Search bioRxiv⌕ Search

Biology subjects

Carreras-Gallo, N.

Publications and source records attributed to Carreras-Gallo, N..

3 recordsLinked to original sources

The Impact of a Natural Ingredients based Intervention Targeting the Nine Hallmarks of Aging on DNA methylation

Aging interventions have progressed in recent years due to the growing curiosity about how lifestyle impacts longevity. This study assessed the effects of SRW Laboratories Cel System nutraceutical range on epigenetic methylation patterns, inflammation, physical performance, body composition, and epigenetic biomarkers of aging. A 1-year study was conducted with 51 individuals, collecting data at baseline, 3 months, 6 months, and 12 months. Participants were encouraged to walk 10 minutes and practice 5 minutes of mindfulness daily. Significant improvements in muscle strength, body function, and body composition metrics were observed. Epigenetic clock analysis showed a decrease in biological age with significant reductions in stem cell division rates. Immune cell subset analysis indicated significant changes, with increases in eosinophils and CD8T cells and decreases in B memory, CD4T memory, and T-regulatory cells. Predicted epigenetic biomarker proxies (EBPs) showed significant changes in retinol/TTHY, a regulator of cell growth, proliferation, and differentiation, and deoxycholic acid glucuronide levels, a metabolite of deoxycholic acid generated in the liver. Gene ontology analysis revealed significant CpG methylation changes in genes involved in critical biological processes related to aging, such as oxidative stress-induced premature senescence, pyrimidine deoxyribonucleotide metabolic process, TRAIL binding, hyaluronan biosynthetic process, neurotransmitter loading into synaptic vesicles, pore complex assembly, collagen biosynthetic process, protein phosphatase 2A binding activity, and activation of transcription factor binding. Our findings suggest that the Cel System supplement range may effectively reduce biological age and improve health metrics, warranting further investigation into its mechanistic pathways and long-term efficacy.

genomics↗

Creation and Validation of the First Infinium DNA Methylation Array for the Human Imprintome

BackgroundDifferentially methylated imprint control regions (ICRs) regulate the monoallelic expression of imprinted genes. Their epigenetic dysregulation by environmental exposures throughout life results in the formation of common chronic diseases. Unfortunately, existing Infinium methylation arrays lack the ability to profile these regions adequately. Whole genome bisulfite sequencing (WGBS) is the unique method able to profile these regions, but it is very expensive and it requires not only a high coverage but it is also computationally intensive to assess those regions. FindingsTo address this deficiency, we developed a custom methylation array containing 22,819 probes. Among them, 9,757 probes map to 1,088 out of the 1,488 candidate ICRs recently described. To assess the performance of the array, we created matched samples processed with the Human Imprintome array and WGBS, which is the current standard method for assessing the methylation of the Human Imprintome. We compared the methylation levels from the shared CpG sites and obtained a mean R2 = 0.569. We also created matched samples processed with the Human Imprintome array and the Infinium Methylation EPIC v2 array and obtained a mean R2 = 0.796. Furthermore, replication experiments demonstrated high reliability (ICC: 0.799-0.945). ConclusionsOur custom array will be useful for replicable and accurate assessment, mechanistic insight, and targeted investigation of ICRs. This tool should accelerate the discovery of ICRs associated with a wide range of diseases and exposures, and advance our understanding of genomic imprinting and its relevance in development and disease formation throughout the life course.

genetics↗

OMICmAge: An integrative multi-omics approach to quantify biological age with electronic medical records

Biological aging is a multifactorial process involving complex interactions of cellular and biochemical processes that is reflected in omic profiles. Using common clinical laboratory measures in ~30,000 individuals from the MGB-Biobank, we developed a robust, predictive biological aging phenotype, EMRAge, that balances clinical biomarkers with overall mortality risk and can be broadly recapitulated across EMRs. We then applied elastic-net regression to model EMRAge with DNA-methylation (DNAm) and multiple omics, generating DNAmEMRAge and OMICmAge, respectively. Both biomarkers demonstrated strong associations with chronic diseases and mortality that outperform current biomarkers across our discovery (MGB-ABC, n=3,451) and validation (TruDiagnostic, n=12,666) cohorts. Through the use of epigenetic biomarker proxies, OMICmAge has the unique advantage of expanding the predictive search space to include epigenomic, proteomic, metabolomic, and clinical data while distilling this in a measure with DNAm alone, providing opportunities to identify clinically-relevant interconnections central to the aging process.

bioinformatics↗