Analysis of the epigenetic clock in liver tissue from young and old mice of different strains (C57BL6/J, Hnf4a+/0, Cebpa+/0, and Ctcf +/0)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus (mouse)
SUBMITTER:
PROVIDER: S-BSST1329 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Human DNA-methylation data have been used to develop highly accurate biomarkers of aging ("epigenetic clocks"). Recent studies demonstrate that similar epigenetic clocks for mice (Mus Musculus) can be slowed by gold standard anti-aging interventions such as calorie restriction and growth hormone receptor knock-outs. Using DNA methylation data from previous publications with data collected in house for a total 1189 samples spanning 193,651 CpG sites, we developed 4 novel epigenetic clocks by choosing different regression models (elastic net- versus ridge regression) and by considering different sets of CpGs (all CpGs vs highly conserved CpGs). We demonstrate that accurate age estimators can be built on the basis of highly conserved CpGs. However, the most accurate clock results from applying elastic net regression to all CpGs. While the anti-aging effect of calorie restriction could be detected with all types of epigenetic clocks, only ridge regression based clocks replicated the finding of slow epigenetic aging effects in dwarf mice. Overall, this study demonstrates that there are trade-offs when it comes to epigenetic clocks in mice. Highly accurate clocks might not be optimal for detecting the beneficial effects of anti-aging interventions.
| S-EPMC6224226 | biostudies-literature
Project description:Cancer immunotherapy is one of the most promising and benign therapies against metastatic cancer. However, most cancer patients are old and elderly react less efficient to cancer vaccines than young adults, due to T cell unresponsiveness. Here we present data of cancer vaccination in young and old mice with metastatic breast cancer (4T1 model). We tested adaptive and innate immune responses to foreign antigens (Listeria-derived) and self-antigens (tumor-associated antigens (TAA)) and their contribution to elimination of metastases at young and old age. Three different protocols were tested with Listeria: a semi- and exclusive-therapeutic protocol both one-week apart, and an exclusive therapeutic protocol frequently administered. Adaptive and innate immune responses were measured by ELISPOT in correlation with efficacy in the 4T1 model. We found that Listeria induced immunogenic tumor cell death, resulting in CD8 T cell responses to multiple TAA expressed by the 4T1 tumors. Only exclusive therapeutic frequent immunizations were able to overcome immune suppression and to activate TAA- and Listeria-specific CD8 T cells, in correlation with a strong reduction in metastases at both ages. However, MHC class Ia antibodies showed inhibition of CD8 T cell responses to TAA at young but not at old age, and CD8 T cell depletions in vivo demonstrated that the T cells contributed to reduction in metastases at young age only. These results indicate that CD8 T cells activated by Listeria has an antitumor effect at young but not at old age, and that metastases at old age have been eliminated through different mechanism(s).
| S-EPMC5599096 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-11-29 | GSE120137 | GEO
Project description:Several age predictors based on DNA methylation, dubbed epigenetic clocks, have been created in recent years, with the vast majority based on regularized linear regression. This study explores the improvement in the performance and interpretation of epigenetic clocks using deep learning. First, we gathered 142 publicly available data sets from several human tissues to develop AltumAge, a neural network framework that is a highly accurate and precise age predictor. Compared to ElasticNet, AltumAge performs better for within-data set and cross-data set age prediction, being particularly more generalizable in older ages and new tissue types. We then used deep learning interpretation methods to learn which methylation sites contributed to the final model predictions. We observe that while most important CpG sites are linearly related to age, some highly-interacting CpG sites can influence the relevance of such relationships. Using chromatin annotations, we show that the CpG sites with the highest contribution to the model predictions were related to gene regulatory regions in the genome, including proximity to CTCF binding sites. We also found age-related KEGG pathways for genes containing these CpG sites. Lastly, we performed downstream analyses of AltumAge to explore its applicability and compare its age acceleration with Horvath’s 2013 model. We show that our neural network approach predicts higher age acceleration for tumors, for cells that exhibit age-related changes in vitro, such as immune and mitochondrial dysfunction, and for samples from patients with multiple sclerosis, type 2 diabetes, and HIV, among other conditions. Altogether, our neural network approach provides significant improvement and flexibility compared to current epigenetic clocks for both performance and model interpretability.
| S-EPMC9158789 | biostudies-literature
Project description:Aging of the peripheral nervous system (PNS) is associated with structural and functional changes that lead to a reduction in regenerative capacity and the development of age-related peripheral neuropathy. Myelin is a central component in maintaining physiological peripheral nerve function, and differences in myelin maintenance, degradation, formation and clearance have been suggested to contribute to age-related PNS changes. In addition, recent proteomic studies have elucidated the complex composition of the total myelin proteome in health and its changes in neuropathy models. However, changes in the myelin proteome of peripheral nerves during ageing have not been investigated. Hence, the aim of this proteomics experiment was to define proteome changes in isolated myelin fractions during ageing, by investigating myelin proteome profiles from young (nerves from 2-3 month old mice) and old (nerves from 18 months old mice) nerves.
2023-10-19 | PXD040719 | Pride
Project description:BackgroundPostoperative delirium is one of the most common postoperative complications in geriatric patients. Mini-mental state examination (MMSE) assesses cognitive function in patients and is associated with postoperative delirium. However, whether there is an age-dependent relationship between preoperative MMSE score and postoperative delirium remains unknown.MethodsWe therefore set out to investigate the association between preoperative MMSE score and postoperative delirium in young-old (≤80 year-old, 75.46±4.69 years, 27.0% male, n = 63) and old-old (>80 year-old, 84.51±3.46 years, 20.9% male, n = 67) participants, who had repairs of hip fractures under general anesthesia. The Confusion Assessment Method and Memorial Delirium Assessment Scale were administrated before surgery, and on the first, second and fourth days after surgery, to assess the incidence and severity of the delirium, respectively. A receiver operating characteristic curve analysis was used to calculate the optimal cutoff score of MMSE in predicting postoperative delirium.ResultsThirty-four (26.2%) of 130 patients (80.12±6.12 years, 23.8% male) developed postoperative delirium. Preoperative MMSE scores were negatively associated with higher incidences and greater severity of postoperative delirium. The optimal cutoff scores of MMSE associated with postoperative delirium for young-old and old-old participants were 18.4 and 21.4, with a sensitivity of 60% and 83.8%, and a specificity of 92.5% and 62.8%, respectively.ConclusionThe data demonstrated the optimal cutoff score of MMSE associated with postoperative delirium in young-old adults might be lower than that in old-old adults. Pending further investigation, these findings suggest that the association between preoperative MMSE score and postoperative delirium is age-dependent.
| S-EPMC4603675 | biostudies-literature
Project description:Human DNA-methylation data have been used to develop highly accurate biomarkers of aging ("epigenetic clocks"). Recent studies demonstrate that similar epigenetic clocks for mice (Mus Musculus) can be slowed by gold standard anti-aging interventions such as calorie restriction and growth hormone receptor knock-outs. Using DNA methylation data from previous publications with data collected in house for a total 1189 samples spanning 193,651 CpG sites, we developed 4 novel epigenetic clocks by choosing different regression models (elastic net- versus ridge regression) and by considering different sets of CpGs (all CpGs vs highly conserved CpGs). We demonstrate that accurate age estimators can be built on the basis of highly conserved CpGs. However, the most accurate clock results from applying elastic net regression to all CpGs. While the anti-aging effect of calorie restriction could be detected with all types of epigenetic clocks, only ridge regression based clocks replicated the finding of slow epigenetic aging effects in dwarf mice. Overall, this study demonstrates that there are trade-offs when it comes to epigenetic clocks in mice. Highly accurate clocks might not be optimal for detecting the beneficial effects of anti-aging interventions.
2018-11-29 | GSE120136 | GEO
Project description:Human DNA-methylation data have been used to develop highly accurate biomarkers of aging ("epigenetic clocks"). Recent studies demonstrate that similar epigenetic clocks for mice (Mus Musculus) can be slowed by gold standard anti-aging interventions such as calorie restriction and growth hormone receptor knock-outs. Using DNA methylation data from previous publications with data collected in house for a total 1189 samples spanning 193,651 CpG sites, we developed 4 novel epigenetic clocks by choosing different regression models (elastic net- versus ridge regression) and by considering different sets of CpGs (all CpGs vs highly conserved CpGs). We demonstrate that accurate age estimators can be built on the basis of highly conserved CpGs. However, the most accurate clock results from applying elastic net regression to all CpGs. While the anti-aging effect of calorie restriction could be detected with all types of epigenetic clocks, only ridge regression based clocks replicated the finding of slow epigenetic aging effects in dwarf mice. Overall, this study demonstrates that there are trade-offs when it comes to epigenetic clocks in mice. Highly accurate clocks might not be optimal for detecting the beneficial effects of anti-aging interventions.
2018-11-29 | GSE120132 | GEO
Project description:Here we examine the chromatin landscapes of HSCs from young (2 months) vs old (24 months) mice bone marrow.
2023-02-22 | GSE219032 | GEO
Project description:Aging is associated with an increased risk of frailty, disability, and mortality. Strategies to delay the degenerative changes associated with aging and frailty are particularly interesting. We treated old animals with small extracellular vesicles (sEVs) derived from adipose mesenchymal stem cells (ADSCs) of young animals, and we found an improvement in several parameters usually altered with aging, such as motor coordination, grip strength, fatigue resistance, fur regeneration, and renal function, as well as an important decrease in frailty. ADSC-sEVs induced proregenerative effects and a decrease in oxidative stress, inflammation, and senescence markers in muscle and kidney. Moreover, predicted epigenetic age was lower in tissues of old mice treated with ADSC-sEVs and their metabolome changed to a youth-like pattern. Last, we gained some insight into the microRNAs contained in sEVs that might be responsible for the observed effects. We propose that young sEV treatment can promote healthy aging.
| S-EPMC9581480 | biostudies-literature