87 research outputs found
Grainyhead 1 acts as a drug-inducible conserved transcriptional regulator linked to insulin signaling and lifespan
No full textAging is impacted by interventions across species, often converging on metabolic pathways. Transcription factors regulate longevity yet approaches for their pharmacological modulation to exert geroprotection remain sparse. We show that increased expression of the transcription factor Grainyhead 1 (GRH-1) promotes lifespan and pathogen resistance in Caenorhabditis elegans. A compound screen identifies FDA-approved drugs able to activate human GRHL1 and promote nematodal GRH-1-dependent longevity. GRHL1 activity is regulated by post-translational lysine methylation and the phosphoinositide (PI) 3-kinase C2A. Consistently, nematodal longevity following impairment of the PI 3-kinase or insulin/IGF-1 receptor requires grh-1. In BXD mice, Grhl1 expression is positively correlated with lifespan and insulin sensitivity. In humans, GRHL1 expression positively correlates with insulin receptor signaling and also with lifespan. Fasting blood glucose levels, including in individuals with type 2 diabetes, are negatively correlated with GRHL1 expression. Thereby, GRH-1/GRHL1 is identified as a pharmacologically malleable transcription factor impacting insulin signaling and lifespan
Antidepressants of the serotonin-antagonist type increase body fat and decrease lifespan of adult Caenorhabditis elegans.
No full textIt was recently suggested that specific antidepressants of the serotonin-antagonist type, namely mianserin and methiothepin, may exert anti-aging properties and specifically extend lifespan of the nematode C.elegans by causing a state of perceived calorie restriction (Petrascheck M, Ye X, Buck LB: An antidepressant that extends lifespan in adult Caenorhabditis elegans; Nature, Nov 22, 2007;450(7169):553-6, PMID 18033297). Using the same model organism, we instead observe a reduction of life expectancy when employing the commonly used, standardized agar-based solid-phase assay while applying the same or lower concentrations of the same antidepressants. Consistent with a well-known side-effect of these compounds in humans, antidepressants not only reduced lifespan but also increased body fat accumulation in C. elegans reflecting the mammalian phenotype. Taken together and in conflict with previously published findings, we find that antidepressants of the serotonin-antagonist type not only promote obesity, but also decrease nematode lifespan
New insights into the evaluation of broad QRS complexes:relevance for arrhythmia management
No full textPreserved parasympathetic cardiac innervation after atrioventricular node modification : evidence from circle maps of respiratory sinus arrhythmia
No full textIntroduction: Respiratory sinus arrhythmia (RSA) and heart rate variability (HRV) are parameters of autonomic cardiac innervation. They decrease with age and after atrioventricular nodal modification (AVNM) suggesting vagal denervation in both situations. We hypothesized, however, that AVNM causes only a transient, functional decline in vagal activity, whereas aging causes permanent vagal denervation. A new method of analyzing RSA phase dynamics based on circle maps (CM) can potentially differentiate between both forms of reduced vagal activity.Methods: In 18 younger and 14 older healthy control subjects 24-hour Holter ECGs were recorded for HRV analysis. Repeated measurements of RSA were acquired during paced breathing (PB). In 16 consecutive patients undergoing AVNM the same measurements were applied before, 1 day and 3 months after the procedure. CM were calculated from consecutive RR intervals and the similarity between different CM quantified by the Kullback information gain (KIG).Results: HRV analysis revealed lower HF bands, LF bands and RSA amplitudes in older vs. younger control subjects. KIG revealed less similarity between younger and older control subjects than within the respective age groups. After AVNM a decrease in HF bands was noted in HRV analysis. Three months after AVNM, HF bands returned to pre-ablation values. CM obtained before and 1 day after AVNM displayed comparable similarity to CM acquired 1 day before and 3 months after ablation.Conclusions: In contrast to conventional HRV parameters, CM of RSA are not altered by ablation in the posteroseptal space but by aging. Thus, this new method appears to differentiate between transient autonomic modification and chronic denervation
Lonidamine Extends Lifespan of Adult Caenorhabditis elegans by Increasing the Formation of Mitochondrial Reactive Oxygen Species
No full textObservación de la autofocalización en azul de metileno utilizando "Z SCAN"
No full textDentro de la enseñanza de la física es común modelar los fenómenos considerando tan solo su ca-rácter lineal, debido a que los efectos de orden superior, generalmente pasan desapercibidos. Exis-ten sin embargo otros fenómenos que son de carácter evidentemente no lineal y que pueden utili-zarse para ilustrar este comportamiento de la naturaleza. En este trabajo se presentan los resultados obtenidos al implementar la técnica denominada "z scan" para observar el efecto de autofocaliza-ción que presentan soluciones de azul de metileno en diferentes concentraciones. Como fuente de iluminación se utilizó un láser de He-Ne de 5 mW y la detección de la intensidad se realizó por medio de un fotodiodo pin. Los resultados obtenidos permiten observar la presencia de este fenó-meno no lineal de una forma sencilla y utilizando equipos de bajo costo que usualmente se encuen-tran en laboratorios de enseñanz
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