67 research outputs found
Diet and Aging
No full textInterventions that extend life span by moderately reduced nutrient intake are often referred to as dietary or calorie restriction. Its efficacy in many species has led to the conclusion that a single, evolutionarily conserved, molecular mechanism operates in all cases to extend life. Here we discuss examples of diet/genotype interactions that show a more complex mechanistic view is required and that mild dietary modifications can dramatically change the interpretation of model organism aging studies
Drosophila as a model for ageing
No full textDrosophila melanogaster has been a key model in developing our current understanding of the molecular mechanisms of ageing. Of particular note is its role in establishing the evolutionary conservation of reduced insulin and IGF-1-like signaling in promoting healthy ageing. Capitalizing on its many advantages for experimentation, more recent work has revealed how precise nutritional and genetic interventions can improve fly lifespan without obvious detrimental side effects. We give a brief summary of these recent findings as well as examples of how they may modify ageing via actions in the gut and muscle. These discoveries highlight how expanding our understanding of metabolic and signaling interconnections will provide even greater insight into how these benefits may be harnessed for anti-ageing interventions
Both overlapping and independent mechanisms determine how diet and insulin-ligand knockouts extend lifespan of Drosophila melanogaster
No full textLifespan in many organisms, including Drosophila melanogaster, can be increased by reduced insulin-IGF-like signaling (IIS) or by changes in diet. Most studies testing whether IIS is involved in diet-mediated lifespan extension employ only a few diets, but recent data shows that a broad range of nutritional environments is required. Here, we present lifespan data of long-lived Drosophila, lacking three of the eight insulin-like peptides [Drosophila insulin-like peptides 2,3,5 (dilp2-3,5)] on nine different diets that surround the optimum for lifespan. Their nutritional content was varied by manipulating sugar and yeast concentrations independently, and thus incorporated changes in both diet restriction and nutrient balance. The mutants were substantially longer-lived than controls on every diet, but the effects on the lifespan response to sugar and yeast differed. Our data illustrates how a greater coverage of diet balance (DB) and restriction can unify differing interpretations of how IIS might be involved in the response of lifespan to diet
Data from: Sex-specific transcriptomic responses to changes in the nutritional environment
No full textMales and females typically pursue divergent reproductive strategies and accordingly require different dietary compositions to maximise their fitness. Here we move from identifying sex-specific optimal diets to understanding the molecular mechanisms that underlie male and female responses to dietary variation in Drosophila melanogaster. We examine male and female gene expression on male-optimal (carbohydrate-rich) and female-optimal (protein-rich) diets. We find that the sexes share a large core of metabolic genes that are concordantly regulated in response to dietary composition. However, we also observe smaller sets of genes with divergent and opposing regulation, most notably in reproductive genes which are over-expressed on each sex's optimal diet. Our results suggest that nutrient sensing output emanating from a shared metabolic machinery are reversed in males and females, leading to opposing diet-dependent regulation of reproduction in males and females. Furt
her analysis and experiments suggest that this reverse regulation occurs via the Tor pathway
Dietary Restriction and Aging: A Unifying Perspective
No full textDietary restriction (DR) and mutations in nutrient signaling pathways can extend healthy life span in diverse organisms. Studying the interaction between these interventions should reveal mechanisms of aging, but has yielded some apparently contradictory results. A multidimensional representation of nutrition, called the geometric framework, can better describe the responses of life span and other traits, including metabolism, and can reconcile these apparent contradictions. We provide examples showing that it is more informative to analyze DR in terms of dietary balance and that dietary optimization for life span is critical for studies examining the biology of aging and other traits
Readers’ attitudes to self-archiving in the UK
No full textThe online self-archiving by authors of their scholarly articles has been proposed as an alternative to author-pays open access publication, but has the potential to undermine journal publisher income if the ready availability of self-archived articles leads to a drop in subscriptions. This study investigated the awareness of self-archiving and use of self-archived articles in a survey of a mainly academic population including both authors and non-authors, and looks at their attitudes to self-archived papers and whether they view them as an authoritative alternative to subscription access. In total, 70% of respondents had heard of self-archiving, though only 15% knew a lot about it, and 71% had used self-archived papers. These proportions are higher than in previous studies, suggesting that awareness has grown. Most self-archived papers used came from websites rather than repositories, particularly among those whose awareness of self-archiving was low. Use of self-archived articles was greater amongst those who had published more papers and also depended strongly on subject field – use and awareness were both particularly low in the field of medicine. People who were more aware of self-archiving were less likely to view the publisher’s official version as the only authoritative version and more likely not to care about the online location of articles. Moreover, authors who had self-archived tended to archive the publisher’s official version regardless of whether they were permitted to. These results suggest that the awareness of self-archiving is currently mostly limited to academic authors and is unlikely to grow beyond this in the short term. However, in the long term, the combination of high rates of self-archiving of the publisher’s official version, coupled with the devaluation of the journal as the authoritative source of material together with increased convenience of access to self-archived material, could result in fewer people accessing articles through subscription-based methods
Models of insulin signalling and longevity
No full textSingle gene mutations that extend lifespan have drastically changed ageing research because they offer potential answers to the questions of why and how we age. Mutations that lower activity of the insulin and insulin-like growth factor signalling (IIS) pathways extend the lifespan of worms, flies and mice. It is possible, therefore, to learn about human ageing from the conserved features of these long-lived models. Here, we summarise the available data in this light
Both overlapping and independent mechanisms determine how diet and insulin-ligand knockouts extend lifespan of Drosophila melanogaster
No full textLifespan in many organisms, including Drosophila melanogaster, can be increased by reduced insulin-IGF-like signaling (IIS) or by changes in diet. Most studies testing whether IIS is involved in diet-mediated lifespan extension employ only a few diets, but recent data shows that a broad range of nutritional environments is required. Here, we present lifespan data of long-lived Drosophila, lacking three of the eight insulin-like peptides [Drosophila insulin-like peptides 2,3,5 (dilp2-3,5)] on nine different diets that surround the optimum for lifespan. Their nutritional content was varied by manipulating sugar and yeast concentrations independently, and thus incorporated changes in both diet restriction and nutrient balance. The mutants were substantially longer-lived than controls on every diet, but the effects on the lifespan response to sugar and yeast differed. Our data illustrates how a greater coverage of diet balance (DB) and restriction can unify differing interpretations of how IIS might be involved in the response of lifespan to diet.</p
Using Doubly-Labeled Water to Measure Energy Expenditure in an Important Small Ectotherm Drosophila melanogaster
No full textEnergy expenditure is a key variable in the study of ageing, and the fruit fly Drosophila melanogaster is a model organism that has been used to make step changes in our understanding of the ageing process. Standard methods for measurement of energy expenditure involve placing individuals in metabolic chambers where their oxygen consumption and CO2 production can be quantified. These measurements require separating individuals from any social context, and may only poorly reflect the environment in which the animals normally live. The doubly-labeled water (DLW) method is an isotope-based technique for measuring energy expenditure which overcomes these problems. However, technical challenges mean that the smallest animals this method has been previously applied to weighed 50-200 mg. We overcame these technical challenges to measure energy demands in Drosophila weighing 0.78 mg. Mass-specific energy expenditure varied between 43 and 65 mW·g(-1). These estimates are considerably higher than estimates using indirect calorimetry of Drosophila in small metabolic chambers (around 18 mW·g(-1)). The methodology we have established extends downwards by three orders of magnitude the size of animals that can be measured using DLW. This approach may be of considerable value in future ageing research attempting to understand the genetic and genomic basis of ageing
A Critical Examination of the Ecclesiology of John Nelson Darby
No full textThis thesis examines the ecclesiology, or doctrine of the church, of John Nelson
Darby (1800-1882), who was one of the leading and most prominent members of the
Plymouth Brethren in the nineteenth century.
The thesis systematically outlines the structure of Darby's thought on the subject of
ecclesiology. It explains how Darby defined the church and understood its nature.
His ecclesiology is shown to be foundational to the system of Dispensationalist
theology in that the church is seen in occupying a period of time unforeseen in
biblical prophecy. Darby's ecclesiology is also shown to be an ecclesiology of crisis
in that he believed that the church had fallen into such a state of ruin that no bodies
existed that could truly be described as churches.
The thesis considers Darby's solution to the ruin or failure of the church found in
'meeting in the name of the Lord.' It examines how Darby's view of how the church
should meet successfully synthesized the conflicting concepts of unity and separation.
It suggests that other writers have not always recognized how Darby distinguished
between separation from individuals and separation from institutions. Nevertheless
while arguing that Darby's ecclesiology achieved a stable synthesis between unity and
separation, it presents a number of practical problems with Darby's ecclesiology.
Attention is given to Darby's teaching on discipline, ministry, church government and
sacraments.
The thesis considers his ecclesiology within a number of contexts. First, its place
within the development of ecclesiology in theological history and in relation
specifically to modem ecclesiologies. Second, in his life and involvement with the
Brethren movement. Third, his role in the development of American fundamentalism,
a major proportion of which has adopted significant aspects of his theology,
particularly Dispensationalism, a form of millennial theology that makes a strong
distinction between the church and the nation of Israel within salvation history. This
thesis argues that while some American fundamentalists adopted Darby's
dispensational views, they found very different practical applications for them in their
ecclesiastical activity. A number of reasons are considered as to why they did not
adopt Darby's ecclesiology in its entirety. Fourthly, the thesis considers the place of
Darby's ecclesiology in relation to other ecclesiastical movements in nineteenth
century Britain. It argues that Darby's ecclesiology shared similar themes to three
ecclesiastical movements
- …
