Moderate exercise improves cardiac hypertrophy in female aged mice

Age-related diastolic dysfunction has a significant impact on the elderly health, in fact the left ventricular filling is impaired, limiting intense exercise tolerance and reducing the quality of life. Pathological hypertrophy is commonly associated with up-regulation of fetal genes, fibrosis, cardiac dysfunction, fat deposits and increased mortality. Regular and moderate physical activity improves cardiac performance in elderly people. Type 5 cyclic nucleotide phosphodiesterase (PDE5) regulates intracellular cGMP levels and its increased expression has an important role in the development of cardiac hypertrophy (1). Our hypothesis is to assess if moderate exercise modulates PDE5 expression and reduces cardiac hypertrophy in old mice. CD1 female mice were grouped in young (2 months) sedentary (YS), young trained (YE), old 20 months sedentary (OS) and old old trained (OE). Exercise was performed at moderate intensity (speed of 13 m/min, for 30 minutes) on tapis roulant for 5 days/week. Morphometric (left ventricular weight/tibial length ratio) and histological (cardiomyocyte size) analyses showed that cardiac hypertrophy is present in OS compared to YS and YE and significantly reduced in OE group compared to OS. Moderate exercise also attenuated cardiac fibrosis in OE group. Molecular analysis revealed that hypertrophic markers such as ANP, BNP, GATA 4 and NKX 2.5 were significantly down-regulated in OE group. SIRT1 and PPARα, two regulators of oxidative stress and fat metabolism, were up-regulated in aged trained mice. PDE5 expression is down-regulated after exercise in OE group. These results suggest that exercise leads to a beneficial effect in old mice. Interestingly PDE5 expression correlates with the anti-hypertrophic effect of training in old mice

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements