Regulation of the one carbon folate cycle as a shared metabolic signature of longevity

The metabolome represents a complex network of biological events that reflects the physiologic state of the organism in health and disease. Additionally, specific metabolites and metabolic signaling pathways have been shown to modulate animal ageing, but whether there are convergent mechanisms uniting these processes remains elusive. Here, we used high resolution mass spectrometry to obtain the metabolomic profiles of canonical longevity pathways in C. elegans to identify metabolites regulating life span. By leveraging the metabolomic profiles across pathways, we found that one carbon metabolism and the folate cycle are pervasively regulated in common. We observed similar changes in long-lived mouse models of reduced insulin/IGF signaling. Genetic manipulation of pathway enzymes and supplementation with one carbon metabolites in C. elegans reveal that regulation of the folate cycle represents a shared causal mechanism of longevity and proteoprotection. Such interventions impact the methionine cycle, and reveal methionine restriction as an underlying mechanism. This comparative approach reveals key metabolic nodes to enhance healthy ageing. Metabolic pathways are closely intertwined with longevity. Here the authors perform metabolomic profiling of canonical longevity pathways and show that folate and methionine cycle intermediates are changed in common, and further, genetic manipulation of pathway enzymes and supplementation with metabolites indicates that they causally regulate longevity

The world karst aquifer mapping project: concept, mapping procedure and map of Europe

Karst aquifers contribute substantially to freshwater supplies in many regions of the world, but are vulnerable to contamination and difficult to manage because of their unique hydrogeological characteristics. Many karst systems are hydraulically connected over wide areas and require transboundary exploration, protection and management. In order to obtain a better global overview of karst aquifers, to create a basis for sustainable international water-resources management, and to increase the awareness in the public and among decision makers, the World Karst Aquifer Mapping (WOKAM) project was established. The goal is to create a world map and database of karst aquifers, as a further development of earlier maps. This paper presents the basic concepts and the detailed mapping procedure, using France as an example to illustrate the step-by-step workflow, which includes generalization, differentiation of continuous and discontinuous carbonate and evaporite rock areas, and the identification of non-exposed karst aquifers. The map also shows selected caves and karst springs, which are collected in an associated global database. The draft karst aquifer map of Europe shows that 21.6% of the European land surface is characterized by the presence of (continuous or discontinuous) carbonate rocks; about 13.8% of the land surface is carbonate rock outcrop

The World Karst Aquifer Mapping project: concept, mapping procedure and map of Europe

Karst aquifers contribute substantially to freshwater supplies in many regions of the world, but are vulnerable to contamination and difficult to manage because of their unique hydrogeological characteristics. Many karst systems are hydraulically connected over wide areas and require transboundary exploration, protection and management. In order to obtain a better global overview of karst aquifers, to create a basis for sustainable international water-resources management, and to increase the awareness in the public and among decision makers, the World Karst Aquifer Mapping (WOKAM) project was established. The goal is to create a world map and database of karst aquifers, as a further development of earlier maps. This paper presents the basic concepts and the detailed mapping procedure, using France as an example to illustrate the step-by-step workflow, which includes generalization, differentiation of continuous and discontinuous carbonate and evaporite rock areas, and the identification of non-exposed karst aquifers. The map also shows selected caves and karst springs, which are collected in an associated global database. The draft karst aquifer map of Europe shows that 21.6% of the European land surface is characterized by the presence of (continuous or discontinuous) carbonate rocks; about 13.8% of the land surface is carbonate rock outcrop

Structural and host rock controls on the distribution, morphology and mineralogy of speleothems in the Castañar Cave (Spain)

The Castañar Cave (central western Spain) formed in mixed carbonate–siliciclastic rocks of Neoproterozoic age. The host rock is finely bedded and shows a complex network of folds and fractures, with a prevalent N150E strike. This structure controlled the development and the maze pattern of the cave, as well as its main water routes. The cave formed more than 350 ka ago as the result of both the dissolution of interbedded carbonates and weathering of siliciclastic beds, which also promoted collapse of the overlying host rock. At present it is a totally vadose hypergenic cave, but its initial development could have been phreatic. The cave's speleothems vary widely in their morphology and mineralogy. In general, massive speleothems (stalactites, stalagmites, flowstones, etc.) are associated with the main fractures of the cave and bedding planes. These discontinuities offer a fairly continuous water supply. Other branching, fibrous, mostly aragonite speleothems, commonly occur in the steeper cave walls and were produced by capillary seepage or drip water. Detailed petrographical and isotope analyses indicate that both aragonite and calcite precipitated as primary minerals in the cave waters. Primary calcite precipitated in waters of low magnesium content, whereas aragonite precipitated from magnesium-rich waters. Differences in isotope values for calcite (−5.2 ‰ for δ18O and −9.6 ‰ for δ13C) and aragonite (δ18O of −4.5 ‰ and δ13C of −3.5 ‰) can be explained by the fact that the more unstable mineral (aragonite) tends to incorporate the heavier C isotope to stabilize its structure or that aragonite precipitates in heavier waters. Changes in the water supply and the chemistry and instability of aragonite caused: (1) inversion of aragonite to calcite, which led to the transformation of aragonite needles into coarse calcite mosaics, (2) micritization, which appears as films or crusts of powdery, opaque calcite, and (3) dissolution. Dolomite, huntite, magnesite and sepiolite were identified within moonmilk deposits and crusts. Moonmilk occurs as a soft, white powder deposit on different types of speleothems, but mostly on aragonite formations. Huntite and magnesite formed as primary minerals, whereas dolomite arose via the replacement of both huntite and aragonite. Owing to its variety of speleothems and location in an area of scarce karstic features, the Castañar Cave was declared a Natural Monument in 1997 and is presently the target of a protection and research programme. Although the main products formed in the cave and their processes are relatively well known, further radiometric data are needed to better constrain the timing of these processes. For example, it is difficult to understand why some aragonite speleothems around 350 ka old have not yet given way to calcite, which indicates that the environmental setting of the cave is still not fully understood.Peer reviewe