Depletion of Rictor, an essential protein component of mTORC2, decreases male lifespan

Rapamycin, an inhibitor of the mechanistic target of rapamycin (mTOR), robustly extends the lifespan of model organisms including mice. We recently found that chronic treatment with rapamycin not only inhibits mTOR complex 1 (mTORC1), the canonical target of rapamycin, but also inhibits mTOR complex 2 (mTORC2) in vivo. While genetic evidence strongly suggests that inhibition of mTORC1 is sufficient to promote longevity, the impact of mTORC2 inhibition on mammalian longevity has not been assessed. RICTOR is a protein component of mTORC2 that is essential for its activity. We examined three different mouse models of Rictor loss: mice heterozygous for Rictor, mice lacking hepatic Rictor, and mice in which Rictor was inducibly deleted throughout the body in adult animals. Surprisingly, we find that depletion of RICTOR significantly decreases male, but not female, lifespan. While the mechanism by which RICTOR loss impairs male survival remains obscure, we find that the effect of RICTOR depletion on lifespan is independent of the role of hepatic mTORC2 in promoting glucose tolerance. Our results suggest that inhibition of mTORC2 signaling is detrimental to males, which may explain in part why interventions that decrease mTOR signaling show greater efficacy in females

A novel rapamycin analog is highly selective for mTORC1 in vivo.

Rapamycin, an inhibitor of mechanistic Target Of Rapamycin Complex 1 (mTORC1), extends lifespan and shows strong potential for the treatment of age-related diseases. However, rapamycin exerts metabolic and immunological side effects mediated by off-target inhibition of a second mTOR-containing complex, mTOR complex 2. Here, we report the identification of DL001, a FKBP12-dependent rapamycin analog 40x more selective for mTORC1 than rapamycin. DL001 inhibits mTORC1 in cell culture lines and in vivo in C57BL/6J mice, in which DL001 inhibits mTORC1 signaling without impairing glucose homeostasis and with substantially reduced or no side effects on lipid metabolism and the immune system. In cells, DL001 efficiently represses elevated mTORC1 activity and restores normal gene expression to cells lacking a functional tuberous sclerosis complex. Our results demonstrate that highly selective pharmacological inhibition of mTORC1 can be achieved in vivo, and that selective inhibition of mTORC1 significantly reduces the side effects associated with conventional rapalogs

Short-term consumption of a plant protein diet does not improve glucose homeostasis of young C57BL/6J mice

Recently, it has become apparent that dietary macronutrient composition has a profound impact on metabolism, health and even lifespan. Work from many laboratories now suggest that dietary protein quality - the precise amino acid composition of the diet, as well as possibly the source of dietary protein - may also be critical in regulating the impact of diet on health. Perhaps in part due to the naturally low methionine content of plants, vegan diets are associated with a decreased risk of diabetes and improved insulin sensitivity, but this association is confounded by the lower overall protein intake of vegans. Here, we test the effect of consuming isocaloric rodent diets with similar amino acid profiles derived from either plant protein or dairy protein. We find that male C57BL/6J mice consuming either diet have similar glycemic control, as assessed by glucose, insulin, and pyruvate tolerance tests, and have similar overall body composition. We conclude that short-term feeding of plant protein has no positive or negative effect on the metabolic health of young male C57BL/6J mice, and suggest that dietary interventions that alter either dietary protein levels or the levels of specific essential amino acids are more likely to improve metabolic health than alterations in dietary protein source

Using experimental manipulation to assess the roles of leaf litter in the functioning of forest ecosystems

The widespread use of forest litter as annual bedding in central Europe for many, centuries gave rise to the first litter manipulation studies, and their results demonstrated that litter and its decomposition are a vital part or ecosystem function. Litter plays two major roles in forest ecosystems: firstly, litterfall is all inherent part of nutrient and carbon cycling, and secondly, litter forms a protective layer oil the soil surface that also regulates microclimatic conditions. By reviewing 152 years of litter manipulation experiments, I show that the effects or manipulating litter stem from changes in one, or both, of these two functions, and interactions between the variables influenced by the accumulation of litter can result in feedback mechanisms that may intensify treatment effects or mask responses, making the interpretation of results difficult. Long-term litter removal increased soil bulk density, overland flow, erosion, and temperature fluctuations and upset the soil water balance, causing lower soil water content during dry periods. Soil pH increased or decreased in response to manipulation treatments depending on forest type and initial soil pH, but unclear why there was no uniform response. Long-term litter harvesting severely depleted the forests of nutrients. Decreases in the concentrations of available P, Ca, Mg, and K in the soil occurred after only three to five years. The decline in soil N occurred over longer periods of time, and the relative loss was greater in soils with high initial nitrogen concentration. Tree growth declined with long-term litter removal, probably due to lower nutrient availability. Litter manipulation also added or removed large amounts of carbon thereby affecting microbial communities and altering soil respiration rates. Litter manipulation experiments have shown that litter cover acts as a physical barrier to the shoot emergence of small-seeded species; further, the microclimate maintained by the litter layer may be Favourable to herbivores and pathogens and is important in determining later seedling survival and performance. Litter manipulation altered the competitive outcomes between tree seedlings and forbs, thereby influencing species composition and diversity; changes in the species composition of understorey vegetation following treatments occurred rapidly. By decreasing substrate availability and altering the microclimate, litter removal changed fungal species composition and diversity and led to a decline in populations of soil fauna. However, litter addition did not provoke an corresponding increase in the abundance or diversity of fungi or soil fauna. Large-scale long-term studies are still needed in order to investigate the interactions between the many variables affected by litter, especially in tropical and boreal forests, which have received little attention. Litter manipulation treatments present an opportunity to assess the effects of increasing primary production in forest ecosystems; specific research aims include assessing the effect of changes in litter inputs on the carbon and nutrient cycles, decomposition processes, and the turnover of organic matter

Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health

Protein-restricted (PR), high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs) is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino acids in the maintenance of metabolic health and suggest that diets specifically reduced in BCAAs, or pharmacological interventions in this pathway, may offer a translatable way to achieve many of the metabolic benefits of a PR diet

The GEOTRACES Intermediate Data Product 2017

Unidad de excelencia María de Maeztu MdM-2015-0552The GEOTRACES Intermediate Data Product 2017 (IDP2017) is the second publicly available data product of the international GEOTRACES programme, and contains data measured and quality controlled before the end of 2016. The IDP2017 includes data from the Atlantic, Pacific, Arctic, Southern and Indian oceans, with about twice the data volume of the previous IDP2014. For the first time, the IDP2017 contains data for a large suite of biogeochemical parameters as well as aerosol and rain data characterising atmospheric trace element and isotope (TEI) sources. The TEI data in the IDP2017 are quality controlled by careful assessment of intercalibration results and multi-laboratory data comparisons at crossover stations. The IDP2017 consists of two parts: (1) a compilation of digital data for more than 450 TEIs as well as standard hydrographic parameters, and (2) the eGEOTRACES Electronic Atlas providing an on-line atlas that includes more than 590 section plots and 130 animated 3D scenes. The digital data are provided in several formats, including ASCII, Excel spreadsheet, netCDF, and Ocean Data View collection. Users can download the full data packages or make their own custom selections with a new on-line data extraction service. In addition to the actual data values, the IDP2017 also contains data quality flags and 1-σ data error values where available. Quality flags and error values are useful for data filtering and for statistical analysis. Metadata about data originators, analytical methods and original publications related to the data are linked in an easily accessible way. The eGEOTRACES Electronic Atlas is the visual representation of the IDP2017 as section plots and rotating 3D scenes. The basin-wide 3D scenes combine data from many cruises and provide quick overviews of large-scale tracer distributions. These 3D scenes provide geographical and bathymetric context that is crucial for the interpretation and assessment of tracer plumes near ocean margins or along ridges. The IDP2017 is the result of a truly international effort involving 326 researchers from 25 countries. This publication provides the critical reference for unpublished data, as well as for studies that make use of a large cross-section of data from the IDP2017. This article is part of a special issue entitled: Conway GEOTRACES - edited by Tim M. Conway, Tristan Horner, Yves Plancherel, and Aridane G. González