Circadian Dysfunction Reduces Lifespan in Drosophila melanogaster

Circadian clocks regulate physiological and behavioral processes in a wide variety of organisms, and any malfunction in these clocks can cause significant health problems. In this paper, we report the results of our study on the physiological consequences of circadian dysfunction (malfunctioning of circadian clocks) in two wild‐type populations of fruit flies (Drosophila melanogaster). We assayed locomotor activity behavior and lifespan among adult flies kept under constant dark (DD) conditions of the laboratory, wherein they were categorized as rhythmic if their activity/rest schedules followed circadian (approximately 24 h) patterns, and as arrhythmic if their activity/rest schedules did not display any pattern. The rhythmic flies from both populations lived significantly longer than the arrhythmic ones. Based on these results, we conclude that circadian dysfunction is deleterious, and proper functioning of circadian clocks is essential for the physiological well being of D. melanogaster.     

Individual- and population-level effects of antibiotics on the rotifers, <Emphasis Type="Italic">Brachionus calyciflorus</Emphasis> and <Emphasis Type="Italic">B. plicatilis</Emphasis>

The toxicity of three common antibiotics (streptomycin sulfate, tetracycline hydrochloride, and tylosin tartrate) to the freshwater rotifer Brachionus calyciflorus and brackish-water rotifer B. plicatilis was investigated using full-lifespan exposure durations. Effects of each antibiotic on lifespan, lifetime reproduction, and Malthusian parameter were assessed at seven nominal concentrations (ranging from 5.6 mg l⁻¹ to 2,000 mg l⁻¹) and a negative control. Lowest Observed Effect Concentrations (LOECs) were determined for reproduction and lifespan, while 1%, 10%, 25%, and 50% Inhibitory Concentrations (IC₁, IC₁₀, IC₂₅, IC₅₀) and 95% confidence intervals were estimated for all three endpoints. LOECs ranged from 5.6 mg l⁻¹ to 90 mg l⁻¹, with all LOECs less than 90 mg l⁻¹ occurring in B. calyciflorus. The lowest IC1 concentrations were 3.91 mg l⁻¹ for the effect of tetracycline on lifetime reproduction in B. calyciflorus and 4.06 mg l⁻¹ for the effect of tylosin on lifetime reproduction in B. plicatilis. Overall, lifetime reproduction was the most sensitive endpoint and the Malthusian parameter was the least sensitive. IC₁ values for lifetime reproduction were roughly one to two orders of magnitude lower than the corresponding IC₅₀ values. Guest editors: S. S. S. Sarma, R. D. Gulati, R. L. Wallace, S. Nandini, H. J. Dumont and R. Rico-Martínez Advances in Rotifer Research     

The genetic basis for mating-induced sex differences in starvation resistance in Drosophila melanogaster

Multiple genetic and environmental factors interact to influence starvation resistance, which is an important determinant of fitness in many organisms, including Drosophila melanogaster. Recent studies have revealed that mating can alter starvation resistance in female D. melanogaster, but little is known about the behavioral and physiological mechanisms underlying such mating-mediated changes in starvation resistance. In the present study, we first investigated whether the effect of mating on starvation resistance is sex-specific in D. melanogaster. As indicated by a significant sex × mating status interaction, mating increased starvation resistance in females but not in males. In female D. melanogaster, post-mating increase in starvation resistance was mainly attributed to increases in food intake and in the level of lipid storage relative to lean body weight. We then performed quantitative genetic analysis to estimate the proportion of the total phenotypic variance attributable to genetic differences (i.e., heritability) for starvation resistance in mated male and female D. melanogaster. The narrow-sense heritability (h²) of starvation resistance was 0.235 and 0.155 for males and females, respectively. Mated females were more resistant to starvation than males in all genotypes, but the degree of such sexual dimorphism varied substantially among genotypes, as indicated by a significant sex × genotype interaction for starvation resistance. Cross-sex genetic correlation was greater than 0 but less than l for starvation resistance, implying that the genetic architecture of this trait was partially shared between the two sexes. For both sexes, starvation resistance was positively correlated with longevity and lipid storage at genetic level. The present study suggests that sex differences in starvation resistance depend on mating status and have a genetic basis in D. melanogaster.     

Mechanisms of amino acid-mediated lifespan extension in Caenorhabditis elegans

Background

Little is known about the role of amino acids in cellular signaling pathways, especially as it pertains to pathways that regulate the rate of aging. However, it has been shown that methionine or tryptophan restriction extends lifespan in higher eukaryotes and increased proline or tryptophan levels increase longevity in C. elegans. In addition, leucine strongly activates the TOR signaling pathway, which when inhibited increases lifespan.

Results

Therefore each of the 20 proteogenic amino acids was individually supplemented to C. elegans and the effects on lifespan were determined. All amino acids except phenylalanine and aspartate extended lifespan at least to a small extent at one or more of the 3 concentrations tested with serine and proline showing the largest effects. 11 of the amino acids were less potent at higher doses, while 5 even decreased lifespan. Serine, proline, or histidine-mediated lifespan extension was greatly inhibited in eat-2 worms, a model of dietary restriction, in daf-16/FOXO, sir-2.1, rsks-1 (ribosomal S6 kinase), gcn-2, and aak-2 (AMPK) longevity pathway mutants, and in bec-1 autophagy-defective knockdown worms. 8 of 10 longevity-promoting amino acids tested activated a SKN-1/Nrf2 reporter strain, while serine and histidine were the only amino acids from those to activate a hypoxia-inducible factor (HIF-1) reporter strain. Thermotolerance was increased by proline or tryptophan supplementation, while tryptophan-mediated lifespan extension was independent of DAF-16/FOXO and SKN-1/Nrf2 signaling, but tryptophan and several related pyridine-containing compounds induced the mitochondrial unfolded protein response and an ER stress response. High glucose levels or mutations affecting electron transport chain (ETC) function inhibited amino acid-mediated lifespan extension suggesting that metabolism plays an important role. Providing many other cellular metabolites to C. elegans also increased longevity suggesting that anaplerosis of tricarboxylic acid (TCA) cycle substrates likely plays a role in lifespan extension.

Conclusions

Supplementation of C. elegans with 18 of the 20 individual amino acids extended lifespan, but lifespan often decreased with increasing concentration suggesting hormesis. Lifespan extension appears to be caused by altered mitochondrial TCA cycle metabolism and respiratory substrate utilization resulting in the activation of the DAF-16/FOXO and SKN-1/Nrf2 stress response pathways.

Electronic supplementary material

The online version of this article (doi:10.1186/s12863-015-0167-2) contains supplementary material, which is available to authorized users.     

Circadian dysfunction reduces lifespan in Drosophila melanogaster

Circadian clocks regulate physiological and behavioral processes in a wide variety of organisms, and any malfunction in these clocks can cause significant health problems. In this paper, we report the results of our study on the physiological consequences of circadian dysfunction (malfunctioning of circadian clocks) in two wild-type populations of fruit flies (Drosophila melanogaster). We assayed locomotor activity behavior and lifespan among adult flies kept under constant dark (DD) conditions of the laboratory, wherein they were categorized as rhythmic if their activity/rest schedules followed circadian (approximately 24 h) patterns, and as arrhythmic if their activity/rest schedules did not display any pattern. The rhythmic flies from both populations lived significantly longer than the arrhythmic ones. Based on these results, we conclude that circadian dysfunction is deleterious, and proper functioning of circadian clocks is essential for the physiological well being of D. melanogaster.     

L-carnosine reduces telomere damage and shortening rate in cultured normal fibroblasts

Telomere is the repetitive DNA sequence at the end of chromosomes, which shortens progressively with cell division and limits the replicative potential of normal human somatic cells. L-carnosine, a naturally occurring dipeptide, has been reported to delay the replicative senescence, and extend the lifespan of cultured human diploid fibroblasts. In this work, we studied the effect of carnosine on the telomeric DNA of cultured human fetal lung fibroblast cells. Cells continuously grown in 20 mM carnosine exhibited a slower telomere shortening rate and extended lifespan in population doublings. When kept in a long-term nonproliferating state, they accumulated much less damages in the telomeric DNA when cultured in the presence of carnosine. We suggest that the reduction in telomere shortening rate and damages in telomeric DNA made an important contribution to the life-extension effect of carnosine.     

The effect of neuronal expression of heat shock proteins 26 and 27 on lifespan, neurodegeneration, and apoptosis in Drosophila

Heat shock proteins (Hsps) are chaperones thought to increase lifespan, enhance stress resistance, and prevent apoptosis and neurodegenerative diseases. Our previous study reported that ubiquitous expression of hsp26 or hsp27 extended Drosophila lifespan. The effect of neuronal expression of hsp26 and hsp27 in Drosophila on the above-mentioned functions has not yet been investigated. Here, we show that neuronal expression of hsp26 or hsp27 improved lifespan and increased resistance to oxidative stress. However, only neuronal expression of hsp27 ameliorated Parkinsonism climbing disorder and attenuated mild polyglutamine-induced toxicity. Additionally, neuronal expression of hsp27 specifically partially rescued hid-induced lethality, but was not able to rescue reaper/grim-induced lethality. However, unlike hsp27, neuronal expression of hsp26 did not rescue hid-induced or reaper/grim-induced lethality. In summary, we demonstrate the functional similarities and differences of neuronal expression of hsp26 and hsp27 in adult Drosophila.     

The mitochondria-targeted antioxidant MitoQ extends lifespan and improves healthspan of a transgenic Caenorhabditis elegans model of Alzheimer disease

β-Amyloid (Aβ)-induced toxicity and oxidative stress have been postulated to play critical roles in the pathogenic mechanism of Alzheimer disease (AD). We investigated the in vivo ability of a mitochondria-targeted antioxidant, MitoQ, to protect against Aβ-induced toxicity and oxidative stress in a Caenorhabditis elegans model overexpressing human Aβ. Impairment of electron transport chain (ETC) enzymatic activity and mitochondrial dysfunction are early features of AD. We show that MitoQ extends lifespan, delays Aβ-induced paralysis, ameliorates depletion of the mitochondrial lipid cardiolipin, and protects complexes IV and I of the ETC. Despite its protective effects on lifespan, healthspan, and ETC function, we find that MitoQ does not reduce DCFDA fluorescence, protein carbonyl levels or modulate steadystate ATP levels or oxygen consumption rate. Moreover, MitoQ does not attenuate mitochondrial DNA (mtDNA) oxidative damage. In agreement with its design, the protective effects of MitoQ appear to be targeted specifically to the mitochondrial membrane and our findings suggest that MitoQ may have therapeutic potential for Aβ- and oxidative stress-associated neurodegenerative disorders, particularly AD.     

A novel arrangement of midgut epithelium and hepatic cells implies a novel regulation of the insulin signaling pathway in long-lived millipedes

Nutrients absorbed by the epithelial cells of the millipede midgut are channeled to a contiguous population of hepatic cells where sugars are stored as glycogen. In insects and other arthropods, however, nutrients absorbed by midgut epithelia are first passed across the epithelial basal surface to the hemolymph before storage in fat body. The inter-digitation of cellular processes at the interface of hepatic and midgut epithelial cells offers a vast surface area for exchange of nutrients. At this interface, numerous small vesicles with the dimensions of exosomes (∼30 nm) may represent the mediators of nutrient exchange. Longevity and the developmental arrest of diapause are associated with reduced insulin signaling. The long lifespans for which millipedes are known may be attributable to a novel pathway with reduced insulin signaling represented by the novel arrangement of hepatic storage cells and midgut epithelial absorbing cells.