The flavonoid 4,4′-dimethoxychalcone promotes autophagy-dependent longevity across species

Ageing constitutes the most important risk factor for all major chronic ailments, including malignant, cardiovascular and neurodegenerative diseases. However, behavioural and pharmacological interventions with feasible potential to promote health upon ageing remain rare. Here we report the identification of the flavonoid 4,4′- dimethoxychalcone (DMC) as a natural compound with anti-ageing properties. External DMC administration extends the lifespan of yeast, worms and flies, decelerates senescence of human cell cultures, and protects mice from prolonged myocardial ischaemia. Concomitantly, DMC induces autophagy, which is essential for its cytoprotective effects from yeast to mice. This pro-autophagic response induces a conserved systemic change in metabolism, operates independently of TORC1 signalling and depends on specific GATA transcription factors. Notably, we identify DMC in the plant Angelica keiskei koidzumi, to which longevity- and health-promoting effects are ascribed in Asian traditional medicine. In summary, we have identified and mechanistically characterised the conserved longevity-promoting effects of a natural anti-ageing drug

Assessment of Two Different Glucagon Assays in Healthy Individuals and Type 1 and Type 2 Diabetes Patients

Methods for glucagon analysis suffered in the past from lack of specificity and a narrow sensitivity range, which has led to inaccurate results and to the suggestion that type 1 diabetes (T1D) and type 2 diabetes (T2D) patients have elevated fasting glucagon levels. However, the availability of more specific and more sensitive methods to detect intact glucagon has shown that actual glucagon levels are lower than previously assumed. This study aimed to characterize fasting plasma glucagon levels in healthy individuals and T1D and T2D patients with two different glucagon assays. The study included 20 healthy individuals, 20 T1D and 20 T2D patients. Blood was collected under fasting conditions. A double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) and a conventional radioimmunoassay (RIA) were used. A significant difference in fasting glucagon levels between healthy individuals and T2D was observed by ELISA, but not by RIA. ELISA also yielded lower glucagon levels in healthy individuals than in T1D and T2D patients which RIA did not. RIA produced significantly (p = 0.0001) higher overall median glucagon values than ELISA in a pooled analysis. These results underline the notion that the choice of selective laboratory methods is highly relevant for mechanistic endocrine research

European Journal of Neurology / Healthier rhythm, healthier brain? : Integrity of circadian melatonin and temperature rhythms relates to the clinical state of braininjured patients

Background Healthy circadian rhythmicity has been suggested to relate to a better state of braininjured patients and to support the emergence of consciousness in patient groups characterized by a relative instability thereof such as patients with disorders of consciousness (DOC). Methods Going beyond earlier studies, a systemslevel perspective was adopted and, using multilevel modelling, the joint predictive value of three indices of circadian rhythm integrity derived from skin temperature variations, melatoninsulfate secretion, and physical activity (wrist actigraphy) patterns was evaluated for the behaviourally assessed state [Coma Recovery Scale Revised (CRSR) score] of DOC patients [13 unresponsive wakefulness syndrome; seven minimally conscious (exit) state]. Additionally, it was assessed in a subset of 16 patients whether patients behavioural repertoire (CRSR score) varied (i) with time of day or (ii) offset from the body temperature maximum (BTmax), i.e. when cognitive performance is expected to peak. Results The results reveal that better integrity of circadian melatoninsulfate and temperature rhythms relate to a richer behavioural repertoire. Moreover, higher CRSR scores are, by trend, related to assessments taking place at a later daytime or deviating less from the prespecified time of occurrence of BTmax. Conclusions In conclusion, the results suggest that therapeutic approaches aimed at improving circadian rhythms in braininjured patients are promising and should be implemented in hospitals or nursing homes. Beyond this, it might be helpful to schedule diagnostic procedures and therapies around the (preassessed) BTmax (4 pm in healthy individuals) as this is when patients should be most responsive.W 1223G16Y00777(VLID)354656