Project description:Osteoporosis is an age-related metabolic bone disease. Hence, osteoporotic patients might suffer from molecular features of accelerated aging, which is generally reflected by specific age-associated DNA methylation (DNAm) changes. In this study, we analyzed genome wide DNAm profiles of peripheral blood from patients with manifest primary osteoporosis and non-osteoporotic controls. Statistical analysis did not reveal any individual CG dinucleotides (CpG sites) with significant aberrant DNAm in osteoporosis. Subsequently, we analyzed if age-associated DNAm patterns are increased in OP. Using three independent age-predictors we did not find any evidence for accelerated epigenetic age in blood of osteoporotic patients. Taken together, osteoporosis is not reflected by characteristic DNAm patterns of peripheral blood that might be used as biomarker for the disease. The prevalence of osteoporosis is age-associated – but it is not associated with premature epigenetic aging in peripheral blood.
Project description:Epigenetic clocks can quantify DNA methylation by measuring the methylation levels at specific sites in the genome, which correlate with biological age (BA). Accelerated aging, where BA exceeds chronological age (CA), has been studied in relation to cancer development, but its utility in cancer prevention remains unclear. Accelerated aging holds promise as a tool to explain the rise in early onset colorectal cancer (EOCRC). We investigate the association of accelerated aging and the presence of pre-neoplastic polyps (PNP) in the colon, defined as tubular adenomas and sessile serrated adenomas. In this study of persons under age 50 undergoing colonoscopy, we used peripheral blood samples to determine BA and age acceleration metrics. Age acceleration was determined by interrogating DNA methylation (DNAm) at specific CpG sites across the genome, which has been shown to correlate with age. We then conducted logistic regression analyses to evaluate the association between age acceleration and PNPs. In total, 51 patient samples were evaluated. We found that that the odds of harboring a PNP are 17% higher with 1 year of accelerated aging, as measured by GrimAge. However, the strongest risk factor for PNPs remained male sex. This represents one of the first studies to explore accelerated aging and PNP in patients under the age of 50. A risk-stratified approach to EOCRC screening would minimize unnecessary colonoscopies and minimize healthcare burden while addressing the rise in EOCRC. Our findings suggest that BA calculations with peripheral blood collections could be an important component of such a risk model.
Project description:We evaluated biological aging using five epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge and DunedinPoAm) calculated from DNA methylation measured in peripheral blood cells in a trans-diagnostic psychiatric sample including healthy controls. We found that burden of psychiatric disease, represented by a weighted score, was significantly associated with biological age acceleration as measured by GrimAge and DunedinPoAm. The faster pace of aging was even further accelerated in individuals exposed to physical abuse in childhood
Project description:The main goal of the study was to measure the epigenetic age (also known as DNA methylation age) of human bone tissue and to relate it to chronological age. Toward this end, we used the epigenetic clock software described in Horvath S (2013) DNA methylation age of human tissues and cell types. Genome Biology.2013, 14:R115. DOI: 10.1186/10.1186/gb-2013-14-10-r115 PMID: 24138928 Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 486,000 CpGs. The trabecular bone pieces were obtained from the central part of the femoral head of Spanish (Caucasian) patients with hip fractures (due to osteoporosis) or subjects with osteoarthritis. About 85% of the cell population in this bone tissue are osteocytes and the remainder are osteoblasts, bone marrow, etc.
Project description:To determine if disease can modify aging patterns in an affected tissue without altering the aging patterns of other tissues, blood and semen of individuals with oligozoospermia (n=10) were compared to the blood and semen of individuals with normozoospermia (n=24). The Horvath and Jenkins age calculators were utilized to predict the epigenetic age of blood and sperm through the use of DNA methylation. Using these calculators, it was found that sperm of oligozoospermic men were predicted to be significantly older than the sperm of normozoospermic men; however, there was not a significant epigenetic age difference in blood. These results lead to the conclusion that tissue specific aging is occurring in sperm of oligozoospermic individuals but not in unaffected somatic tissues (in our case, blood).
Project description:Human DNA methylation Beadchip v1.2 was used to profile 508 whole blood samples. The main goal of the study was to relate Parkinson's disease status to measures of epigenetic age acceleration based on DNA methylation data. Here we focus on Caucasian subjects. To measure DNA methylation age, we used the epigenetic clock software described in Horvath S (n=2013) DNA methylation age of human tissues and cell types. Genome Biology.2013, 14:R115. DOI: 10.1186/10.1186/gb-2013-14-10-r115 PMID: 24138928.
Project description:Cannabis use has been controversial, largely having been designated a controlled substance over the last century. The link between cannabis smoking and disease pathogenesis may best be explored through DNA methylation, an epigentic mechanism. We investigated the relationship between epigenetic age and cannabis smoking in participants within the Canadian Cohort of Obstructive Lung Disease (CanCOLD) cohort (n=93) (ClinicalTrials.gov identifier NCT00920348). Blood samples were profiled for DNA methylation using the Illumina MethylationEPIC BeadChipv1 at two separate laboratories and the blood epigenetic age of each sample was calculated using the Clock Foundation tool (https://dnamage.clockfoundation.org). An ANOVA was used to identify differences in the age acceleration residuals associated with cannabis smoking status (never, former, and current), adjusted for chronological age, sex, body mass index (BMI), batch, cigarette smoking status, and the first two principal components of blood cell proportions. Our observations indicated that current cannabis smoking and higher joint-years exposure are associated with epigenetic age acceleration; cessation, however, may help to normalize in part this age acceleration.
Project description:In this study, we investigated whether stroke patients who later developed cancer exhibited an accelerated epigenetic age compared to those who did not. A total of 648 stroke patients were followed for 15 years, during which 83 individuals were diagnosed with cancer. Biological age (B-age) was estimated from DNA methylation data derived from whole blood samples collected within 24 hours of stroke onset. These samples were analyzed using the 450K or EPIC Illumina Beadchip arrays. We employed several epigenetic clocks to calculate B-age, including the Hannum, Horvath, PhenoAge, ZhangBLUP, ZhangEN, and the mitotic epiTOC clocks. After adjusting for multiple testing, competing risks, and key confounders, we found that patients who developed cancer were biologically older, as measured by the Hannum clock. This repository provides the raw idat files and processed DNA methylation values.
Project description:Human DNA methylation Beadchip v1.2 was used to profile n=84 whole blood samples from Hispanics living in the USA. The main goal of the study was to relate Parkinson's disease status to measures of epigenetic age acceleration based on DNA methylation data. Here we focus on Hispanic subjects. To measure DNA methylation age, we used the epigenetic clock software described in Horvath S (n=2013) DNA methylation age of human tissues and cell types. Genome Biology.2013, 14:R115. DOI: 10.1186/10.1186/gb-2013-14-10-r115 PMID: 24138928.
Project description:Long noncoding RNAs (lncRNAs) have emerged as integral regulators of physiology and disease, but specific roles of lncRNAs in bone disease remain largely unknown. Here, we show that lnc-ob1 regulates osteoblast activity and bone formation in mice by upregulating the osteogenic transcription factor Osterix. Expression of lnc-ob1 is enriched in osteoblasts and upregulated during osteoblastogenesis. We demonstrate that osteoblast-specific knock-in of lnc-ob1 enhances bone formation and increases bone mass. Pharmacological overexpression of lnc-ob1 specifically in osteoblasts confers resistance to ovariectomy-induced osteoporosis in mice. In humans, expression of the homologue, lnc-OB1, decreases with age in osteoblasts of patients with osteoporosis. Mechanistically, lnc-ob1 upregulates the expression of Osterix in mouse and human osteoblasts, probably via inhibition of H3K27me3 methylation. Our data indicate that lnc-OB1 regulates bone formation and might be a drug target for the treatment of osteoporosis.