Acquired temperature‐sensitive paralysis as a biomarker of declining neuronal function in aging <i>Drosophila</i>

Reenan, Robert A.; Rogina, Blanka

doi:10.1111/j.1474-9726.2008.00368.x

Cited by 15 publications

(24 citation statements)

References 31 publications

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“…Data for ts-paralysis at 25°C were published previously. 10 Whereas mle napts mutants when aged at 25°C only become susceptible to paralysis at 35°C in extreme age, animals reared at a lower temperature show almost complete paralysis at 35°C as early as 10 d in males and 20 d in females ( Fig. 3A and B).…”

Section: Resultsmentioning

confidence: 97%

Effect of sodium channel abundance on Drosophila development, reproductive capacity and aging

Garber

Smith

Reenan

et al. 2012

Fly

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The voltage-gated Na (+) channels (VGSC) are complex membrane proteins responsible for generation and propagation of the electrical signals through the brain, the skeletal muscle and the heart. The levels of sodium channels affect behavior and physical activity. This is illustrated by the maleless mutant allele (mle (napts)) in Drosophila, where the decreased levels of voltage-gated Na(+) channels cause temperature-sensitive paralysis. Here, we report that mle (napts) mutant flies exhibit developmental lethality, decreased fecundity and increased neurodegeneration. The negative effect of decreased levels of Na(+) channels on development and ts-paralysis was more pronounced at 18 and 29°C than at 25°C, suggesting particular sensitivity of the mle (napts) flies to temperatures above and below normal environmental conditions. Similarly, longevity of mle (napts) flies was unexpectedly short at 18 and 29°C compared with flies heterozygous for the mle (napts) mutation. Developmental lethality and neurodegeneration of mle (napts) flies was partially rescued by increasing the dosage of para, confirming a vital role of Na(+) channels in development, longevity and neurodegeneration of flies and their adaptation to temperatures.

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Section: Resultsmentioning

confidence: 97%

Effect of sodium channel abundance on Drosophila development, reproductive capacity and aging

Garber

Smith

Reenan

et al. 2012

Fly

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“…Rather, drd expression appears to be required for the development of one or more adult tissues during metamorphosis, and the improper development of such tissues in drd mutants leads, within 1–2 weeks, to the death of the adult. It has also been reported that appearance of several age-dependent markers or phenotypes is accelerated in drd mutant adults, suggesting that drd mutants age more quickly than wild-type flies (Reenan and Rogina, 2008; Rogina et al, 1997). In light of this finding, our data raise the intriguing possibility that the rate of aging in adults could be controlled to some degree by events that occur during metamorphosis.…”

Section: Discussionmentioning

confidence: 95%

Developmental expression of drop-dead is required for early adult survival and normal body mass in Drosophila melanogaster

Sansone

Blumenthal

2012

Insect Biochemistry and Molecular Biology

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In Drosophila melanogaster, mutations in the gene drop-dead (drd) result in early adult lethality, with flies dying within 2 weeks of eclosion. Additional phenotypes include neurodegeneration, tracheal defects, starvation, reduced body mass, and female sterility. The cause of early lethality and the function of the drd protein remain unknown. In the current study, the temporal profiles of drd expression required for adult survival and body mass regulation were investigated. Knockdown of drd expression by UAS-RNAi transgenes and rescue of drd expression on a drd mutant background by a UAS-drd transgene were controlled with the Heat Shock Protein 70 (Hsp70)-Gal4 driver. Flies were heat-shocked at different stages of their lifecycle, and the survival and body mass of the resulting adult flies were assayed. Surprisingly, the adult lethal phenotype did not depend upon drd expression in the adult. Rather, expression of drd during the second half of metamorphosis was both necessary and sufficient to prevent rapid adult mortality. In contrast, the attainment of normal adult body mass required a different temporal pattern of drd expression. In this case, manipulation of drd expression solely during larval development or metamorphosis had no effect on body mass, while knockdown or rescue of drd expression during all of pre-adult (embryonic, larval, and pupal) development did significantly alter body mass. Together, these results indicate that the adult-lethal gene drd is required only during development. Furthermore, the mutant phenotypes of body mass and lifespan are separable phenotypes arising from an absence of drd expression at different developmental stages.

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“…Drosophila undergo a number of functional declines that correlate with increased age and increased mortality rate, including decreased spontaneous movement, decreased climbing speed, decreased memory, decreased heart function, and decreased reproductive capacity (Grotewiel et al, 2005; Iliadi and Boulianne, 2010; Piazza et al, 2009; Reenan and Rogina, 2008). Correlated molecular changes include decreases in protein turnover system activities (Ubiquitin/proteosome and autophagy/lysosomal), corresponding to the increase in abnormal proteins and the age-related up-regulation of Hsps.…”

Section: Hsps Are Predictive Biomarkers Of Life Spanmentioning

confidence: 99%

Heat shock proteins and Drosophila aging

Tower

2011

Experimental Gerontology

145

109

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Since their discovery in Drosophila, the heat shock proteins (Hsps) have been shown to regulate both stress resistance and life span. Aging is characterized by increased oxidative stress and the accumulation of abnormal (malfolded) proteins, and these stresses induce Hsp gene expression through the transcription factor HSF. In addition, a subset of Hsps is induced by oxidative stress through the JNK signaling pathway and the transcription factor Foxo. The Hsps counteract the toxicity of abnormal proteins by facilitating protein refolding and turnover, and through other mechanisms including inhibition of apoptosis. The Hsps are up-regulated in tissue-specific patterns during aging, and their expression correlates with, and sometimes predicts, life span, making them ideal biomarkers of aging. The tools available for experimentally manipulating gene function and assaying healthspan in Drosophila provides an unparalleled opportunity to further study the role of Hsps in aging.

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Acquired temperature‐sensitive paralysis as a biomarker of declining neuronal function in aging Drosophila

Abstract: SummaryGeneral locomotor activity decreases with normal aging in animals and could be partially explained by decreases in neuronal function.

Cited by 15 publications

References 31 publications

Effect of sodium channel abundance on Drosophila development, reproductive capacity and aging

Effect of sodium channel abundance on Drosophila development, reproductive capacity and aging

Developmental expression of drop-dead is required for early adult survival and normal body mass in Drosophila melanogaster

Heat shock proteins and Drosophila aging

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