Project description:Changes in the DNA methylation (DNAm) landscape have been implicated in aging and cellular senescence. To unravel the role of specific DNAm patterns in late-life survival, we performed genome-wide methylation profiling in nonagenarians (n=111) and determined the performance of the methylomic predictors and conventional risk markers in a longitudinal setting. The survival model containing only the methylomic predictors was superior in terms of predictive accuracy compared with the models containing the conventional predictors body mass index and mini-mental state examination. At the 2.55-year follow-up, we identified 19 mortality-associated (false-discovery rate <0.5) CpG sites that mapped to genes functionally clustering around the nuclear factor kappa B (NF-κB) complex. Interestingly, none of the mortality-associated CpG sites overlapped with the established aging-associated DNAm sites. Our results are in line with previous findings on the role of NF-κB in controlling animal life spans and demonstrate the key role of this complex in human longevity.
Project description:BACKGROUND: Prediction models for old-age mortality have generally relied upon conventional markers such as plasma-based factors and biophysiological characteristics. However, it is unknown whether the existing markers are able to provide the most relevant information in terms of old-age survival or whether predictions could be improved through the integration of whole-genome expression profiles. METHODS: We assessed the predictive abilities of survival models containing only conventional markers, only gene expression data or both types of data together in a Vitality 90+ study cohort consisting of n = 151 nonagenarians. The all-cause death rate was 32.5% (49 of 151 individuals), and the median follow-up time was 2.55 years. RESULTS: Three different feature selection models, the penalized Lasso and Ridge regressions and the C-index boosting algorithm, were used to test the genomic data. The Ridge regression model incorporating both the conventional markers and transcripts outperformed the other models. The multivariate Cox regression model was used to adjust for the conventional mortality prediction markers, i.e., the body mass index, frailty index and cell-free DNA level, revealing that 331 transcripts were independently associated with survival. The final mortality-predicting transcriptomic signature derived from the Ridge regression model was mapped to a network that identified nuclear factor kappa beta (NF-?B) as a central node. CONCLUSIONS: Together with the loss of physiological reserves, the transcriptomic predictors centered around NF-?B underscored the role of immunoinflammatory signaling, the control of the DNA damage response and cell cycle, and mitochondrial functions as the key determinants of old-age mortality. The study consisted of 151 nonagenarians who were analyzed for genome-wide transcriptomic mortality predictors in a longitudinal setting.
Project description:Summer mortality of the Pacific oyster Crassostrea gigas is the result of a complex interaction between oysters, their environment and pathogens. Heredity appears to be a major factor determining the sensitivity of oysters to summer mortality, allowing resistant (R) and susceptible (S) lines to be produced. We conducted genome-wide expression profiling of R and S gonads during the 3-month period preceding a summer mortality event using a 9K cDNA microarray that we designed. This transcriptional analysis provides new indications to define markers for Quantitative Trait Loci searches and functional studies, and evaluates the potential role of each gene in the resistance to summer mortality
Project description:This study aimed to examine if early life exercise could normalize the reduced heart mass we have previously observed in the adult hearts from growth restricted rats. We investigated the molecular pathways using microarray analysis to explain how endurance exercise in early life might be regulating the sustained increase in heart mass we have observed in these rats in adulthood. At 5 weeks of age, male WKY rats were allocated to one of the following exercise treatments: remained sedentary with post mortem (PM) at 9 or 24 weeks, early exercise training (from 5-9 weeks of age) with PM at 9 or 24 weeks, or later exercise training (from 20-24 weeks of age) with PM at 24 weeks (n=8 males/group). Exercise training involved treadmill running 5 days/ week for 4 weeks. Running duration progressively increased from 20 up to 60 minutes per day, with the treadmill speed set at 15 m/min for the first week and 20 m/min thereafter. At 9 or 24 weeks of age rats were killed with an intraperitoneal injection of Ilium Xylazil-20 (30 mg/kg) and Ketamine (225 mg/kg). The rats in the 9 week old early exercise and 24 week old later exercise groups were killed 72 hours following the last bout of treadmill running. Total RNA was obtained from the whole-hearts for analysis Total RNA obtained from the hearts of WKY rats. Male offspring remained sedentary or underwent treadmill running from 5-9 weeks (early exercise) or 20-24 weeks of age (later exercise).
Project description:This study aimed to examine if early life exercise could normalize the reduced heart mass we have previously observed in the adult hearts from growth restricted rats. We investigated the molecular pathways using microarray analysis to explain how endurance exercise in early life might be regulating the sustained increase in heart mass we have observed in these rats in adulthood. At 5 weeks of age, male WKY rats were allocated to one of the following exercise treatments: remained sedentary with post mortem (PM) at 9 or 24 weeks, early exercise training (from 5-9 weeks of age) with PM at 9 or 24 weeks, or later exercise training (from 20-24 weeks of age) with PM at 24 weeks (n=8 males/group). Exercise training involved treadmill running 5 days/ week for 4 weeks. Running duration progressively increased from 20 up to 60 minutes per day, with the treadmill speed set at 15 m/min for the first week and 20 m/min thereafter. At 9 or 24 weeks of age rats were killed with an intraperitoneal injection of Ilium Xylazil-20 (30 mg/kg) and Ketamine (225 mg/kg). The rats in the 9 week old early exercise and 24 week old later exercise groups were killed 72 hours following the last bout of treadmill running. Total RNA was obtained from the whole-hearts for analysis
Project description:Transcriptomic profiles could help understand the prenatal mortality after selection for ovulation rate. This study aims to perform the gene expression pattern in ovarian tissue using microarrays from females belonging to the selected line and control line. Our results showed genes which could explain a high ovulation rate associated with lower prenatal survival in selected line females.