Lifespan extension in Caenorhabditis elegans insulin/IGF-1 signalling mutants is supported by non-vertebrate physiological traits

The insulin/IGF-1 signalling (IIS) pathway connects nutrient levels to metabolism, growth and lifespan in eukaryotes ranging from yeasts to humans, including nematodes such as the genetic model organism Caenorhabditis elegans. The link between ageing and the IIS pathway has been thoroughly studied in C. elegans; upon reduced IIS signalling, a genetic survival program is activated resulting in a drastic lifespan extension. One of the components of this program is the upregulation of antioxidant activity but experiments failed to show a clear causal relation to longevity. However, oxidative damage, such as protein carbonyls, accumulates at a slower pace in long-lived C. elegans mutants with reduced IIS. This is probably not achieved by increased macroautophagy, a process that sequesters cellular components to be eliminated as protein turnover rates are slowed down in IIS mutants. The IIS mutant daf-2, bearing a mutation in the insulin/IGF-1 receptor, recapitulates the dauer survival program, including accumulation of fat and glycogen. Fat can be converted into glucose and glycogen via the glyoxylate shunt, a pathway absent in vertebrates. These carbohydrates can be used as substrates for trehalose synthesis, also absent in mammals. Trehalose, a non-reducing homodimer of glucose, stabilises intracellular components and is responsible for almost half of the lifespan extension in IIS mutants. Hence, the molecular mechanisms by which lifespan is extended under reduced IIS may differ substantially between phyla that have an active glyoxylate cycle and trehalose synthesis, such as ecdysozoans and fungi, and vertebrate species such as mammals

DAF-16/FoxO in Caenorhabditis elegans and its role in metabolic remodeling

DAF-16, the only forkhead box transcription factors class O (FoxO) homolog in Caenorhabditis elegans, integrates signals from upstream pathways to elicit transcriptional changes in many genes involved in aging, development, stress, metabolism, and immunity. The major regulator of DAF-16 activity is the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway, reduction of which leads to lifespan extension in worms, flies, mice, and humans. In C. elegans daf-2 mutants, reduced IIS leads to a heterochronic activation of a dauer survival program during adulthood. This program includes elevated antioxidant defense and a metabolic shift toward accumulation of carbohydrates (i.e., trehalose and glycogen) and triglycerides, and activation of the glyoxylate shunt, which could allow fat-to-carbohydrate conversion. The longevity of daf-2 mutants seems to be partially supported by endogenous trehalose, a nonreducing disaccharide that mammals cannot synthesize, which points toward considerable differences in downstream mechanisms by which IIS regulates aging in distinct groups

Intermediary metabolism

Caenorhabditis elegans has orthologs for most of the key enzymes involved in eukaryotic intermediary metabolism, suggesting that the major metabolic pathways are probably present in this species. We discuss how metabolic patterns and activity change as the worm traverses development and ages, or responds to unfavorable external factors, such as temperature extremes or shortages in food or oxygen. Dauer diapause is marked by an enhanced resistance to oxidative stress and a shift toward microaerobic and anaplerotic metabolic pathways and hypometabolism, as indicated by the increased importance of the malate dismutation and glyoxylate pathways and the repression of citric acid cycle activity. These alterations promote prolonged survival of the dauer larva; some of these changes also accompany the extended lifespan of insulin/IGF-1 and several mitochondrial mutants. We also present a brief overview of the nutritional requirements, energy storage and waste products generated by C. elegans

Routine dipstick urinalysis in daily practice of Belgian occupational physicians

BACKGROUND: Little work has been done to assess the quality of health care and the use of evidence-based methods by occupational physicians in Belgium. Therefore, the main objective is to describe one aspect of occupational health assessments, namely the common use of dipstick urinalysis, and to compare the current practice with international guidelines. METHODS: A self-administered questionnaire was mailed to 211 members of the Scientific Association of Occupational Medicine in the Dutch speaking part of Belgium. RESULTS: A total of 120 occupational physicians responded, giving a response rate of 57%. Dipstick urinalysis was a routine investigation for the vast majority of physicians (69%). All test strips screened for protein and in 90% also for blood. Occupational health services offered clinical tests to satisfy customer wants as international guidelines do not recommend screening for haematuria and proteinuria in asymptomatic adults. A lack of knowledge concerning positive testing and referral criteria was demonstrated in almost half of the study participants. CONCLUSIONS: Belgian occupational physicians still routinely perform dipstick testing although there is no evidence to support this screening in healthy workers. To practice evidence-based medicine, occupational physicians need more instruction and training. Development and implementation of more guidelines is not only of use for the individual practitioner, it may also enhance professionalization and efficiency of occupational health care

Life history trade-offs imposed by dragline use in two money spiders

Trade-offs among life history traits are central to understanding the limits of adaptations to stress. In animals, virtually all decisions taken during life are expected to have downstream consequences. To what degree rare, but energy-demanding, decisions carry over to individual performance is rarely studied in arthropods. We used spiders as a model system to test how single investments in silk use - for dispersal or predator escape - affect individual performance. Silk produced for safe lines and as threads for ballooning is of the strongest kind and is energetically costly, especially when resources are limited. We induced dragline spinning in two species of money spider at similar quantities to that under natural conditions and tested trade-offs with lifespan and egg sac production under unlimited prey availability and a dietary restriction treatment. We demonstrate strong trade-offs between dragline spinning and survival and fecundity. Survival trade-offs were additive to those imposed by the dietary treatment, but a reduction in eggs produced after silk use was only prevalent under conditions where food was restricted during the spider's life. Because draglines are not recycled after their use for dispersal or predator escape, their spinning incurs substantial fitness costs in dispersal, especially in environments with prey limitation. Rare but energetically costly decisions related to dispersal or predator escape may thus carry over to adult performance and explain phenotypic heterogeneity in natural populations

Irreducible incoherence and intelligent design : a look into the conceptual toolbox of a pseudoscience

The concept of Irreducible Complexity (IC) has played a pivotal role in the resurgence of the creationist movement over the past two decades. Evolutionary biologists and philosophers have unambiguously rejected the purported demonstration of “intelligent design” in nature, but there have been several, apparently contradictory, lines of criticism. We argue that this is in fact due to Michael Behe's own incoherent definition and use of IC. This paper offers an analysis of several equivocations inherent in the concept of Irreducible Complexity and discusses the way in which advocates of the Intelligent Design Creationism (IDC) have conveniently turned IC into a moving target. An analysis of these rhetorical strategies helps us to understand why IC has gained such prominence in the IDC movement, and why, despite its complete lack of scientific merits, it has even convinced some knowledgeable persons of the impending demise of evolutionary theory

Grist to the mill of anti-evolutionism: the failed strategy of ruling the supernatural out of science by philosophical fiat

According to a widespread philosophical opinion, science is strictly limited to investigating natural causes and putting forth natural explanations. Lacking the tools to evaluate supernatural claims, science must remain studiously neutral on questions of metaphysics. This (self-imposed) stricture, which goes under the name of ‘methodological naturalism’, allows science to be divorced from metaphysical naturalism or atheism, which many people tend to associate with it. However, ruling the supernatural out of science by fiat is not only philosophically untenable, it actually provides grist to the mill of anti-evolutionism. The philosophical flaws in this conception of methodological naturalism have been gratefully exploited by advocates of Intelligent Design Creationism to bolster their false accusations of naturalistic bias and dogmatism on the part of modern science. We argue that it promotes a misleading view of the scientific endeavor and is at odds with the foremost arguments for evolution by natural selection. Reconciling science and religion on the basis of such methodological strictures is therefore misguided

The modern versus extended evolutionary synthesis : sketch of an intra-genomic gene's eye view for the evolutionary-genetic underpinning of epigenetic and developmental evolution

Studying the phenotypic evolution of organisms in terms of populations of genes and genotypes, the Modern Synthesis (MS) conceptualizes biological evolution in terms of 'inter-organismal' interactions among genes sitting in the different individual organisms that constitute a population. It 'black-boxes' the complex 'intra-organismic' molecular and developmental epigenetics mediating between genotypes and phenotypes. To conceptually integrate epigenetics and evo-devo into evolutionary theory, advocates of an Extended Evolutionary Synthesis (EES) argue that the MS's reductive gene-centrism should be abandoned in favor of a more inclusive organism-centered approach. To push the debate to a new level of understanding, we introduce the evolutionary biology of 'intra-genomic conflict' (IGC) to the controversy. This strategy is based on a twofold rationale. First, the field of IGC is both ‘gene-centered’ and 'intra-organismic' and, as such, could build a bridge between the gene-centered MS and the intra-organismic fields of epigenetics and evo-devo. And second, it is increasingly revealed that IGC plays a significant causal role in epigenetic and developmental evolution and even in speciation. Hence, to deal with the ‘discrepancy’ between the ‘gene-centered’ MS and the ‘intra-organismic’ fields of epigenetics and evo-devo, we sketch a conceptual solution in terms of ‘intra-genomic conflict and compromise’ – an ‘intra-genomic gene’s eye view’ that thinks in terms of intra-genomic ‘evolutionarily stable strategies’ (ESSs) among numerous and various DNA regions and elements – to evolutionary-genetically underwrite both epigenetic and developmental evolution, as such questioning the ‘gene-de-centered’ stance put forward by EES-advocates