Cardioprotection and lifespan extension by the natural polyamine spermidine

Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends the lifespan of mice and exerts cardioprotective effects, reducing cardiac hypertrophy and preserving diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy and mitochondrial respiration, and it also improved the mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin phosphorylation and suppressed subclinical inflammation. Spermidine feeding failed to provide cardioprotection in mice that lack the autophagy-related protein Atg5 in cardiomyocytes. In Dahl salt-sensitive rats that were fed a high-salt diet, a model for hypertension-induced congestive heart failure, spermidine feeding reduced systemic blood pressure, increased titin phosphorylation and prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. In humans, high levels of dietary spermidine, as assessed from food questionnaires, correlated with reduced blood pressure and a lower incidence of cardiovascular disease. Our results suggest a new and feasible strategy for protection against cardiovascular disease

An Untargeted Metabolomics Approach to Characterize Short-Term and Long-Term Metabolic Changes after Bariatric Surgery

<div><p>Bariatric surgery is currently one of the most effective treatments for obesity and leads to significant weight reduction, improved cardiovascular risk factors and overall survival in treated patients. To date, most studies focused on short-term effects of bariatric surgery on the metabolic profile and found high variation in the individual responses to surgery. The aim of this study was to identify relevant metabolic changes not only shortly after bariatric surgery (Roux-en-Y gastric bypass) but also up to one year after the intervention by using untargeted metabolomics. 132 serum samples taken from 44 patients before surgery, after hospital discharge (1–3 weeks after surgery) and at a 1-year follow-up during a prospective study (NCT01271062) performed at two study centers (Austria and Switzerland). The samples included 24 patients with type 2 diabetes at baseline, thereof 9 with diabetes remission after one year. The samples were analyzed by using liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS, HILIC-QExactive). Raw data was processed with XCMS and drift-corrected through quantile regression based on quality controls. 177 relevant metabolic features were selected through Random Forests and univariate testing and 36 metabolites were identified. Identified metabolites included trimethylamine-<i>N</i>-oxide, alanine, phenylalanine and indoxyl-sulfate which are known markers for cardiovascular risk. In addition we found a significant decrease in alanine after one year in the group of patients with diabetes remission relative to non-remission. Our analysis highlights the importance of assessing multiple points in time in subjects undergoing bariatric surgery to enable the identification of biomarkers for treatment response, cardiovascular benefit and diabetes remission. Key-findings include different trend pattern over time for various metabolites and demonstrated that short term changes should not necessarily be used to identify important long term effects of bariatric surgery.</p></div

Multidimensional scaling plots from supervised Random Forests of initial 923 metabolic features show distinct clustering of samples taken before (PRE) and after the surgery for both points in time (POST, FU).

<p>Multidimensional scaling plots from supervised Random Forests of initial 923 metabolic features show distinct clustering of samples taken before (PRE) and after the surgery for both points in time (POST, FU).</p

Metabolites showing a significant decline (FU/PRE) in diabetes remission (R) patients compared to non-remission (N-R).

<p>Above: Metabolite changes over time, below: different metabolite levels for diabetes remission (R), non-remission (N-R) and non-diabetes patients (N-DM)</p

Clinical characteristics of study population, presented in mean (± SD) for each sampling point: PRE (before surgery), POST (1–2 weeks after surgery), FU (one year after surgery) including p-values from paired t-tests.

<p>Clinical characteristics of study population, presented in mean (± SD) for each sampling point: PRE (before surgery), POST (1–2 weeks after surgery), FU (one year after surgery) including p-values from paired t-tests.</p

Boxplots of peak-AUC metabolites related to CVR for three different sampling points.

<p>Boxplots of peak-AUC metabolites related to CVR for three different sampling points.</p

Unidirectional trends of changes in the intensities (peak-AUC) of identified metabolites before and after bariatric surgery, metabolites in bold have previously have been associated with CVR.

<p>Unidirectional trends of changes in the intensities (peak-AUC) of identified metabolites before and after bariatric surgery, metabolites in bold have previously have been associated with CVR.</p

Intermittent Fasting (Alternate Day Fasting) In Healthy, Non-obese Adults: Protocol for a Cohort Trial with an Embedded Randomized Controlled Pilot Trial

<p></p><p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found <a href="https://link.springer.com/article/10.1007/s12325-018-0746-5">here<b>.</b></a> </p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p><br><p></p