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Early-onset acute myocardial infarction (AMI) may have a higher genetic predisposition than late-onset AMI does. The present study aimed to identify and characterize germline variants that affect early-onset AMI using whole-genome sequencing (WGS). We performed a genome-wide association study based on WGS of 1,239 Koreans, including 596 early-onset AMI patients and 643 healthy individuals. Patients with AMI who underwent percutaneous coronary intervention (PCI) caused by atherothrombotic occlusive lesions were included in the study. A total of 29 novel loci were found to be associated with early-onset AMI. These loci are involved in thrombosis, fibrinolysis, inflammation, and lipid metabolism. One of the associated single nucleotide variants (SNVs), rs1614576, located upstream of PRKCB, is known to be associated with thrombus formation. Additionally, the results revealed a novel locus, rs78631167, located upstream of PLAUR which plays a critical role in regulating plasminogen activation and is related to fibrinolysis. The association between early-onset AMI and rs9357455, which is located upstream of PHACTR1 that regulates inflammation in AMI, was found. Moreover, we could identify a lipid metabolism related genetic risk locus, rs5072, in the APOA1-AS gene. This study provides new evidence supporting the genetic association between early-onset AMI and thrombosis and fibrinolysis, as well as inflammation and lipid metabolism, by analyzing the whole-genome of 596 patients with early-onset AMI who have been treated with PCI. Our findings highlight potential genetic markers for the prediction and management of AMI, as well as for understanding the etiology of AMI.

1,2-Diacetylbenzene (DAB) is a metabolite of 1,2-diethylbenzene, which is commonly used in the manufacture of plastics and gasoline. We examined the neurotoxic effects of DAB in young and old rats, particularly its effects on hippocampus. Previously, we reported DAB impairs hippocampal neurogenesis but that the underlying mechanism remained unclear. In this study, we evaluate the toxicities exhibited by DAB in the hippocampi of 6-month-old (young) and 20-month-old (old) male SD rats by treating animals intraperitoneally with DAB at 3 mg/kg/day for 1 week. Hippocampal areas were dissected from brains and RNA was extracted and subjected to RNA-seq analysis. RNA results showed animals exhibited age-dependent sensitivity to the neurotoxic effects of DAB. We observed that inflammatory pathways were up-regulated in old rats but that metabolism- and detoxification-related pathways were up-regulated in young rats. This result in old rats, especially upregulation of the TREM1 signaling pathway (an inflammatory response involved in Alzheimer's disease (AD)) was confirmed by RT-PCR. Our study results provide a better understanding of age-dependent responses to DAB and new insight into the association between DAB and AD.

The Korea Research Institute of Standards and Science (KRISS) established a new standard of the absorbed dose to water in LINAC X-ray beams. To confirm the equivalence of the new standard with other national metrology institutes (NMIs), a bilateral comparison study of the absorbed dose to water in high energy X-ray beams was performed between the KRISS and the National Metrology Institute of Japan (NMIJ). The comparison was made in-directly. Three transfer chambers were calibrated in the high energy X-ray beams by both laboratories and the calibration coefficients were compared. The average ratios of the calibration coefficients of the three transfer chambers obtained by the KRISS to those obtained by the NMIJ were 1.004, 1.006, 1.006, 1.007 for 6, 10, 15 and 18 MV X-ray beams, respectively. The calibration coefficients obtained at the KRISS were higher than those at the NMIJ but they were in good agreement within the expanded uncertainty of 1.0% (k = 2). The results of this study will be used as the evidence for the KRISS standard being comparable with those of other NMIs, temporarily, in the interim period up to finalizing a key comparison study, BIPM.RI(I)–K6 managed by the Consultative Committee for Ionizing Radiation.

Radiotherapy for cancer patients requires accurate measurement of the absorbed dose of radiation in a treatment planning step. Various types of radiation detectors are currently utilized for dose measurement. Among them, calorimeters are known to be the most precise detector for measuring absorbed dose, but their on-site application is limited by the large size of the equipment. We developed a miniaturized chip calorimeter for application as a radiation detector. The calorimetric radiation detector was built using micro/nano fabrication techniques, and consists of an SU-8 photoresist absorber and high-sensitivity vanadium oxide (VOx) thermistors. The thermistors had a temperature resolution of 135 μK, and the calorimeter showed a thermal conductance of 11 μW/K. The detector was irradiated with various X-ray dose rates from a linear accelerator, and the absorbed dose to SU-8 was measured. The detector responses showed high linearity with dose rates, demonstrating the feasibility of the radiation detector for practical uses.

Early detection is critical for minimizing mortality from cancer. Plasma cell-free DNA (cfDNA) contains the signatures of tumor DNA, allowing us to quantify the signature and diagnose early-stage tumors. Here, we report a novel tumor fragment quantification method, TOF (Tumor Originated Fragment) for the diagnosis of lung cancer by quantifying and analyzing both the plasma cfDNA methylation patterns and fragmentomic signatures. TOF utilizes the amount of ctDNA predicted from the methylation density information of each cfDNA read mapped on 6243 lung-tumor-specific CpG markers. The 6243 tumor-specific markers were derived from lung tumor tissues by comparing them with corresponding normal tissues and healthy blood from public methylation data. TOF also utilizes two cfDNA fragmentomic signatures: 1) the short fragment ratio, and 2) the 5' end-motif profile. We used 298 plasma samples to analyze cfDNA signatures using enzymatic methyl-sequencing data from 201 lung cancer patients and 97 healthy controls. The TOF score showed 0.98 of the area under the curve in correctly classifying lung cancer from normal samples. The TOF score resolution was high enough to clearly differentiate even the early-stage non-small cell lung cancer patients from the healthy controls. The same was true for small cell lung cancer patients.

This study was supported by the Basic Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT, Korea (Grant number NRF-2016R1A2B4007452).

Purpose The complex beam delivery techniques for patient treatment using a clinical linear accelerator (linac) may result in variations in the photon spectra, which can lead to dosimetric differences in patients that cannot be accounted for by current treatment planning systems (TPSs). Therefore, precise knowledge of the fluence and energy spectrum (ES) of the therapeutic beam is very important. However, owing to the high energy and flux of the beam, the ES cannot be measured directly, and validation of the spectrum modeled in the TPS is difficult. The aim of this study is to develop an efficient beam transmission measurement procedure for accurately reconstructing the ES of a therapeutic x-ray beam generated by a clinical linac. Methods The attenuation of a 6 MV photon beam from an Elekta Synergy Platform clinical linac through different thicknesses of graphite and lead was measured using an ion chamber. The response of the ion chamber as a function of photon energy was obtained using the Monte Carlo (MC) method in the Geant4 simulation code. Using the curves obtained in the photon beam transmission measurements and the ion chamber energy response, the ES was reconstructed using an iterative algorithm based on a mathematical model of the spectrum. To evaluate the accuracy of the spectrum reconstruction method, the reconstructed ES (ESrecon ) was compared to that determined by the MC simulation (ESMC ). Results The ion chamber model in the Geant4 simulation was well validated by comparing the ion chamber perturbation factors determined by the TRS-398 calibration protocol and EGSnrc; the differences were within 0.57%. The number of transmission measurements was optimized to 10 for efficient spectrum reconstruction according to the rate of increase in the spectrum reconstruction accuracy. The distribution of ESrecon obtained using the measured transmission curves was clearly similar to the reference, ESMC , and the dose distributions in water calculated using ESrecon and ESMC were similar within a 2% local difference. However, in a heterogeneous medium, the dose discrepancy between them was >5% when a complex beam delivery technique composed of 171 control points was used. Conclusions The proposed measurement procedure required a total time of approximately 1 h to obtain and analyze 20 transmission measurements. In addition, it was confirmed that the transmission curve of high-Z materials influences the accuracy of spectrum reconstruction more than that of low-Z materials. A well-designed transmission measurement protocol suitable for clinical environments could be an essential tool for better dosimetric accuracy in patient treatment and for periodic verification of the beam quality.

An isotropic pitch was electrospun in the form of a felt, by adopting a specially-designed dual concentric nozzle system. In the dual nozzle system, the solvent of tetrahydrofuran (THF) flowed independently through the outer nozzle, and relieved the problem of the too rapid coagulation of pitch fibers in the inner nozzle. Unlike the non-woven pitch fabric prepared by conventional electrospinning, the pitch felt had a characteristic morphology of fiber bundles, highly isolated from each other with few fusion points between fibers. The felt morphology was retained, during carbonization of the pitch felt. In consequence, the carbon felt took a sponge-like form, and showed extremely low bulk density of ca. 4.2×10−2 g/cm3, almost one tenth of that of the polyacrylonitrile-based carbon fibers in the form of non-woven fabric. The cross-section of the felt fibers exhibited the shape of a dog bone, due to asymmetric shrinkage of fibers during electrospinning. Physical properties of the felt were affected by pitch concentration, flow rate, and carbonization temperature.

Radiochromic films (RCFs) are widely used to check the dose distribution for quality assurance in radiation therapy . A flatbed scanner is the most common tool for RCFs. Analyzing RCFs with a flatbed scanner requires many considerations, including the energy correction for various beams, scanning orientation, film handling, film uniformity in a sheet or in a batch, scanning temperature, scanning software, and optical density to dose conversion. For RCFs to be a good tool for measuring the two-dimensional dose distribution, medical physicists should carefully follow a confirmed procedure to obtain the best dose distribution results. We focused on the absolute dose measurement at a point instead of the two-dimensional dose distribution and reduced human loads. A one-stop processing system from film readings to the dose evaluation was developed using a spectrometer, a light emitting diode (LED), and a film changer. Our system is characterized by the flexibility of selective light sources for RCFs and the ability to analyze absorbance spectra. EBT3 film was selected for this study, and our system was constructed to fit RCFs. The performance of the system was tested, and the evaluated dose was compared with a scanner. The irradiated dose and evaluated dose showed good agreement, within 3.2% deviation.

The solution of poly(2-cyano-p-phenylene terephthalamide) (CY-PPTA) in N,N-dimethyl acetamide/lithium chloride exhibited a concentration-dependent transition of liquid crystalline textures from nematic-rich to cholesteric-rich with increasing concentration above the critical concentration. The 2D correlation analysis of the FTIR spectra revealed that the dipolar interactions between cyano groups of the polymer increased as concentration increased. The polarized cyano group withdrew the delocalized π-electrons in the C-N bond of the amide group of the polymer, increasing its single bond character. The molecular simulation based on this spectroscopic evidence proposed a change of molecular shapes of CY-PPTA from linear rigid rod to semi-rigid helix. The semi-rigid helical conformation where the single bond character was prevalent over the delocalized one in the C-N bond would develop a cholesteric liquid crystalline texture.

In this study, we developed a semi-active method to run a graphite calorimeter in the quasi-isothermal mode under high-energy x-ray beams. The rate of energy imparted by the beam during irradiation was compensated mainly by removing the electrical heating power based on the pre-calculation and in part by an active automated algorithm, as well, while the temperature of the calorimeter core was kept constant. Irradiations were performed under the linear electron accelerator x-ray beams at 6, 8, 10, 15, and 18 MV. A simple model was applied to analyze the results. The energy imparted to the core was determined with an uncertainty level of 0.2%–0.3%, and the results were reaffirmed by comparing it with that obtained by the quasi-adiabatic mode. The normalized root-mean-square deviation to the mean from the quasi-adiabatic mode was 0.11%, and the associated uncertainty was 0.16% taking into account the correlation of the uncertainty components. This level of agreement showed that the present method is practical for the high-energy x-ray dosimetry.

Poly(1-oxotrimethylene) (POTM) was dissolved in aqueous solutions containing ZnCl2, CaCl2, and LiCl, and the effects of boric acid introduction on the phase stability of the POTM solutions over various aging times were investigated. In the absence of boric acid, aging at 70°C for 8 h notably reduced the loss tangent (tanδ) for the 7.0 wt.% POTM solutions. Addition of boric acid into unaged solutions had little effect on tanδ over the frequency range measured, regardless of its content, whereas addition of 0.3-1.0 wt.% of boric acid into aged solutions increased tanδ. The dynamic viscosity of the POTM solutions with 1.0 wt.% boric acid was affected little by aging time. Conversely, the POTM solutions without boric acid exhibited increased dynamic viscosity in the low-frequency range with aging time. In addition, the slope of the solutions in the Cole-Cole plot decreased with increasing aging time in the absence of boric acid, whereas aging time had little effect in the presence of 1.0 wt.% boric acid. For dilute POTM solutions (i.e., 0.5 g/dL), the reduced viscosity decreased with increasing aging time in the absence of boric acid, while it was affected little in solutions with the addition of 1.0 wt.% boric acid. In the UV-Vis spectra, the aging-time-dependent increase of the absorbance peak at 390 nm was associated with the generation of a chromophoric complex in the POTM solutions. Conversely, the disappearance of the peak due to the addition of boric acid indicated suppression of complex formation.

High-energy ionizing radiation therapy is a highly effective method for destroying cancer cells. Monitoring the dose distribution during radiation therapy is extremely important to deliver an optimal X-ray dose to diseased areas and minimize radiation exposure to adjacent healthy tissues. Here, we present an X-ray acoustic (XA) dosimetry system that successfully combines a spherically focused ultrasound (US) transducer with a medical linear accelerator. The system can be potentially utilized in clinical radiation therapy as an intratherapy dosimetry tool. The measured XA signal showed good correlation with the water-absorbed dose measured with conventional dosimetry. We acquired the absorbed X-ray dose distribution in a lead sample by mechanically scanning the focused US transducer. The lateral spatial resolution of the XA signal was 2.1 ± 0.5 mm, and signal-to-noise ratio of the signal was maintained with 100-mm penetration depth, whereas that of a laser-driven photoacoustic signal was exponentially decreased.

Most inorganic nucleating agents for poly(ethylene terephthalate) (PET) have limited nucleating ability due to poor compatibility with PET. Polyhedral oligomeric silsesquioxanes (POSS) is a type of cage-shaped organic/inorganic hybrid nanoparticles with three different particle sizes: octameric (T8), decameric (T10), and dodecameric (T12). POSS is considered as a promising nucleating agent for PET because the inorganic moieties contribute to high thermal stability and nucleation and the organic moieties can be tethered to PET chains. In contrast to T8 POSS, the nucleation ability of T12 POSS for PET has been poorly reported. In this study, our newly synthesized aminopropyl functionalized T12 POSS (A-POSS) is proposed as a potential nucleating agent for PET. The amine group of A-POSS is able to be chemically conjugated to PET chains, thereby giving a more homogeneous dispersion of T12 POSS in PET than non-functional T12 Phenyl POSS (N-POSS). Its PET composites gave a ∼1.2 fold higher crystallization temperature and ∼2.7 fold higher shear-induced crystallization rate over pristine PET. Such nucleating effects for PET is more effective than those of non-functional T12 POSS and the more widely studied T8 POSS. This strategy is potentially beneficial for the high-shear melt processes of PET such as spinning and film extrusion.

A graphite calorimetry system was built and tested under irradiation. The noise level of the temperature measurement system was approximately 0.08 mK (peak to peak). The temperature of the core part rose by approximately 8.6 mK at 800 MU (monitor unit) for 6-MV X-ray beams, and it increased as X-ray energy increased. The temperature rise showed less spread when it was normalized to the accumulated charge, as measured by an external monitoring chamber. The radiation energy absorbed by the core part was determined to have values of 0.798 J/μC, 0.389 J/μC, and 0.352 J/μC at 6 MV, 10 MV, and 18 MV, respectively. These values were so consistent among repeated runs that their coefficient of variance was less than 0.15%.

The molecular modification of polycaprolactone (PCL) is of great importance for producing optimum physical properties for a given application. Linear polycaprolactone (L-PCL) and 4-arm star polycaprolactone (4-PCL) with similar molecular weights were prepared, and their rheological, thermal, and morphological properties were investigated in relation to their molecular architecture. In dilute solutions, L-PCL exhibited a higher intrinsic viscosity than 4-PCL. In the molten state, the former displayed a higher viscosity and greater temperature dependence of molecular relaxation time than the latter. DSC thermograms showed that molecular architecture had little effect on the melting/crystallization temperature and crystallinity. Thermogravimetric analysis indicated that the introduction of a branched structure deteriorated the thermal stability of PCL, which might be associated with the increased number of hydroxyl end groups in the polymer chains. In isothermal crystallization under shear at two different temperatures, 4-PCL exhibited longer crystallization times than L-PCL. A more notable difference in dynamic crystallization behavior caused by the chemical architecture was observed at 40°C than at 45°C. Examination with a wide angle X-ray diffractometer revealed that shear and temperature applied during isothermal crystallization, as well as chemical architecture, had little effect on the crystal structure.

The physical properties and gelation behavior of polyacrylonitrile (PAN) solutions were investigated in mixed solvents of N,N-dimethyl formamide (DMF) and dimethyl sulfoxide (DMSO). In the individual solubility parameters, DMSO had the polar term closer to PAN than DMF. The SAXS profiles and FT-IR spectra of 20 wt% PAN solutions confirmed that internal structure and intermolecular complex between nitrile groups were broken up by the DMSO molecules. The slope on Cole-Cole plot, a measure of the solution heterogeneity, was increased with the mole fraction of DMSO (XDMSO) via three distinct zones. The homogenization was particularly noticeable in Zone 1 (0.0 < XDMSO < 0.4) and Zone 3 (0.7 < XDMSO < 1.0). The Huggins constant and UV/vis absorbance at 268 nm of dilute solutions decreased sharply above the XDMSO of 0.7 in Zone 3. This indicated the marked increase of the PAN solubility by dissociating the intramolecular complex between nitrile groups. In Zone 1, the storage modulus of 20 wt% PAN solutions decreased but loss modulus remained almost constant with the XDMSO at the lower frequency below 1 rad/s, indicating the weakening of the true entanglement points possessing the intermolecular complexes. The mechanism represented that the intermolecular complexes between nitrile groups were dissociated by DMSO earlier than the intramolecular ones.

The dipole-dipole interactions between polar nitrile groups of polyacrylonitrile (PAN) affected the molecular weight distribution (MWD)-dependent viscosity behavior of the solutions in N,N-dimethyl formamide (DMF) and dimethyl sulfoxide (DMSO). In both solvents, the 16 wt% PAN solutions of broader MWD but same weight average molecular weight (MWw) of 150,000 showed more prominent shear-thinning behavior, agreeing qualitatively with the theoretical prediction by Middleman. The dependence of the thinning behavior on the MWD was more pronounced with DMSO. The decrease of the power-law index by broadening of the MWD was more noticeable in DMSO than in DMF. The UV/vis and FTIR spectra confirmed that DMF produced stronger intra- and intermolecular dipole-dipole pairs between nitrile groups of PAN than DMSO. This indicated that physical association between polymer molecules limited the internal plasticizing effect of the low MWw molecules by disturbing the chain interdiffusion and shear-induced disentanglement. Over the whole range of frequency measured, the higher content of the higher MWw molecules in the broader MWD solutions resulted in the increase of dynamic viscosity and relaxation time but decrease of loss tangent.

The initial phase of the Korean Genome Project (Korea1K) releases 1094 whole genomes, along with data of 79 clinical traits., We present the initial phase of the Korean Genome Project (Korea1K), including 1094 whole genomes (sequenced at an average depth of 31×), along with data of 79 quantitative clinical traits. We identified 39 million single-nucleotide variants and indels of which half were singleton or doubleton and detected Korean-specific patterns based on several types of genomic variations. A genome-wide association study illustrated the power of whole-genome sequences for analyzing clinical traits, identifying nine more significant candidate alleles than previously reported from the same linkage disequilibrium blocks. Also, Korea1K, as a reference, showed better imputation accuracy for Koreans than the 1KGP panel. As proof of utility, germline variants in cancer samples could be filtered out more effectively when the Korea1K variome was used as a panel of normals compared to non-Korean variome sets. Overall, this study shows that Korea1K can be a useful genotypic and phenotypic resource for clinical and ethnogenetic studies.

Effects of chain conformation of polyacrylonitrile (PAN) on the aging behavior of the solutions in N , N -dimethyl formamide (DMF) were investigated over the range of aging temperature from 30 to 100 °C. Aging of PAN solutions reduced the hydrodynamic diameter and inherent viscosity at 0.5 g/dl. The absorption peak at 268 nm in the UV–vis spectra represented the dipole-dipole pairs of the physically associated nitrile (CN) groups, whose intensity increased with aging temperature above 60 °C. The results confirmed that aging of the solutions produced the contracted chain conformation with predominantly anti-parallel orientation of CN groups. Analyses of the temperature-dependent FTIR spectra and its two-dimensional correlation spectroscopy evidenced that thermal-induced conformational change of PAN to the contracted structure directly induced the reorientation of CN groups and resultant dipole-dipole pairs in the 70–100 °C range. In addition, the aging caused the release of the bound DMF molecules from CN groups. In the 30–60 °C range, however, the conformational change to the extended structure was followed by the increase of solvent entropy and resultant dissociation of solvent aggregates. Then, highly diffused DMF molecules separated the partially dissociated CN groups.

The viscoelastic properties of polyacrylonitrile (PAN) gels prepared from the 20 wt% solutions in N,N-dimethyl formamide (DMF) were investigated under large amplitude oscillatory shear (LAOS) in terms of aging temperature of the solutions from 30 to 100 °C. Aging of PAN solutions reduced intrinsic viscosity and hydrodynamic diameter with little degradation. In the UV–vis spectra, the absorption peak at 268 nm represented the dipole-dipole pairs of physically associated nitrile groups, whose intensity increased with aging temperature. These results confirmed that aging of the solutions gave rise to the contracted chain conformation with anti-parallel orientation-dominant nitrile groups. In 20 wt%, aged solutions showed gelation behavior more rapid than fresh one during storage at 25 °C. At the imposed strain amplitude of 400% in the LAOS measurement, PAN gel prepared from fresh solution gave sinusoidal waveform signal of stress and ellipse-shape Lissajous curve. However, gels from the solutions aged above 60 °C showed non-sinusoidal stress waveform and characteristic Lissajous pattern, representing strain-stiffening behavior. In addition, the gel of the solution aged at 100 °C gave the greater strain-stiffening ratio than the initial value after the successive LAOS tests at 80 and 30 °C, indicating the thermo-irreversibility.

In this study, efforts were made to enhance the mechanical properties of the poly(vinyl alcohol) (PVA) fibers of medium molecular weight(number-average degree of polymerization=1735) varying the ratio in DMSO/H2O mixed solvent and spinning/drawing conditions. The gel fibers prepared from pure DMSO were opaquely frozen in the coagulating bath of -20℃. However, transparent gel fibers were formed without freezing for the mixture to contain water less than 80wt%. As the amount of water in the mixture increased the residual solvent in the coagulated gel fibers decreased ranging from 85 to 42wt%. The complex viscosity increased with increasing PVA concentration in 80/20 DMSO/H2O exhibiting remarkable shear thinning at 18wt%. In the Cole-Cole plot, the 18wt% PVA solutions gave a deviated curve from 12 and 15wt% ones. Thus the optimum PVA concentration for the spinning processing of medium MW PVA solutions in 80/20 DMSO/H2O was determined to 18wt% with rheological concept. Low degree of drawing during hot drawing process in the dry state was available for high bath draft in the coagulation bath. The most improved mechanical properties were observed by applying the highest possible draw ratio attained by reducing bath draft over multi-step drawing process. In the given bath draft, linear relationship was observed between both tensile strength and modulus and draw ratio showing the inflection points at the draw ratio of 19.5 and 18.0 for tensile strength and modulus, respectively.

Summary DNA methylation plays major roles in many biological processes, including aging, carcinogenesis, and development. Analyses of DNA methylation using next-generation sequencing offer a new way to profile and compare methylomes across the genome in the context of aging. We explored genomewide DNA methylation and the effects of short-term calorie restriction (CR) on the methylome of aged rat kidney. Whole-genome methylation of kidney in young (6 months old), old (25 months old), and OCR (old with 4-week, short-term CR) rats was analyzed by methylated DNA immunoprecipitation and next-generation sequencing (MeDIP-Seq). CpG islands and repetitive regions were hypomethylated, but 5′-UTR, exon, and 3′-UTR hypermethylated in old and OCR rats. The methylation in the promoter and intron regions was decreased in old rats, but increased in OCR rats. Pathway enrichment analysis showed that the hypermethylated promoters in old rats were associated with degenerative phenotypes such as cancer and diabetes. The hypomethylated promoters in old rats related significantly to the chemokine signaling pathway. However, the pathways significantly enriched in old rats were not observed from the differentially methylated promoters in OCR rats. Thus, these findings suggest that short-term CR could partially ameliorate age-related methylation changes in promoters in old rats. From the epigenomic data, we propose that the hypermethylation found in the promoter regions of disease-related genes during aging may indicate increases in susceptibility to age-related diseases. Therefore, the CR-induced epigenetic changes that ameliorate age-dependent aberrant methylation may be important to CR's health- and life-prolonging effects.