 years were measured using quantitative PCR methods. Multiple robust linear regression models, through log-level regression models, were used to report the % of difference among tertiles of sleep duration. Results: In comparison to children who slept between >10 and 11 h/day, those in the highest category (more than 11 h/day) had 8.5% (95% CI: 3.56-13.6) longer telomeres at 4 years. Longitudinal analysis showed no significant association between sleep duration at 4 years and TL at 7-9 years. Conclusion: Children who slept more hours per day had longer TL at 4 years independently of a wide range of confounder factors. Environmental conditions, such as sleep duration, might have a major impact on TL during the first years of life. Impact: Telomere length was longer in children with longer sleep duration (>11 h/day) independently of a wide range of confounder factors at age 4 and remained consistent by sex. Sleep routines are encouraged to promote positive child development, like the number of hours of sleep duration. Considering the complex biology of telomere length, future studies still need to elucidate which biological pathways might explain the association between sleep duration and telomere length. This study was funded by Instituto de Salud Carlos III/Agencia Estatal de Investigación, grant number PI18/00825 Project: ‘Dieta y actividad física en embarazo y tras el nacimiento y longitud del telómero en niños y adolescentes: Proyecto TeloDiPA’ and Unión Europea (FEDER) ‘Una manera de hacer Europa’; Generalitat Valenciana (GVA/2021/191); D.S.M. holds a postdoctoral grant by the Flemish Scientific Fund (FWO grant 12X9620N). In Sabadell, this study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds; PI12/01890 incl. FEDER funds; CP13/00054 incl. FEDER funds, PI15/00118 incl. FEDER funds, CPII18/00018), CIBERESP, Generalitat de Catalunya-CIRIT 1999SGR 00241, Generalitat de Catalunya-AGAUR (2009 SGR 501, 2014 SGR 822), Fundació La marató de TV3 (090430), Spanish Ministry of Economy and Competitiveness (SAF2012-32991 incl. FEDER funds), Agence Nationale de Securite Sanitaire de l’Alimentation de l’Environnement et du Travail (1262C0010), EU Commission (261357, 308333, 603794 and 634453). We acknowledge support from the Spanish Ministry of Science and Innovation and the State Research Agency through the ‘Centro de Excelencia Severo Ochoa 2019–2023’ Program (CEX2018-000806-S) and support from the Generalitat de Catalunya through the CERCA Program. In Asturias, this study was funded by ISCIII: PI04/2018, PI09/02311, PI13/02429, PI18/00909 co-funded by FEDER, ‘A way to make Europe’/‘Investing in your future’, Obra Social Cajastur/Fundación Liberbank and Universidad de Oviedo. In Valencia, this study was supported by grants from Instituto de Salud Carlos III [FIS-FEDER: 13/1944, 16/1288, 19/1338; Miguel Servet-FSE: MS15/0025, MSII20/0006 incl. FEDER funds], Generalitat Valenciana [AICO/2020/285] and Gobierno de España through Ministerio de Universidades under the grant CAS21/00008. The funders had no role in the design of the study; collection, management, analysis and interpretation of the data; preparation, review or approval and submission of the manuscript.

Additional file 1: Table S1. Overview over the identified studies investigating the interrelationships between the aging biomarkers DNA methylation age (DNAm age), global genome-wide DNA methylation (global methylation), telomere length (TL) and mitochondrial DNA content (mtDNA content).

Additional file 2: Text S1. Modified quantitative real-time PCR (qPCR) protocol for the determination of average relative telomere length and mtDNA content

Major depressive disorder (MDD) and adverse childhood experiences (ACE) are associated with poor physical and mental health in adulthood. One underlying mechanism might be accelerated cellular aging. For example, both conditions, MDD and ACE, have been related to a biological marker of cellular aging, accelerated shortening of telomere length (TL). Since MDD and ACE are confounded in many studies, we aimed with the current study to further disentangle the effects of MDD and ACE on TL using a full-factorial design including four carefully diagnosed groups of healthy participants and MDD patients with and without ACE (total N = 90, all without use of antidepressants). As dependent variable, TL was assessed in leukocytes. We found no group differences based on MDD and ACE exposure in TL. While TL was negatively associated with age and male sex, TL was not associated with any measure of severity of MDD, ACE or current stress. One possible explanation for our null result may be the comparatively good physical health status of our sample. Future research is needed to elucidate the relation of TL, MDD and ACE, taking potential effect modification by medication intake and physical health status into account.

Additional file 1: Study population. Each year, the ENVIRONAGE birth cohort [29] recruits around 150 singleton births, making it the largest birth cohort with a prospective follow-up in Belgium. Mothers without planned caesarean section and able to fill out a Dutch language questionnaire are eligible for the cohort. We collect biological samples (e.g. placental tissue, cord blood, maternal blood) and have access to all medical records during and after pregnancy, including anthropometric and foetal ultrasound data in addition to lifestyle factors derived from questionnaires filled out after delivery. After birth, we follow these children throughout different stages of life, with a first follow-up visit at the age of 4 – 6 years. During follow-up, we collect biological tissues, lifestyle and medical data, and perform clinical and neurological measurements of both the child and the mother. Measurement of mitochondrial DNA content. DNA was isolated from cord blood buffy coat, containing leukocytes, using the QIAamp DNA mini kit (Qiagen). The relative amount of mtDNA was measured by determining the ratio of two mitochondrial gene copy numbers (MTF3212/R3319 and MT-ND1) to a single-copy nuclear control gene (RPLP0) using a real-time quantitative polymerase chain reaction (qPCR). qPCR reactions were carried out in triplicate on a 384-well plate on the 7900HT Fast Real-Time PCR System (Applied Biosystems) in a 10 μl volume containing: 5 μl Fast SYBR Green (Applied Biosystems) mastermix, 0.3 μl of forward and reverse primers (300 nM) and 1.9 μl RNAse-free water and 6 ng DNA diluted in 2.5 μl RNAse-free water. Primer sequences for mitochondrial genes are reported elsewhere [16]. Six interrun calibrators and no-template controls were included in each qPCR run. The thermal cycling profile for the three targets was 10 min at 95 °C for activation of the polymerase enzyme and initial denaturation, followed by 40 cycles of 15 s at 94 °C for denaturation and 70 s at 58 °C for annealing and extension. After thermal cycling, the raw data were collected and processed using SDS 2.3 software (Applied Biosystems). The cycle quantification (Cq) values were normalized relatively to the RPLP0 gene using qBase + software (Biogazelle) taking into account the run-to-run differences [69]. Supplementary Table S1. Sex- and age-specific BMI cut-offs according to the International Obesity Task Force (IOTF) [30]. Supplementary Table S2. The trimester-specific association between prenatal PM2.5 exposure and childhood overweight (n = 368). Models were adjusted for gestational age, sex, ethnicity, maternal age, socioeconomic status, pre-pregnancy BMI, parity, smoking during pregnancy, and child’s age at follow-up. Trimester-specific estimates of change are given as odds ratio per 5 µg/m³ increment in PM2.5. Childhood overweight was defined based on WHO’s SD BMI scores: > sex- and age-specific BMI cut-offs according to the International Obesity Task Force (IOTF) [30]. Supplementary Table S3. Difference in childhood overweight in association with week-specific prenatal exposure to PM2.5 (n = 368). Models were adjusted for gestational age, sex, ethnicity, maternal age, socioeconomic status, pre-pregnancy BMI, parity, smoking during pregnancy, and child’s age at follow-up. Week-specific estimates of change are given as odds ratio per 5 µg/m³ increment in PM2.5. Supplementary Table S4. The trimester-specific association between prenatal PM2.5 exposure and cord blood MT-ND4L10550A>G heteroplasmy (n = 386). Models were adjusted for gestational age, sex, ethnicity, maternal age, SES, pre-pregnancy BMI, parity, season of delivery, smoking during pregnancy, cord blood mtDNA content, and maternal MT-ND4L10550A>G. Trimester-specific estimates are given as odds ratio per 5 µg/m³ increment in PM2.5. Supplementary Table S5. Difference in cord blood MT-ND4L10550A>G heteroplasmy in association with week-specific prenatal exposure to PM2.5 (n = 386). Models were adjusted for gestational age, sex, ethnicity, maternal age, socioeconomic status, pre-pregnancy BMI, parity, season of delivery, smoking during pregnancy, cord blood mtDNA content, and maternal MT-ND4L10550A>G. Week-specific estimates are given as odds ratio per 5 µg/m³ increment in PM2.5. Supplementary Table S6. Difference in cord blood MT-ND4L10550A>G in association with week-specific prenatal exposure to PM2.5 without mothers who smoked during pregnancy (n = 345). Models were adjusted for gestational age, sex, ethnicity, maternal age, socioeconomic status, pre-pregnancy BMI, parity, season of delivery, cord blood mtDNA content, and maternal MT-ND4L10550A>G. Week-specific estimates are given as odds ratio per 5 µg/m³ increment in PM2.5. Supplementary Figure S1. Flowchart study population selection. The ENVIRONAGE birth cohort included 1993 mother-child pairs until March 2021. The study population (n = 400) was recruited between February 2010 and December 2015. The association between prenatal PM2.5 exposure and cord blood MT-ND4L10550A>G was analyzed for 386 mother-newborn pairs. The association between prenatal PM2.5 exposure or cord blood MT-ND4L10550A>G and childhood overweight was analyzed for 368 mother-newborn pairs. The mediation analysis was performed on 355 mother-child pairs. Supplementary Figure S2. Variation in cord blood MT-ND4L10550A>G heteroplasmy level (n = 400), ordered by study ID.

Additional file 5: Figure S2. Pearson correlations between aging biomarkers in the subset of n = 98 boys

Additional file 4: Figure S1. Pearson correlations between aging biomarkers in the subset of n = 92 girls

Additional file 1: Text S1. TL, mtDNAc and single copy-gene reaction mixture and PCR cycling conditions. Table S1. The mental health indicators with their scores and uses. Table S2. Comparison of the characteristics of the 6,054 eligible BHIS participants that were included in the BHIS subset compared to the 1,838 eligible participants that were excluded from the BHIS subset. Table S3. Comparison of the characteristics of the 739 participants from the BHIS subset that were included in the BELHES subset compared to the 5,315 participants that were excluded from the BELHES subset. Table S4. Bivariate associations between the characteristics and telomere length (TL), mitochondrial DNA content (mtDNAc), the lifestyle score or psychological distress. Table S5. Results of the sensitivity analysis of the association between lifestyle and mental health. Table S6. Results of the sensitivity analysis of the association between lifestyle and the biomarkers of ageing. Table S7. Results of the sensitivity analysis of the association between mental health and the biomarkers of ageing. Fig. S1. Exclusion criteria. The BHIS subset consisted of 6,055 BHIS participants and the BELHES subset consisted of 739 BELHES participants. Fig. S2. Histogram of the lifestyle score. Fig. S3. Validation of the lifestyle score. ROC curve for the lifestyle score as a predictor for good to very good self-perceived health. The model was adjusted for age, sex, region, highest educational level in the household, household composition and country of birth.