Individuals experiencing Werner syndrome (WS) show many clinical indications of accelerated

Individuals experiencing Werner syndrome (WS) show many clinical indications of accelerated aging. blood cell composition. The degree to which this alteration is definitely a cause or effect of WS 6902-91-6 manufacture disease phenotypes remains unfamiliar. gene, which encodes a 1432 amino acid protein having a central website characteristic of users of the Rec Q family of helicases. The medical phenotype 6902-91-6 manufacture of WS includes scleroderma-like skin changes, bilateral ocular cataracts, type 2 diabetes mellitus, osteoporosis, hypogonadism, and atherosclerosis. The most common causes of death are malignancy and myocardial infarction and the average age at death is definitely 54 years [1, 2]. Little is known about the association of epigenetic alterations with WS. Several recent studies have proposed to measure the physiological age of tissue samples by combining the DNA methylation levels of multiple dinucleotide markers, known as Cytosine phosphate Guanines or CpGs [3-7]. In particular, the Epigenetic Clock was developed to measure the age of sorted human being cell types (CD4+ T 6902-91-6 manufacture 6902-91-6 manufacture cells or neurons), all cells, and organs including blood, brain, breast, kidney, liver, and lung [6]. The epigenetic clock is definitely defined as a weighted average across 353 CpG sites. The producing age estimate (in devices of years) is referred to as “DNA methylation age” (DNAm age) or “epigenetic age”. Recent studies support the idea that epigenetic age estimations are at least passive biomarkers of biological age. For instance, the epigenetic age of NPM1 blood has been found to be predictive of all-cause mortality [8-12], frailty [13], lung cancer [14], and cognitive and physical functioning [15]. Further, the utility of the epigenetic clock method using various tissues and organs has been demonstrated in studies of Alzheimer’s disease [16], centenarian status [10, 17], Down syndrome [18], HIV infection [19], Huntington’s disease [20], obesity [21], lifetime stress [22], menopause [23], osteoarthritis [24], and Parkinson’s disease [25]. Despite many diverse applications of the epigenetic clock, we are not aware of any studies that have analyzed epigenetic aging rates in WS. Here we show for the first time that measures of epigenetic age acceleration are indeed associated with WS status. Different from typical epigenome-wide association studies (EWAS) that interrogate individual CpGs, the current study posits a single hypothesis: WS is associated with epigenetic age acceleration in blood cells. In a secondary analysis, we also relate WS status to abundance measures of blood cell types that were estimated using DNA methylation data. RESULTS Subjects and tissue We analyzed DNA methylation levels by the Illumina Infinium MethylationEPIC BeadChip in whole blood of 18 patients with confirmed mutations in the gene (16 male, 2 female) and 18 controls, which were matched for age and for gender (with one exception: 15 male, 3 female) (Table ?(Table11). Table 1 Sample characteristics of matched WS cases and controls Accuracy of the epigenetic clock DNAm age (also referred to as epigenetic age) was calculated as described in [6]. Mathematical details and software tutorials for the epigenetic clock can be found in the Additional files of [6]. An online age calculator can be found at our webpage ( All of the described epigenetic measures of aging and age acceleration are implemented in our freely available software. As expected, DNAm age has a strong linear relationship with chronological age (r=0.83, Figure ?Figure1A1A). Figure 1 Epigenetic age analysis of Werner syndrome Werner syndrome is associated with intrinsic and extrinsic epigenetic age acceleration In this article, we consider three measures of epigenetic age acceleration (Methods). The first measure, which will be referred to as a universal measure of age acceleration (denoted AgeAccel) applies to virtually all tissues and cell types (with the exception of sperm). The other two.