16 research outputs found

    Case report: Severe asymptomatic hypertriglyceridemia associated with long-term low-dose rapamycin administration in a healthy middle-aged Labrador retriever

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    Rapamycin is an mTOR inhibitor that has been shown to extend the lifespan of laboratory model organisms. In humans, rapamycin is used at higher doses as an immunosuppressive medication to prevent organ rejection. Numerous adverse effects are seen with rapamycin treatment in humans, with one of the most common being dysregulation of lipid metabolism. In humans, this often manifests as mild to moderate serum lipid elevations, with a small subset developing extreme triglyceride elevations. This case report describes an eight-year-old, castrated male, clinically healthy Labrador retriever who developed severe hypertriglyceridemia associated with low-dose rapamycin administration over a six-month period. During this time, the dog was asymptomatic and displayed no other clinical abnormalities, aside from a progressive lipemia. Within 15 days of discontinuing rapamycin treatment, and with no targeted lipemic intervention, the dog’s lipemia and hypertriglyceridemia completely resolved

    Characterization of plasma thiol redox potential in a common marmoset model of aging☆

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    Due to its short lifespan, ease of use and age-related pathologies that mirror those observed in humans, the common marmoset (Callithrix jacchus) is poised to become a standard nonhuman primate model of aging. Blood and extracellular fluid possess two major thiol-dependent redox nodes involving cysteine (Cys), cystine (CySS), glutathione (GSH) and glutathione disulfide (GSSG). Alteration in these plasma redox nodes significantly affects cellular physiology, and oxidation of the plasma Cys/CySS redox potential (EhCySS) is associated with aging and disease risk in humans. The purpose of this study was to determine age-related changes in plasma redox metabolites and corresponding redox potentials (Eh) to further validate the marmoset as a nonhuman primate model of aging. We measured plasma thiol redox states in marmosets and used existing human data with multivariate adaptive regression splines (MARS) to model the relationships between age and redox metabolites. A classification accuracy of 70.2% and an AUC of 0.703 were achieved using the MARS model built from the marmoset redox data to classify the human samples as young or old. These results show that common marmosets provide a useful model for thiol redox biology of aging

    Invariance and plasticity in the Drosophila melanogaster metabolomic network in response to temperature

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    BACKGROUND: Metabolomic responses to extreme thermal stress have recently been investigated in Drosophila melanogaster. However, a network level understanding of metabolomic responses to longer and less drastic temperature changes, which more closely reflect variation in natural ambient temperatures experienced during development and adulthood, is currently lacking. Here we use high-resolution, non-targeted metabolomics to dissect metabolomic changes in D. melanogaster elicited by moderately cool (18°C) or warm (27°C) developmental and adult temperature exposures. RESULTS: We find that temperature at which larvae are reared has a dramatic effect on metabolomic network structure measured in adults. Using network analysis, we are able to identify modules that are highly differentially expressed in response to changing developmental temperature, as well as modules whose correlation structure is strongly preserved across temperature. CONCLUSIONS: Our results suggest that the effect of temperature on the metabolome provides an easily studied and powerful model for understanding the forces that influence invariance and plasticity in biological networks. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12918-014-0139-6) contains supplementary material, which is available to authorized users

    The effects of graded levels of calorie restriction : III. Impact of short term calorie and protein restriction on mean daily body temperature and torpor use in the C57BL/6 mouse

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    GRANT SUPPORT This work was supported by BBSRC BB009953/1 awarded to JRS and SEM. PK and CD were funded by the Erasmus exchange programme. JRS, SEM, DD, CG, LC, JJDH, YW, DELP, DL and AD are members of the BBSRC China Partnership Award, BB/J020028/1.Peer reviewedPublisher PD

    The effects of graded levels of calorie restriction XV : phase space attractors reveal distinct behavioral phenotypes

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    © The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: [email protected] reviewedPostprin

    Evolution: Aging Up a Tree?

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    SummaryEvolutionary theories of aging predict that species in low-risk habitats will evolve longer lifespans. A new study comparing lifespan in arboreal and terrestrial mammals provides further support for this prediction. But is the prediction valid

    Data from: Past and present resource availability affect mating rate but not choice in Drosophila melanogaster

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    The choices of when, where, and with whom to mate represent some of the most important decisions an individual can make to increase their fitness. Several studies have shown that the resources available to an individual during development can dramatically alter their mating rate later in life, and even the choice of mate. However, an individual’s surroundings and available resources can change rapidly, and it is not clear how quickly the redistribution of resources towards reproduction can change. To address this important question, we measured mating rate and mate choice among Drosophila melanogaster males that were manipulated in terms of both past resources (control vs. starvation) and the resources available during mate choice (food vs. no food). We found that males given access to ample resources prior to mate choice showed higher mating rates than those that were starved, in agreement with previous studies. However, we also found that this effect can be reversed quickly, as starved males given the opportunity to mate in a high-quality environment mated at frequencies equivalent to their fed counterparts. While past and present resources affected mating rate, they did not affect mate choice, as males mated with high quality females at high frequencies regardless of their condition and environment. Our results show that both current condition as well as the promise of future resources can dramatically influence individuals’ investment into reproduction, and that such mating decisions are extremely plastic and reliant on environmental cues
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