Still Pondering an Age-Old Question

A theory of trade-offs to explain why we age has spurred 50 years of interdisciplinary research in evolution and molecular genetics

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

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

The effects of graded levels of calorie restriction : IV. Non-linear change in behavioural phenotype of mice in response to short-term calorie restriction

We would like to acknowledge the BSU staff for their invaluable help with caring for the animals. The work was supported by the UK Biotechnology and Biological Sciences Research Council BBSRC (BB/G009953/1 and BB/J020028/1).Peer reviewedPublisher PD

The effects of graded levels of calorie restriction : XI. Evaluation of the main hypotheses underpinning the life extension effects of CR using the hepatic transcriptome

We would like to acknowledge the BSU staff for their invaluable help with caring for the animals.Peer reviewedPublisher PD

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

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

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

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

The effects of graded levels of calorie restriction : V. Impact of short term calorie and protein restriction on physical activity in the C57BL/6 mouse

Peer reviewedPublisher PD

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

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 : II. Impact of short term calorie and protein restriction on circulating hormone levels, glucose homeostasis and oxidative stress in male C57BL/6 mice

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