Habitual aerobic exercise is associated with enhanced endothelium-dependent dilatation (EDD) in older humans, possibly by increasing nitric oxide bioavailability and reducing oxidative stress. However, the mechanisms involved are incompletely understood. EDD was measured in young (6-8 months) and old (29-32 months) cage control and voluntary wheel running (VR) B6D2F1 mice. Age-related reductions in maximal carotid artery EDD to acetylcholine (74 vs. 96%, P < 0.01) and the nitric oxide (NO) component of EDD (maximum dilatation with ACh and l-NAME minus that with ACh alone was −28% vs. −55%, P < 0.01) were restored in old VR (EDD: 96%, NO: −46%). Nitrotyrosine, a marker of oxidative stress, was increased in aorta with age, but was markedly lower in old VR (P < 0.05). Aortic superoxide dismutase (SOD) activity was greater (P < 0.01), whereas NADPH oxidase protein expression (P < 0.01) and activity (P = 0.05) were lower in old VR vs. old cage control. Increasing SOD (with 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl) and inhibition of NADPH oxidase (with apocynin) improved EDD and its NO component in old cage control, but not old VR mice. VR increased endothelial NO synthase (eNOS) protein expression (P < 0.05) and activation (Ser1177 phosphorylation) (P < 0.05) in old mice. VR did not affect EDD in young mice. Our results show that voluntary aerobic exercise restores the age-associated loss of EDD by suppression of oxidative stress via stimulation of SOD antioxidant activity and inhibition of NADPH oxidase superoxide production. Increased eNOS protein and activation also may contribute to exercise-mediated preservation of NO bioavailability and EDD with ageing.

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Purpose Specimens of a pentastomid, identified as a nymphal Linguatula serrata, have previously been reported from the nasal cavity of the endangered Australian marsupial, the spotted-tail quoll, Dasyurus maculatus. These specimens were made available for morphological and molecular characterisation to confirm their species identity. Methods Specimens were examined by light microscopy. Molecular sequencing attempts were unsuccessful. Results Examination showed that the specimens were adult pentastomes of the genus Linguatula. Morphological differences are reported between these specimens and published measurements of specimens from other hosts collected from the same region. Conclusions This is the first confirmed report of an adult Linguatula pentastome in a native Australian animal. Due to the small number of specimens and the lack of successful molecular characterisation, the pentastomes have been referred to Linguatula sp. until future work can confirm the species identity. The need for combined molecular and morphological analysis of pentastome specimens is reiterated.

Aging may increase vulnerability for developing glucose‐insulin dysfunction with consumption of a high fat or "western" diet (WD). Young (Y, 6‐8 mo, N=4‐8/group) and old (O, 29‐31 mo, N=4‐8/group) B6D2F1 mice were fed normal chow (NC, 14% fat by kcal) or WD (40% fat) for 8 weeks. On NC during glucose tolerance tests the areas under the curves for glucose (AUCg) and insulin (AUCi) were not different (15815±665 vs. 14611±1261 mg/dl*min, Y vs. O, P=0.2) and greater (38.1±4.4 vs. 28.1±1.1 ng/ml*min, P<0.05), respectively, in O mice, but there were no age‐group differences (P=0.49) in glucose infusion rates (GIR) during hyperinsulinemic‐euglycemic clamps (6 mU/kg/min). WD increased AUCg in both Y and O (to 18175±653 and 19947±1889 mg/dl*min, respectively, both P=0.01), but increased the insulin response to a glucose challenge only in O mice (AUCi: 79.1±7.3 ng/ml*min, P<0.01 vs. ONC). Compared with NC, WD markedly reduced GIR in O mice (30±6 vs. 51±5 mg/kg/min, P< 0.05), but only tended to do so in Y mice (37±3 vs. 51±8 mg/kg/min, P< 0.1). The ratio of phosphorylated (ser307) to total insulin receptor substrate‐1, a cellular marker of insulin resistance, was greater after WD vs. NC in adipose tissue of O mice (0.99±0.1 vs. 0.75±0.1, P=0.07), but did not differ with diet in Y (P=0.4). Using two distinct methods for assessing glucose‐insulin function, our results offer strong evidence that aging increases susceptibility to WD‐induced development of insulin resistance. Impaired insulin signaling in adipose tissue may be an important mechanism underlying this effect.NIH AG013038, AG006537, AG015897

Age and high fat, ie. Western, diet (WD) are associated with inflammation and impaired endothelium‐dependent dilation (EDD), whereas aerobic exercise has opposite effects. Activation of the pro‐inflammatory signaling molecule inhibitor of kappa B kinase beta (IKKβ), as modulated by adenosine monophosphate activated protein kinase (AMPK), may contribute to these differential effects. Old (O: 29‐31 mo) B6D2F1 mice fed either normal chow (NC) or WD (40% fat, 8 weeks) either were sedentary (SED) or performed voluntary wheel running (VR). In SED, carotid artery EDD to acetylcholine was reduced after WD (max dilation: 62 ± 8 vs. NC: 76 ± 2%, P < 0.05) and this was associated with increased aortic IKKβ activation (phosphorylated (pSer177/181):total IKKβ: 2.1 ± 0.8 vs. 0.5 ± 0.1 AUs, P = 0.01) and reduced AMPK activation (pThr172:total AMPKα: 0.7 ± 0.1 vs. 1.0 ± 0.1 AUs, P = 0.05). VR improved EDD in both NC (96 ± 2%, P < 0.01) and WD (91 ± 7%, P < 0.05) fed mice, while reducing IKKβ activation by ~60% (P < 0.01 in NC, P = 0.1 in WD) and increasing AMPK activity by 30‐40% (P = 0.1 in NC, P < 0.05 in WD). Here we demonstrate that habitual voluntary aerobic exercise may reverse age‐ and WD‐associated vascular endothelial dysfunction by increasing AMPK activity and inhibiting IKKβ‐linked pro‐inflammatory signaling.NIH AG013038, AG006537, AG015897, AG022241, AG000279