Mechanism of Guigan Longmu Decoction in the Treatment of Arrhythmias Based on Network Pharmacology and Untargeted Metabolomics Assays.

BACKGROUND: Guigan longmu decoction (GGLM), a traditional Chinese medicine compound, has demonstrated efficacy in treating rapid arrhythmia clinically. Nevertheless, its mechanism of action remains elusive. This study aims to elucidate the molecular mechanism underlying the efficacy of GGLM in treating arrhythmia utilizing non-targeted metabolomics, widely-targeted metabolomics, and network pharmacology, subsequently validated through animal experiments. METHODS: Initially, network pharmacology analysis and widely-targeted metabolomics were performed on GGLM. Subsequent to that, rats were administered GGLM intervention, and nontargeted metabolomics assays were utilized to identify metabolites in rat plasma postadministration. The primary signaling pathways, core targets, and key active ingredients of GGLM influencing arrhythmia were identified. Additionally, to validate the therapeutic efficacy of GGLM on arrhythmia rat models, a rat model of rapid arrhythmia was induced via subcutaneous injection of isoproterenol, and alterations in pertinent pathogenic pathways and proteins in the rat model were assessed through qRT-PCR and Western blot following GGLM administration. RESULTS: The results of network pharmacology showed that 99 active ingredients in GGLM acted on 249 targets and 201 signaling pathways, which may be key to treating arrhythmia. Widelytargeted metabolic quantification analysis detected a total of 448 active ingredients in GGLM, while non-targeted metabolomics identified 279 different metabolites and 10 major metabolic pathways in rats. A comprehensive analysis of the above results revealed that the core key active ingredients of GGLM in treating arrhythmia include calycosin, licochalcone B, glabridin, naringenin, medicarpin, formononetin, quercetin, isoliquiritigenin, and resveratrol. These active ingredients mainly act on the relevant molecules and proteins upstream and downstream of the MAPK pathway to delay the onset of arrhythmia. Animal experimental results showed that the heart rate of rats in the model group increased significantly, and the mRNA and protein expression of p38, MAPK, JNK, ERK, NF-kb, IL-1ß, and IL-12 in myocardial tissue also increased significantly. However, after intervention with GGLM, the heart rate of rats in the drug group decreased significantly, while the mRNA and protein expression of p38 MAPK, JNK, ERK1, NF-kb, IL-1ß, and IL-12 in myocardial tissue decreased significantly. CONCLUSION: GGLM, as an adjunctive therapy in traditional Chinese medicine, exhibits favorable therapeutic efficacy against arrhythmia. This can be attributed to the abundant presence of bioactive compounds in the formulation, including verminin, glycyrrhizin B, glabridine, naringenin, ononin, quercetin, isorhamnetin, and kaempferol. The metabolites derived from these active ingredients have the potential to mitigate myocardial inflammation and decelerate heart rate by modulating the expression of proteins associated with the MAPK signaling pathway in vivo.

[Source Appointment and Assessment of Heavy Metal Pollution in Surface Dust in the Main District Bus Stops of Tianshui City].

In this study, a PMF model was used to identify the sources and pollution level of heavy metals in the surface dust of a bus station. On the basis of the traditional heavy metal pollution evaluation methods, the Hakanson toxicity response coefficient was used to modify the traditional weight. The matter-element extension theory was introduced to reflect the toxicological properties and hazard degree of the heavy metals, and the matter-element extension model was established to evaluate the pollution level of heavy metals in the surface dust of the study area. The results were compared with Igeo, PN, and RI. ① Except for Co and V, the other heavy metals were higher than the Gansu soil background values by 1.29-9.30 times. The points of Cu and Pb exceeded the rate by 100%, and Cr, Ni, and As exceeded the rate by 96.15%, 94.23%, and 96.15%, respectively. ② PMF showed that source 1 was a natural source, and its contribution rate to V was 32.12%. Source 2 was natural-traffic pollution sources, contributing 51.50% and 33.37% to Cu and Co, respectively. Source 3 was a construction waste pollution source, with contribution rates of 45.06% and 44.70% for Cr and Ni, respectively, and source 4 was a coal-traffic mixed source, with contribution rates of 49.89% and 75.25% for As and Pb, respectively. ③ The matter-element evaluation results showed that the surface dust of the bus stops was mainly class IV (moderately polluted), and 13% of sample points were still clean, 37% were moderately polluted, and 25% were slightly and heavily polluted. The results of this method were quite different from the PN results and were more consistent with the RI results, indicating that its evaluation results were more sensitive and can be used for heavy metal pollution assessment.

A short review of the electrochemical technologies for pit arrays fabricated on the surfaces of indium phosphide wafer.

Fabricating a pit array on the surface of indium phosphide wafer can change its photoelectric properties, improve its photoelectric conversion efficiency, and expand its application range. There are few reviews devoted to the fabrication of regular hole arrays on the surface of indium phosphide wafers by electrochemical methods. In this paper, twelve electrochemical approaches for assembling pit arrays on the surface of indium phosphide wafers were introduced, the structure and experimental process of the electrochemical device were highlighted, and the resulting top and section views were also shown by animation. It can provide a useful reference guide for the large-scale fabrication of regular hole arrays on the surface of indium phosphide wafers.

Synergistic Effects of La and Y on the Microstructure and Mechanical Properties of Cast Al-Si-Cu Alloys.

The effects of La and Y on the microstructure and mechanical properties of cast Al-Si-Cu alloys were investigated by X-ray diffractometer (XRD), optical microscope (OM), and scanning electron microscope (SEM). The results indicated that the addition of La and Y had a great effect on the refinement of α-Al grains, the modification of eutectic Si phase, and the reduction of ß-Al5FeSi length in Al-Si-Cu alloys. The A380 + 0.6 wt.% La/Y alloy exhibited the best microstructure and mechanical properties. The UTS and EI of the A380 + 0.6 wt.% La/Y alloy were 215.3 MPa and 5.1%, which were 22.9% and 37.8% higher than those of the matrix alloy, respectively. In addition, neither Al11La3 nor Al3Y generated by the addition of La and Y could not serve as the nucleation core of α-Al grains, so the grain refinement of α-Al originated from the growth limitation and constitutional supercooling. Since La and Y promote twinning generation and constitutional supercooling, the eutectic Si phase also changed from stripe-like to short fibrous or even granular and was significantly refined. Furthermore, thermodynamic calculations indicated that the Al11La3 phase was formed first and the Al3Y phase was generated on the Al11La3 phase.

Simulation of infrared spectra of trace impurities in silicon wafers based on the multiple transmission-reflection infrared method.

The content of trace impurities, such as interstitial oxygen and substitutional carbon, in silicon is crucial in determining the mechanical and physical characteristics of silicon wafers. The traditional infrared (IR) method is adopted as a normal means to analyse their concentration at home and abroad, but there are two problems. The first problem is the poor representativeness of a single local sampling point because the impurity distribution in a solid sample is not as uniform as that in a liquid sample. The second problem is that interference fringes appear in the infrared spectra of the sample due to the thin wafer (≤ 300 µm thick). Based on this, controversial issues existed regarding the measured trace impurity concentrations between wafer manufacturers and solar cell assembly businessmen who used silicon sheets made by the former. Therefore, multiple transmission-reflection (MTR) infrared (IR) spectroscopy was proposed to solve the problems mentioned above. In the MTR setup, because light passes through different parts of the silicon chip several times, multiple sampling points make the final result more representative. Moreover, the optical path is lengthened, and the corresponding absorbance is enhanced. In addition to amplification of weak signals, the MTR-IR method can eliminate interference fringes via the integrating sphere effect of its special configuration. The signal-to-noise ratio of the corresponding spectrum is considerably improved due to the aforementioned dual effects. Thus, the accuracy and sensitivity of the detection method for trace impurities in silicon chips are greatly increased. In this study, silicon wafers were placed in the MTR setup, and then, their relative properties at room temperature were investigated. The corresponding theoretical calculation and simulation of infrared spectra of silicon chips were provided. This affords an optional method for the semiconductor material industry to analyse trace impurities in their chips.

Effect of Graphene Oxide Modified with Organic Amine on the Aging Resistance, Rolling Loss and Wet-skid Resistance of Solution Polymerized Styrene-Butadiene Rubber.

Graphene oxide (GO) was modified by p-phenylenediamine (PPD), aiming at improving the wet-skid resistance and reduce the rolling loss of solution polymerized styrene-butadiene rubber (SSBR). PPD with amino groups enabled GO to obtain anti-aging function. The structure of modified GO (PPD-GO) was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and Raman spectroscopy. Mechanical tests showed that the mechanical properties of SSBR before and after aging were improved by adding PPD-GO. The results of thermogravimetric-differential scanning calorimeter synchronization analysis (TGA-DSC) indicated that SSBR/PPD-GO obtained good thermo-oxidative stability. The dynamic mechanical analysis (DMA) of SSBR composites showed that the mechanical loss factor (tanδ) peak moved to high temperature with the content of PPD-GO. The tanδ values of SSBR composites showed that it had a good effect on improving the wet-skid resistance and reducing the rolling loss of SSBR by adjusting the content of PPD-GO. In particular, with the addition of 4 phr GO, SSBR was effectively improved in mechanical properties, aging resistance, wet-skid resistance and low rolling loss.

Adjunctive folate for major mental disorders: A systematic review.

OBJECTIVES: This is a meta-analysis of randomized controlled trials (RCTs) to examine the efficacy and safety of adjunctive folate for three major mental disorders (schizophrenia, bipolar disorder, and major depressive disorder (MDD)). METHODS: Review Manager Program Version 5.3 was used to analyze data. RESULTS: Fourteen studies with 16 RCTs (n = 1,520) on folate for schizophrenia (4 RCTs, n = 210), mood disorders (i.e., unipolar and bipolar depression) (1 RCT, n = 60), bipolar disorder (2 RCTs, n = 189) and MDD (9 RCTs, n = 1,061) were analyzed separately by diagnosis. For schizophrenia, adjunctive folate was not superior to placebo in terms of total psychopathology (standardized mean difference (SMD) = -0.14, 95% confidential interval (CI): -0.67, 0.39; I2 = 30%, P = 0.60), and positive (SMD = 0.09, 95% CI: -0.44, 0.62; I2 = not applicable, P = 0.74), negative (SMD = -0.39, 95% CI:-0.84, 0.05; I2 = 50%, P = 0.08), and general symptom scores (SMD = -0.33, 95%CI:-0.87, 0.20; I2 = not applicable, P = 0.22). For bipolar and unipolar depression, adjunctive folate was significantly superior to placebo in improving depressive symptoms. For bipolar disorder, adjunctive folate was effective in treating the acute phase of mania in bipolar disorder, but not in the acute phase of depression. For MDD, adjunctive folate was significantly superior to placebo in improving depressive symptoms (SMD = -0.38, 95%CI: -0.66, -0.09; I2 = 71%, P = 0.01), which was confirmed in 5 of the 10 subgroups. Discontinuation due to any reason and adverse drug reactions were similar between folate and placebo in each diagnostic category. CONCLUSION: This systematic review found adjunctive folate appeared to be effective and safe for MDD and bipolar manic episode, but it was not effective in treating schizophrenia.

FDA Approval Summary: Tisagenlecleucel for Treatment of Patients with Relapsed or Refractory B-cell Precursor Acute Lymphoblastic Leukemia.

Tisagenlecleucel (Kymriah; Novartis Pharmaceuticals) is a CD19-directed genetically modified autologous T-cell immunotherapy. On August 30, 2017, the FDA approved tisagenlecleucel for treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory in second or later relapse. Approval was based on the complete remission (CR) rate, durability of CR, and minimal residual disease (MRD) <0.01% in a cohort of 63 children and young adults with relapsed or refractory ALL treated on a single-arm trial (CCTL019B2202). Treatment consisted of fludarabine and cyclophosphamide followed 2 to 14 days later by a single dose of tisagenlecleucel. The CR rate was 63% (95% confidence interval, 50%-75%), and all CRs had MRD <0.01%. With a median follow-up of 4.8 months, the median duration of response was not reached. Cytokine release syndrome (79%) and neurologic events (65%) were serious toxicities reported in the trial. With implementation of a Risk Evaluation and Mitigation Strategy, the benefit-risk profile was considered acceptable for this patient population with such resistant ALL. A study of safety with 15 years of follow-up is required as a condition of the approval.See related commentary by Geyer, p. 1133.

Aging-Resistant Functionalized LDH⁻SAS/Nitrile-Butadiene Rubber Composites: Preparation and Study of Aging Kinetics/Anti-Aging Mechanism.

With the aim of improving the anti-aging properties of nitrile-butadiene rubber (NBR), a functional organic filler, namely LDH⁻SAS, prepared by intercalating 4-amino-benzenesulfonic acid monosodium salt (SAS) into layered double hydroxides (LDHs) through anion exchange, was added to nitrile-butadiene rubber (NBR), giving the NBR/LDH⁻SAS composites. Successful preparation of LDH⁻SAS was confirmed by XRD, TGA and FTIR. LDH⁻SAS was well dispersed in the NBR matrix, owing to its strong interaction with the nitrile group of NBR. The obtained NBR/LDH⁻SAS composites exhibited excellent thermo-oxidative aging resistance as shown by TGA-DSC. Further investigation by ATR-FTIR indicated that SAS can capture the radical groups, even during the aging process, which largely accounts for the improved aging resistance.

Growing Embossed Nanostructures of Polymer Brushes on Wet-Etched Silicon Templated via Block Copolymers.

Block copolymer nanolithography has attracted enormous interest in chip technologies, such as integrated silicon chips and biochips, due to its large-scale and mass production of uniform patterns. We further modified this technology to grow embossed nanodots, nanorods, and nanofingerprints of polymer brushes on silicon from their corresponding wet-etched nanostructures covered with pendent SiHx (X = 1-3) species. Atomic force microscopy (AFM) was used to image the topomorphologies, and multiple transmission-reflection infrared spectroscopy (MTR-IR) was used to monitor the surface molecular films in each step for the sequential stepwise reactions. In addition, two layers of polymethacrylic acid (PMAA) brush nanodots were observed, which were attributed to the circumferential convergence growth and the diffusion-limited growth of the polymer brushes. The pH response of PMAA nanodots in the same region was investigated by AFM from pH 3.0 to 9.0.

A model of canine leukocyte telomere dynamics.

Recent studies have found associations of leukocyte telomere length (TL) with diseases of aging and with longevity. However, it is unknown whether birth leukocyte TL or its age-dependent attrition--the two factors that determine leukocyte TL dynamics--explains these associations because acquiring this information entails monitoring individuals over their entire life course. We tested in dogs a model of leukocyte TL dynamics, based on the following premises: (i) TL is synchronized among somatic tissues; (ii) TL in skeletal muscle, which is largely postmitotic, is a measure of TL in early development; and (iii) the difference between TL in leukocytes and muscle (ΔLMTL) is the extent of leukocyte TL shortening since early development. Using this model, we observed in 83 dogs (ages, 4-42 months) no significant change with age in TLs of skeletal muscle and a shorter TL in leukocytes than in skeletal muscle (P<0.0001). Age explained 43% of the variation in ΔLMTL (P<0.00001), but only 6% of the variation in leukocyte TL (P=0.035) among dogs. Accordingly, muscle TL and ΔLMTL provide the two essential factors of leukocyte TL dynamics in the individual dog. When applied to humans, the partition of the contribution of leukocyte TL during early development vs. telomere shortening afterward might provide information about whether the individual's longevity is calibrated to either one or both factors that define leukocyte TL dynamics.

Measurement of telomere length by the Southern blot analysis of terminal restriction fragment lengths.

In this protocol we describe a method to obtain telomere length parameters using Southern blots of terminal restriction fragments (TRFs). We use this approach primarily for epidemiological studies that examine leukocyte telomere length. However, the method can be adapted for telomere length measurements in other cells whose telomere lengths are within its detection boundaries. After extraction, DNA is inspected for integrity, digested, resolved by gel electrophoresis, transferred to a membrane, hybridized with labeled probes and exposed to X-ray film using chemiluminescence. Although precise and highly accurate, the method requires a considerable amount of DNA (3 µg per sample) and it measures both the canonical and noncanonical components of telomeres. The method also provides parameters of telomere length distribution in each DNA sample, which are useful in answering questions beyond those focusing on the mean length of telomeres in a given sample. A skilled technician can measure TRF length in ∼130 samples per week.

Genome-wide association identifies OBFC1 as a locus involved in human leukocyte telomere biology.

Telomeres are engaged in a host of cellular functions, and their length is regulated by multiple genes. Telomere shortening, in the course of somatic cell replication, ultimately leads to replicative senescence. In humans, rare mutations in genes that regulate telomere length have been identified in monogenic diseases such as dyskeratosis congenita and idiopathic pulmonary fibrosis, which are associated with shortened leukocyte telomere length (LTL) and increased risk for aplastic anemia. Shortened LTL is observed in a host of aging-related complex genetic diseases and is associated with diminished survival in the elderly. We report results of a genome-wide association study of LTL in a consortium of four observational studies (n = 3,417 participants with LTL and genome-wide genotyping). SNPs in the regions of the oligonucleotide/oligosaccharide-binding folds containing one gene (OBFC1; rs4387287; P = 3.9 x 10(-9)) and chemokine (C-X-C motif) receptor 4 gene (CXCR4; rs4452212; P = 2.9 x 10(-8)) were associated with LTL at a genome-wide significance level (P < 5 x 10(-8)). We attempted replication of the top SNPs at these loci through de novo genotyping of 1,893 additional individuals and in silico lookup in another observational study (n = 2,876), and we confirmed the association findings for OBFC1 but not CXCR4. In addition, we confirmed the telomerase RNA component (TERC) as a gene associated with LTL (P = 1.1 x 10(-5)). The identification of OBFC1 through genome-wide association as a locus for interindividual variation in LTL in the general population advances the understanding of telomere biology in humans and may provide insights into aging-related disorders linked to altered LTL dynamics.

Preparation of sintered foam materials by alkali-activated coal fly ash.

Coal fly ash from coal fired power stations is a potential raw material for the production of ceramic tiles, bricks and blocks. Previous works have demonstrated that coal fly ash consists mainly of glassy spheres that are relatively resistant to reaction. An objective of this research was to investigate the effect of alkali on the preparation process of the foam material. Moreover, the influence of foam dosage on the water absorption, apparent density and compressive strength was evaluated. The experimental results showed that homogenous microstructures of interconnected pores could be obtained by adding 13 wt.% foaming agent at 1050 degrees C, leading to foams presenting water absorption, apparent density and compressive strength values of about 126.5%, 0.414 g/cm(3), 6.76 MPa, respectively.

An exploratory study of the influence of conversation prosody on emotion and intention identification in schizophrenia.

Emotion perception deficits have been well documented in schizophrenia. However, very little is known about decoding of emotion cues in daily communication in this clinical group. The aim of the current study is to examine whether patients with schizophrenia experience difficulties in decoding other people's emotional cues, such as prosody, in daily conversations. Eighteen patients with schizophrenia and nineteen matched controls were administrated an emotion and intention identification task in a series of conversations with a prosody manipulation and a questionnaire that specifically captured subjective experiences of pleasure. Compared with the healthy controls, the patients with schizophrenia exhibited a chance-level performance in emotion identification in the presence of negative prosody. These findings suggest that patients with schizophrenia have a specific deficit in recognizing negative emotion in conversation.

Emotion categorization perception in schizophrenia in conversations with different social contexts.

OBJECTIVE: The aim of the present study was to investigate whether the boundaries between the happy and angry emotions of schizophrenia would be influenced by social context and the difference in emotion categorization boundaries between schizophrenia patients and healthy controls. METHOD: Eighteen patients with schizophrenia and 16 healthy controls were given a forced-choice emotion identification task in which they were required to listen to a series of conversations with different social contexts. The stimuli were linear morphed facial expressions between 'happy' and 'angry' emotions. For each type of social context, the shift point was used as the parameter to estimate when the subjects began to perceive the morphed facial expression as angry. The response slope was used to estimate how abruptly this change in perception occurred. RESULTS: There was no significant difference in the schizophrenia group in the shift point of emotion categorization perception for four categories of conversations occurring in different social contexts. Compared with the healthy controls, the schizophrenia group demonstrated a steeper response slope at the shift point regardless of the conversation type. CONCLUSION: The patients with schizophrenia were less discriminative in their categorization of emotion perception in conversations with different social contexts. The schizophrenia patients, however, were more alert to angry facial expressions in the process of facial expressions morphing from happy to angry, independent of the social context.

Offspring's leukocyte telomere length, paternal age, and telomere elongation in sperm.

Leukocyte telomere length (LTL) is a complex genetic trait. It shortens with age and is associated with a host of aging-related disorders. Recent studies have observed that offspring of older fathers have longer LTLs. We explored the relation between paternal age and offspring's LTLs in 4 different cohorts. Moreover, we examined the potential cause of the paternal age on offspring's LTL by delineating telomere parameters in sperm donors. We measured LTL by Southern blots in Caucasian men and women (n=3365), aged 18-94 years, from the Offspring of the Framingham Heart Study (Framingham Offspring), the NHLBI Family Heart Study (NHLBI-Heart), the Longitudinal Study of Aging Danish Twins (Danish Twins), and the UK Adult Twin Registry (UK Twins). Using Southern blots, Q-FISH, and flow-FISH, we also measured telomere parameters in sperm from 46 young (<30 years) and older (>50 years) donors. Paternal age had an independent effect, expressed by a longer LTL in males of the Framingham Offspring and Danish Twins, males and females of the NHLBI-Heart, and females of UK Twins. For every additional year of paternal age, LTL in offspring increased at a magnitude ranging from half to more than twice of the annual attrition in LTL with age. Moreover, sperm telomere length analyses were compatible with the emergence in older men of a subset of sperm with elongated telomeres. Paternal age exerts a considerable effect on the offspring's LTL, a phenomenon which might relate to telomere elongation in sperm from older men. The implications of this effect deserve detailed study.

Telomere length and mortality: a study of leukocytes in elderly Danish twins.

Leukocyte telomere length, representing the mean length of all telomeres in leukocytes, is ostensibly a bioindicator of human aging. The authors hypothesized that shorter telomeres might forecast imminent mortality in elderly people better than leukocyte telomere length. They performed mortality analysis in 548 same-sex Danish twins (274 pairs) aged 73-94 years, of whom 204 pairs experienced the death of one or both co-twins during 9-10 years of follow-up (1997-2007). From the terminal restriction fragment length (TRFL) distribution, the authors obtained the mean TRFL (mTRFL) and the mean values of the shorter 50% (mTRFL(50)) and shortest 25% (mTRFL(25)) of TRFLs in the distribution and computed the mode of TRFL (MTRFL). They analyzed the proportions of twin pairs in which the co-twin with the shorter telomeres died first. The proportions derived from the intrapair comparisons indicated that the shorter telomeres predicted the death of the first co-twin better than the mTRFL did (mTRFL: 0.56, 95% confidence interval (CI): 0.49, 0.63; mTRFL(50): 0.59, 95% CI: 0.52, 0.66; mTRFL(25): 0.59, 95% CI: 0.52, 0.66; MTRFL: 0.60, 95% CI: 0.53, 0.67). The telomere-mortality association was stronger in years 3-4 than in the rest of the follow-up period, and it grew stronger with increasing intrapair difference in all telomere parameters. Leukocyte telomere dynamics might help explain the boundaries of the human life span.

The association between physical activity in leisure time and leukocyte telomere length.

BACKGROUND: Physical inactivity is an important risk factor for many aging-related diseases. Leukocyte telomere dynamics (telomere length and age-dependent attrition rate) are ostensibly a biological indicator of human aging. We therefore tested the hypothesis that physical activity level in leisure time (over the past 12 months) is associated with leukocyte telomere length (LTL) in normal healthy volunteers. METHODS: We studied 2401 white twin volunteers, comprising 2152 women and 249 men, with questionnaires on physical activity level, smoking status, and socioeconomic status. Leukocyte telomere length was derived from the mean terminal restriction fragment length and adjusted for age and other potential confounders. RESULTS: Leukocyte telomere length was positively associated with increasing physical activity level in leisure time (P< .001); this association remained significant after adjustment for age, sex, body mass index, smoking, socioeconomic status, and physical activity at work. The LTLs of the most active subjects were 200 nucleotides longer than those of the least active subjects (7.1 and 6.9 kilobases, respectively; P= .006). This finding was confirmed in a small group of twin pairs discordant for physical activity level (on average, the LTL of more active twins was 88 nucleotides longer than that of less active twins; P= .03). CONCLUSIONS: A sedentary lifestyle (in addition to smoking, high body mass index, and low socioeconomic status) has an effect on LTL and may accelerate the aging process. This provides a powerful message that could be used by clinicians to promote the potentially antiaging effect of regular exercise.

Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women.

BACKGROUND: Vitamin D is a potent inhibitor of the proinflammatory response and thereby diminishes turnover of leukocytes. Leukocyte telomere length (LTL) is a predictor of aging-related disease and decreases with each cell cycle and increased inflammation. OBJECTIVE: The objective of the study was to examine whether vitamin D concentrations would attenuate the rate of telomere attrition in leukocytes, such that higher vitamin D concentrations would be associated with longer LTL. DESIGN: Serum vitamin D concentrations were measured in 2160 women aged 18-79 y (mean age: 49.4) from a large population-based cohort of twins. LTL was measured by using the Southern blot method. RESULTS: Age was negatively correlated with LTL (r = -0.40, P < 0.0001). Serum vitamin D concentrations were positively associated with LTL (r = 0.07, P = 0.0010), and this relation persisted after adjustment for age (r = 0.09, P < 0.0001) and other covariates (age, season of vitamin D measurement, menopausal status, use of hormone replacement therapy, and physical activity; P for trend across tertiles = 0.003). The difference in LTL between the highest and lowest tertiles of vitamin D was 107 base pairs (P = 0.0009), which is equivalent to 5.0 y of telomeric aging. This difference was further accentuated by increased concentrations of C-reactive protein, which is a measure of systemic inflammation. CONCLUSION: Our findings suggest that higher vitamin D concentrations, which are easily modifiable through nutritional supplementation, are associated with longer LTL, which underscores the potentially beneficial effects of this hormone on aging and age-related diseases.