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Jacques R Vanfleteren

Publications and source records attributed to Jacques R Vanfleteren.

25 records · Page 2Linked to original sources

No reduction of energy metabolism in Clk mutants.

Mutation in any of the four clock genes (clk-1, clk-2, clk-3, gro-1) causes an average slowing down of many temporal processes, and an increase of mean life span. The latter effect has been linked to the slow phenotype, and it has been reasoned that any reduction of the rate of living would reduce the load of oxidative damage, which is thought to drive the ageing process. To test this model we measured several parameters describing metabolic output in wild type worms and all four Clk mutants. We found no gross changes in metabolic output, as assessed from oxygen consumption and heat production rates, lucigenin-mediated light production capacity, ATP content, and lipofuscin autofluorescence. Catalase and superoxide dismutase (SOD) were variably altered, but not cooperatively, as would be expected to enhance reactive oxygen species (ROS) scavenging activity. Thus we conclude that the prolonged life span of Clk mutants cannot be attributed to reduced metabolic rate or an increased activity of the major antioxidant enzymes catalase and SOD.

Acridines↗

No reduction of metabolic rate in food restricted Caenorhabditis elegans.

Dietary restriction (DR) is the most consistent means of extending life span throughout the animal kingdom. Multiple mechanisms by which DR may act have been proposed but none are clearly predominant. We asked whether metabolic rate and stress resistance is altered in Caenorhabditis elegans in response to DR. DR was imposed in two complementary ways: by growing wild-type worms in liquid medium supplemented with reduced concentrations of bacteria and by using eat-2 mutants, which have a feeding defect. Metabolic rate was not reduced when we fed wild-type worms reduced food and was up-regulated in the eat-2 mutants in liquid culture, as assessed by oxygen consumption rate and heat production. The specific activity levels of the antioxidant enzymes superoxide dismutase (SOD) and catalase showed small increases when we reduced food in wild-type worms, but restricted worms acquired no elevated protection against paraquat and hydrogen peroxide. eat-2 mutants showed elevated specific activities of SOD and catalase relative to wild type in liquid culture. These results indicate that the effects imparted by DR and the eat-2 mutation are not identical, and they contradict, at least in C. elegans, the widespread belief that CR acts by lowering the rate of metabolism.

Aging↗

Axenic growth up-regulates mass-specific metabolic rate, stress resistance, and extends life span in Caenorhabditis elegans.

Culture in axenic medium causes two-fold increases in the length of development and adult life span in Caenorhabditis elegans. We asked whether axenic medium imposes dietary restriction (ADR), and causes changes in metabolic activity and stress resistance. Eat mutants, which have a reduced food intake, were studied in parallel with wild-type worms to assess potential synergistic actions of axenic culture and food restriction. We found that axenic culture enhances metabolic activity as assessed by mass-specific oxygen consumption rate and heat production. Axenic culture also caused higher activities of the antioxidant enzymes superoxide dismutase and catalase, and led to increased resistance to high temperature, which was further exacerbated by mutation in eat-2. These results show that axenic medium up-regulates a variety of somatic maintenance functions including oxidative and thermal stress resistance and that food restriction due to axenic growth and to mutation in eat-2 are very similar but not identical.

Aging↗

Phylogenetic analysis of anostracans (Branchiopoda: Anostraca) inferred from nuclear 18S ribosomal DNA (18S rDNA) sequences.

The nuclear small subunit ribosomal DNA (18S rDNA) of 27 anostracans (Branchiopoda: Anostraca) belonging to 14 genera and eight out of nine traditionally recognized families has been sequenced and used for phylogenetic analysis. The 18S rDNA phylogeny shows that the anostracans are monophyletic. The taxa under examination form two clades of subordinal level and eight clades of family level. Two families the Polyartemiidae and Linderiellidae are suppressed and merged with the Chirocephalidae, of which together they form a subfamily. In contrast, the Parartemiinae are removed from the Branchipodidae, raised to family level (Parartemiidae) and cluster as a sister group to the Artemiidae in a clade defined here as the Artemiina (new suborder). A number of morphological traits support this new suborder. The Branchipodidae are separated into two families, the Branchipodidae and Tanymastigidae (new family). The relationship between Dendrocephalus and Thamnocephalus requires further study and needs the addition of Branchinella sequences to decide whether the Thamnocephalidae are monophyletic. Surprisingly, Polyartemiella hazeni and Polyartemia forcipata ("Family" Polyartemiidae), with 17 and 19 thoracic segments and pairs of trunk limb as opposed to all other anostracans with only 11 pairs, do not cluster but are separated by Linderiella santarosae ("Family" Linderiellidae), which has 11 pairs of trunk limbs. All appear to be part of the Chirocephalidae and share one morphological character: double pre-epipodites on at least part of their legs. That Linderiella is part of the Polyartemiinae suggests that multiplication of the number of limbs occurred once, but was lost again in Linderiella. Within Chirocephalidae, we found two further clades, the Eubranchipus-Pristicephalus clade and the Chirocephalus clade. Pristicephalus is reinstated as a genus.

Animals↗

Assessing metabolic activity in aging Caenorhabditis elegans: concepts and controversies.

It is widely believed that normal by-products of oxidative metabolism and the subsequent molecular damage inflicted by them couple the aging process to metabolic rate. Accordingly, high metabolic rates would be expected to accelerate aging, and life-extending interventions are often assumed to act by attenuating metabolic rate. Notorious examples in Caenorhabditis elegans are food restriction, mutation in the Clock genes and several genes of the insulin-like signalling pathway. Here we discuss how metabolic rate can be accurately measured and normalized, and how to deal with differences in body size. These issues are illustrated using experimental data of the long-lived mutant strains clk-1(e2519) and daf-2(e1370). Appropriate analysis shows that metabolic rates in wildtype and in the clk-1 mutant are very similar. In contrast, the metabolic rate profiles point to a metabolic shift toward enhanced efficiency of oxidative phosphorylation in the daf-2 worms.

Aging↗

Ageing is reversed, and metabolism is reset to young levels in recovering dauer larvae of C. elegans.

The nematode Caenorhabditis elegans responds to unfavourable environmental conditions by arresting development and entering diapause as a dauer larva. Dauers can survive several times the normal life span and the duration of the dauer state has no effect on postdauer life span. This led to the suggestion that dauers are non-ageing, and that dauers eventually perish as the consequence of depletion of stored nutrients. We have investigated physiological changes associated with long-term diapause survival, and found that dauer larvae slowly develop senescence-like symptoms, including decrease of metabolic capacity, aconitase enzyme activity, and ATP stores, and increase of lipofuscin- and oxidised flavin-specific fluorescence. However, these changes are reversed when the dauers recover. Thus senescence can occur before attainment of reproductive maturity, and furthermore, is reversible. Other life processes, including respiration rate and heat output, remain unaltered over four weeks of diapause at 24 degrees C. Possible determinants of the enhanced life maintenance include increased resistance to oxidative stress provided by enhanced superoxide dismutase and catalase activities, and a shift to a highly reducing redox status.

Adenosine Triphosphate↗