Epigenetic age acceleration and metabolic syndrome in the coronary artery risk development in young adults study.

BACKGROUND: The metabolic syndrome (MetS) is a collection of metabolic disturbances that can lead to various cardiovascular diseases. Previous studies have shown a more adverse metabolic risk profile is associated with more advanced biological aging. The associations between epigenetic biomarkers of age with MetS, however, are not well understood. We therefore investigated the associations between epigenetic age acceleration and MetS severity score and incident MetS. RESULTS: A subset of study participants with available whole blood at examination years 15 and 20 from the Coronary Artery Risk Development in Young Adults Study underwent epigenomic profiling using the Illumina MethylationEPIC Beadchip (~ 850,000 sites). Intrinsic and extrinsic epigenetic age acceleration (IEAA and EEAA) were calculated from DNA methylation levels. The MetS severity score was positively associated with IEAA at years 15 (P = 0.016) and 20 (P = 0.016) and EEAA at year 20 (P = 0.040) in cross-sectional analysis. IEAA at year 20 was significantly associated with incident MetS at year 30 (OR = 1.05 [95% CI 1.01, 1.10], P = 0.028). CONCLUSIONS: To our knowledge, this is the first report of the longitudinal association between epigenetic age acceleration and MetS. These findings suggest that a higher MetS severity score is associated with accelerated epigenetic aging and such aging may play a role in the development of metabolic disorders, potentially serving as a useful biomarker of and early detection tool for future MetS.

Spatial distribution of DDT in sediments from estuarine rivers of central Florida.

Sediments may act as both a carrier for and a potential source of contaminants such as toxic organics in aquatic environments. This study investigated the spatial distribution of the pesticide DDT [1,1, 1-trichloro-2,2-bis(p-chlorophenyl)ethane] in sediments from the Cedar and Ortega Rivers located in the lower St. Johns River basin, Florida, USA, using field measurements and three-dimensional kriging analysis. High DDT concentrations were found near the junction of the Cedar and Ortega Rivers and at the north end of the Ortega River in the upper 0.5 m of the sediments, indicating that the sediment was enriched with DDT in the top layer although use of this chlorinated compound was banned in 1972. Further study revealed that the influence of sediment grain size or texture on DDT contamination was negligible in this river system and no linear correlations existed among DDT and its metabolites such as DDD [1,1-dichloro-2,2-bis(p-chlorophenyl)ethane] and DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene]. Comparison of three-dimensional distribution of DDT content to the Florida sediment quality assessment guideline or probable effect level (PEL) showed several "hot spots" in the Ortega River sediments, where DDT contents exceeded the PEL value of 4.78 microg kg(-1). Such contamination may pose a significant hazard to aquatic life.

An enteric occult reflex underlies accommodation and slow transit in the distal large bowel.

BACKGROUND & AIMS: Transit of fecal material through the human colon takes > or =30 hours, whereas transit through the small intestine takes 24 hours. The mechanisms underlying colonic storage and slow transit have yet to be elucidated. Our aim was to determine whether an intrinsic neural mechanism underlies these phenomena. METHODS: Recordings were made from circular muscle (CM) cells and myenteric neurons in the isolated guinea pig distal colon using intracellular recordings and Ca(2+) imaging techniques. Video imaging was used to determine the effects of colonic filling and pellet transit. RESULTS: Circumferential stretch generated ongoing oral excitatory and anal inhibitory junction potentials in the CM. The application of longitudinal stretch inhibited all junction potentials. N-omega-nitro-L-arginine (100 micromol/L) completely reversed the inhibitory effects of longitudinal stretch suggesting that nitric oxide (NO) inhibited interneurons controlling peristaltic circuits. Ca(2+) imaging in preparations that were stretched in both axes revealed ongoing firing in nNOS +ve descending neurons, even when synaptic transmission was blocked. Inhibitory postsynaptic potentials were evoked in mechanosensitive interneurons that were blocked by N-omega-nitro-L-arginine (100 micromol/L). Pellet transit was inhibited by longitudinal stretch. Filling the colon with fluid led to colonic elongation and an inhibition of motility. CONCLUSIONS: Our data support the novel hypothesis that slow transit and accommodation are generated by release of NO from descending (nNOS +ve) interneurons triggered by colonic elongation. We refer to this powerful inhibitory reflex as the intrinsic occult reflex (hidden from observation) because it withdraws motor activity from the muscle.

Pharmacological properties of nicotinic acetylcholine receptors expressed by guinea pig small intestinal myenteric neurons.

The electrophysiological and pharmacological properties of nicotinic acetylcholine receptors (nAChRs) were studied in guinea pig small intestinal myenteric neurons maintained in culture or in acutely isolated preparations. Acetylcholine and nicotine caused inward currents that desensitized in approximately 4 s. The current-voltage (I-V) relationship rectified inwardly with a reversal potential near 0 mV. The agonist rank order potency was 1,1-dimethyl-4-phenyl-piperazinium > acetylcholine = nicotine >> cytisine. Agonist-induced currents were blocked by nAChR antagonists with a rank order potency of mecamylamine > hexamethonium > dihydro-beta-erythroidine (DHbetaE); mecamylamine and DHbetaE exhibit high potency at beta4 and beta2 subunit-containing nAChRs, respectively. alpha-Bungarotoxin (0.1 microM) or alpha-methyllycaconitine (0.1 microM), antagonists that block nAChRs containing alpha7 subunits, did not affect acetylcholine-induced responses. Immunohistochemical studies revealed that nearly every neuron in culture was labeled by an antibody (mAb35) that recognizes nAChR alpha3 and alpha5 subunits. Antibodies selective for alpha3, alpha5, or beta2 subunits also stained most neurons, whereas an alpha7 subunit antibody revealed very few neurons. In neurons in the intact myenteric plexus from newborn and adult guinea pigs, local application of acetylcholine (1 mM) and cytisine (1 mM) caused similar amplitude depolarizations, and these responses were blocked by nAChR antagonists with a rank order potency of mecamylamine > hexamethonium > DHbetaE. These data indicate that myenteric neurons maintained in culture predominantly express nAChRs composed of alpha3, alpha5, beta2, and beta4 subunits. These subunits may be in a homogeneous population of receptors with unique pharmacological properties, or multiple receptors of different subunit composition may be expressed by individual neurons.