1,721,108 research outputs found
Omgeving en leefstijfactoren: al vroeg in het leven van invloed op telomeerlengte
No full textTelomeren zij n de beschermende uiteinden van chromosomen en nemen in lengte af naarmate we verouderen. Telomeren zij n een indicator voor de gevoeligheid om ouderdomsgerelateerde ziekten te ontwikkelen. Verschillen in telomeerlengtes worden voornamelij k verklaard door een complex samen-spel van genetische, leefstij l-en omgevingsfactoren. Eerdere studies toonden aan dat een gezonde leefstij l belangrij k is in termen van ziektepreventie. Recent onderzoek toont aan dat leefstij l ook in verband wordt gebracht met essentiële biologische processen die betrokken zij n bij veroudering, zoals telomeerverkorting. Dit kan gedeeltelij k verklaren waarom er een verband is tussen leefstij l en ontwik-keling van ziekten. Dit benadrukt dat een gezonde leefstij l niet alleen direct bij draagt aan het voorkomen van ziekten, maar ook indirect via biologische processen die de veroudering reguleren en daarbij de gevoeligheid voor het ontstaan van ziekte verminderen. Deze omgevings-en leefstij lfactoren kunnen al voor de geboorte aanzienlij k invloed uitoefenen op de variatie in telomeerlengte bij pasgeborenen. Hoewel bij de geboorte ieder kind even oud is, is dat niet zo als we kij ken naar de biologische leeftij d op basis van de lengte van de telomeren. Met andere woorden, de lengte van de telomeren bij de geboorte vormt één van de mechanismen die verschillen in veroudering en ziektegevoeligheid gedurende het le-ven mee bepalen. Dit benadrukt het belang van een gezonde leefstij l en omgeving voor het bevorderen van een lang en gezond leven vanaf de preconceptie, niet alleen voor onszelf, maar ook voor toekomstige generaties. (NED TIJ DSCHR LEEFSTIJ LGENEESKD 2025;3(2):69-75) 1 PhD-student, 2 hoogleraar faculteit Wetenschappen, 3 gast FWO postdoctoraal onderzoeker, 4 Centrum voor Milieukunde, Universiteit Hasselt, Hasselt, België, 5 departement Maatschappelij ke Gezondheidszorg en Eerstelij nszorg, KU Leuven, Leuven, België. Correspondentie graag richten aan: dhr. prof. dr. T.S. Nawrot, Universiteit Hasselt, Centrum voor Milieukunde, Agoralaan gebouw D, 3590 Diepenbeek, België, tel: +32 490 57 70 13, e-mailadres: [email protected] Belangenconflict: geen gemeld. Financiële ondersteuning: D.S. Martens is houder van een postdoctoraatbeurs bij het Fonds Wetenschap-pelij k Onderzoek-Vlaanderen (FWO 12X9623N). Trefwoorden: gezondheid, leefstij lfactoren, preventie, telomeerlengte, veroudering
Maternal pre-pregnancy body mass index and newborn telomere length
No full textNewborn telomere length sets telomere length for later life. At birth, telomere length is highly variable among newborns and the environmental factors during in utero life for this observation remain largely unidentified. Obesity during pregnancy might reflect an adverse nutritional status affecting pregnancy and offspring outcomes, but the association of maternal pre-pregnancy body mass index (BMI) with newborn telomere length, as a mechanism of maternal obesity, on the next generation has not been addressed.sponsorship: The ENVIRONAGE birth cohort is supported by the EU Program "Ideas" (ERC-2012-StG 310898) and by the Flemish Scientific Fund (FWO, G073315N). (EU Program "Ideas"|ERC-2012-StG 310898, Flemish Scientific Fund (FWO)|G073315N)status: Publishe
Omgeving en leefstijfactoren: al vroeg in het leven van invloed op telomeerlengte
No full textTelomeren zij n de beschermende uiteinden van chromosomen en nemen in lengte af naarmate we verouderen. Telomeren zij n een indicator voor de gevoeligheid om ouderdomsgerelateerde ziekten te ontwikkelen. Verschillen in telomeerlengtes worden voornamelij k verklaard door een complex samen-spel van genetische, leefstij l-en omgevingsfactoren. Eerdere studies toonden aan dat een gezonde leefstij l belangrij k is in termen van ziektepreventie. Recent onderzoek toont aan dat leefstij l ook in verband wordt gebracht met essentiële biologische processen die betrokken zij n bij veroudering, zoals telomeerverkorting. Dit kan gedeeltelij k verklaren waarom er een verband is tussen leefstij l en ontwik-keling van ziekten. Dit benadrukt dat een gezonde leefstij l niet alleen direct bij draagt aan het voorkomen van ziekten, maar ook indirect via biologische processen die de veroudering reguleren en daarbij de gevoeligheid voor het ontstaan van ziekte verminderen. Deze omgevings-en leefstij lfactoren kunnen al voor de geboorte aanzienlij k invloed uitoefenen op de variatie in telomeerlengte bij pasgeborenen. Hoewel bij de geboorte ieder kind even oud is, is dat niet zo als we kij ken naar de biologische leeftij d op basis van de lengte van de telomeren. Met andere woorden, de lengte van de telomeren bij de geboorte vormt één van de mechanismen die verschillen in veroudering en ziektegevoeligheid gedurende het le-ven mee bepalen. Dit benadrukt het belang van een gezonde leefstij l en omgeving voor het bevorderen van een lang en gezond leven vanaf de preconceptie, niet alleen voor onszelf, maar ook voor toekomstige generaties. (NED TIJ DSCHR LEEFSTIJ LGENEESKD 2025;3(2):69-75) 1 PhD-student, 2 hoogleraar faculteit Wetenschappen, 3 gast FWO postdoctoraal onderzoeker, 4 Centrum voor Milieukunde, Universiteit Hasselt, Hasselt, België, 5 departement Maatschappelij ke Gezondheidszorg en Eerstelij nszorg, KU Leuven, Leuven, België. Correspondentie graag richten aan: dhr. prof. dr. T.S. Nawrot, Universiteit Hasselt, Centrum voor Milieukunde, Agoralaan gebouw D, 3590 Diepenbeek, België, tel: +32 490 57 70 13, e-mailadres: [email protected] Belangenconflict: geen gemeld. Financiële ondersteuning: D.S. Martens is houder van een postdoctoraatbeurs bij het Fonds Wetenschap-pelij k Onderzoek-Vlaanderen (FWO 12X9623N). Trefwoorden: gezondheid, leefstij lfactoren, preventie, telomeerlengte, veroudering
How sample handling distorts telomere studies
No full textTelomere length (TL) is investigated as a biomarker for aging and disease-susceptibility, but
measurement using quantitative polymerase chain reaction (qPCR) faces challenges in accuracy
and reproducibility. The potential impact of pre-analytical factors on TL measurements remains
underexplored. We evaluated the impact of delayed blood processing, a typical feature in population
studies. Blood samples from 35 adults were processed for buffy coat extraction either immediately or
kept at 4 °C and processed after three and seven days (total n=105). After processing, samples were
stored at -80 °C. Relative TL was measured via qPCR and expressed as T/S ratio. Strikingly, delayed
blood processing led to a significant increase in TL: the mean T/S ratio was 0.886±0.205 at day 0, rising
to 1.022±0.240 at day 3 (p=0.03) and to 1.190±0.205 at day 7 (p<0.001), corresponding to increases
of 15% and 34%, respectively. Notably, TL correlated inversely with DNA integrity. These findings
underscore the critical impact of delayed sample processing on TL measurements, emphasizing the
need for consistent pre-analytical protocols to ensure accurate and reliable research outcomes. The
impact of our findings is considerable as it may overshadow not only previously reported results but
also real biological differences in TL between studied groups of patients.This work is funded in part by the Research Foundation Flanders (grant number G072022N to JDB and grant
number 12X9623N to DSM)
Mitochondrial DNA methylation in placental tissue: a proof of concept study by means of prenatal environmental stressors
No full textWhile previous studies have demonstrated that prenatal exposure to environmental stressors is associated with mitochondrial DNA (mtDNA) methylation, more recent investigations are questioning the accuracy of the methylation assessment and its biological relevance. In this study, we investigated placental mtDNA methylation while accounting for methodological issues such as nuclear contamination, bisulphite conversion, and PCR bias. From the ENVIRONAGE birth cohort, we selected three groups of participants (n = 20/group). One group with mothers who smoked during pregnancy (average 13.2 cig/day), one group with high air pollutant exposure (PM2.5: 16.0 +/- 1.4 mu g/m(3), black carbon: 1.8 +/- 0.3 mu g/m(3)) and one control group (non-smokers, PM2.5: 10.6 +/- 1.7 mu g/m(3), black carbon: 0.9 +/- 0.1 mu g/m(3)) with low air pollutant exposure. DNA methylation levels were quantified in two regions of the displacement loop control region (D-loopandLDLR2) by bisulphite pyrosequencing. Additionally, we measured DNA methylation on nuclear genes involved in mitochondrial maintenance (PINK1, DNA2, andPOLG1) and assessed mtDNA content using qPCR. AbsoluteD-loopmethylation levels were higher for mothers that smoked extensively (+0.36%, 95% CI: 0.06% to 0.66%), and for mothers that were highly exposed to air pollutants (+0.47%, 95% CI: 0.20% to 0.73%). The relevance of our findings is further supported, asD-loopmethylation levels were correlated with placental mtDNA content (r = -0.40, p = 0.002) and associated with birth weight (-106.98 g, 95% CI: -209.60 g to -4.36 g for an IQR increase inD-loopmethylation). Most notably, our data demonstrates relevant levels of mtDNA methylation in placenta tissue, with significant associations between prenatal exposure to environmental stressors andD-loopmethylation.This work was supported by the Research Foundation Flanders [G082317N]; Research Foundation Flanders [N1518119].Janssen, BG (corresponding author), Hasselt Univ, Ctr Environm Sci, B-3590 Diepenbeek, Belgium.
[email protected]
Prenatal environment impacts telomere length in newborn dairy heifers
No full textTelomere length is associated with longevity and survival in multiple species. In human population-based studies, multiple prenatal factors have been described to be associated with a newborn's telomere length. In the present study, we measured relative leukocyte telomere length in 210 Holstein Friesian heifers, within the first ten days of life. The dam's age, parity, and milk production parameters, as well as environmental factors during gestation were assessed for their potential effect on telomere length. We found that for both primi- and multiparous dams, the telomere length was 1.16% shorter for each day increase in the calf's age at sampling (P = 0.017). The dam's age at parturition (P = 0.045), and the median temperature-humidity index (THI) during the third trimester of gestation (P = 0.006) were also negatively associated with the calves' TL. Investigating multiparous dams separately, only the calf's age at sampling was significantly and negatively associated with the calves' TL (P = 0.025). Results of the present study support the hypothesis that in cattle, early life telomere length is influenced by prenatal factors. Furthermore, the results suggest that selecting heifers born in winter out of young dams might contribute to increased longevity in dairy cattle
Cord blood eicosanoid signatures and newborn gestational age
No full textBeyond prostaglandins, the function of eicosanoids and other oxylipins in pregnancy and labor is poorly understood. In contrast to earlier work focusing on preterm infants, we investigated how oxylipin levels in newborns (measured in cord blood) vary during the last weeks of pregnancy in 190 mother-newborns (≥37 weeks of
gestation) of the ENVIRONAGE birth cohort, Belgium. We found increased levels of PGE2 (p = 0.003), PGF2α (p = 0.042), 8,9-DHET (p = 0.037), 11-HETE (p = 0.034), and 15-HETrE (p = 0.008) associated with full term pregnancy compared to early term labor. Furthermore, late vs early term was associated with increased levels of PGE2 (p = 0.012) and TXB2 (p = 0.033), while late vs full term was associated with decreased levels of 14,15-DHET (p = 0.029), 11,12-DHET (p = 0.033), and 5-HETE (p = 0.045). To summarize, nine eicosanoids, derived via three enzymatic pathways, were significantly associated with gestational age. Eight of these were derived from arachidonic acid, and one from dihomo-γ-linolenic acid.This study was supported by grants from the Swedish Research Councils Formas (2010-303) and VR (2014-6354), Marie Sklodowska Curie Actions, Cofund, Project INCA 600398, the European Research Council (ERC-2012-StG310898), ERA-NET ACCEPTED, and the Flemish Scientific Fund (FWO). The Swedish Metabolomics Centre (www.swedishmetabolomicscentre.se) is acknowledged for valuable assistance with the LC-MS/MS analysis
Exploring the impact of lifestyle and environmental exposures on appetite hormone levels in children and adolescents:An observational study
No full textBackground: Appetite hormones are considered a promising target in fighting obesity as impaired appetite hormone levels have already been associated with obesity. However, further insights in the drivers of appetite hormone levels are needed. Objectives: In this study, we investigated the associations of fasting appetite hormone levels with lifestyle and environmental exposures in children and adolescents. Methods: A total of 534 fasting blood samples were collected from children and adolescents (4-16y,50% boys) and appetite hormone levels (glucagon-like peptide-1 (GLP-1), peptide YY (PYY), pancreatic polypeptide (PP), leptin and ghrelin) were measured. Exposures included dietary quality (fiber-rich food intake, sugar propensity, fat propensity), psychosocial stress (happiness, negative emotions, negative life events and emotional problems), sleep duration, physical activity and environmental quality (long term black carbon (BC), particulate matter <2.5 μM (PM2.5), nitrogen dioxide (NO2) exposure, and green space in a 100 m and 2000 m radius around the residence). A multi-exposure score was calculated to combine all the exposures at study in one measure. Associations of individual exposures and multi-exposure score with appetite hormone levels were evaluated using linear mixed regression models adjusting for sex, age, socioeconomic status, waist-to-height ratio and multiple testing. Results: GLP-1 was associated with air pollution exposure (NO2 β* = -0.13, BC β* = -0.15, PM2.5 β* = -0.16, all p < 0.001). Leptin was associated with green space in a 100 m radius around the residence (β* = -0.11; p = 0.002). Ghrelin was associated with negative emotions (active ghrelin β* = -0.16; p = 0.04, total ghrelin β* = -0.23; p = 0.0051) and happiness (active ghrelin β* = 0.25; p < 0.001, total ghrelin β* = 0.26; p < 0.001). Furthermore, total ghrelin levels were associated with the multi-exposure score, reflecting unhealthy exposures and lifestyle (β* = -0.22; p = 0.036). Discussion: Our findings provide new insights into the associations of exposures with appetite hormone levels, which are of high interest for preventive obesity research. Further research is crucial to reveal the underlying mechanisms of the observed associations.</p
Genetic regulation of newborn telomere length is mediated and modified by DNA methylation
No full textTelomere length at birth determines later life telomere length and potentially predicts ageing-related diseases. However, the genetic and epigenetic settings of telomere length in newborns have not been analyzed. In addition, no study yet has reported how the interplay between genetic variants and genome-wide cytosine methylation explains the variation in early-life telomere length. In this study based on 281 mother-newborn pairs from the ENVIRONAGE birth cohort, telomere length and whole-genome DNA methylation were assessed in cord blood and 26 candidate single nucleotide polymorphism related to ageing or telomere length were genotyped. We identified three genetic variants associated with cord blood telomere length and 57 cis methylation quantitative trait loci (cis-mQTLs) of which 22 mQTLs confirmed previous findings and 35 were newly identified. Five SNPs were found to have significant indirect effects on cord blood telomere length via the mediating CpGs. The association between rs911874 (SOD2) and newborn telomere length was modified by nearby DNA methylation indicated by a significant statistical interaction. Our results suggest that DNA methylation in cis might have a mediation or modification effect on the genetic difference in newborn telomere length. This novel approach warrants future follow-up studies that are needed to further confirm and extend these findings.sponsorship: The ENVIRONAGE birth cohort is supported by grants from the European Research Council (Grant No. ERC-2012-StG310898), the Flemish Scientific Fund (FWO, Grant No. G073315N) and Kom Op Tegen Kanker (KOTK). DSM (FWO grant 12X9620N) is postdoctoral fellows of the Flanders Research Foundation. JH was partly funded by a postdoctoral research fellow grant from the Research Foundation-Flanders (FWO) (no. 12J9516N). This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 874583 (ATHLETE). (European Research Council, Flemish Scientific Fund (FWO)|ERC-2012-StG310898, Kom Op Tegen Kanker (KOTK)|G073315N, Kom Op Tegen Kanker (KOTK)|12X9620N, Research Foundation-Flanders (FWO), European Union|12J9516N, 874583)status: Publishe
Intrarenal arteriosclerosis and telomere attrition associate with dysregulation of the cholesterol pathway
No full textBACKGROUND: Recently, we demonstrated that arteriosclerosis in the smaller intrarenal arteries is associated with shorter telomere length, independently of history of cardiovascular events and calendar age. This suggests that intrarenal arteriosclerosis reflects replicative senescence, although the underlying molecular alterations remain unclear. RESULTS: Shorter intrarenal telomere length associated significantly with the presence of renal arteriosclerosis (T/S ratio 0.91±0.15 vs. 1.20±0.23 with vs. without arteriosclerosis, p=0.007, test cohort; T/S ratio 0.98 ±0.26 vs. 1.03 ±0.18 with vs. without arteriosclerosis, p=0.02, validation cohort). The presence versus absence of intrarenal arteriosclerosis was associated with differential expression of 1472 transcripts. Pathway analysis revealed enrichment of molecules involved in the superpathway of cholesterol biosynthesis as the most significant. The differential expression of these genes was confirmed in the independent validation cohort. Furthermore, the specific mRNA expression of the molecules in the superpathway of cholesterol biosynthesis associated significantly with intrarenal telomere length, and with history of cardiovascular events. INTERPRETATION: Our study illustrates that the superpathway of cholesterol biosynthesis interacts with the previously published association between shorter telomere length and arteriosclerosis. METHODS: This study included a test cohort of 40 consecutive kidney donors (calendar age 48.0 ± 15), with biopsies obtained prior to transplantation. Intrarenal leucocyte telomere length content was assessed using quantitative RT-PCR. Whole genome microarray mRNA expression analysis was performed using Affymetrix Gene 2.0 ST arrays. We investigated the associations between mRNA gene expression, telomere length as marker of replicative senescence, and intrarenal arteriosclerosis (Banff "cv" score = vascular fibrous intimal thickening = intimal hyperplasia) using adjusted multiple regression models. For biological interpretation and pathway overrepresentation analysis, we used Ingenuity Pathway Analysis. The significant pathways and genes were validated in an independent validation cohort of 173 kidney biopsies obtained prior to transplantation.status: Publishe
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