Targeted neuronal gene expression and longevity in Drosophila

Phillips, J. P.; Parkes, Tony L.; Hilliker, Arthur J.

doi:10.1016/s0531-5565(00)00117-0

Cited by 65 publications

(41 citation statements)

References 23 publications

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“…Here we demonstrated for the first time that the expression and the activity of MnSOD were up-regulated by the mutation introduced into the kinase domain of the IR gene in mice. Transgenic flies, which overexpressed Cu/ZnSOD in motor neurons, survived 40% longer than control fruit flies, whereas transgenic flies that overexpressed MnSOD in motor neurons survived 30% longer than control flies (22,23). The up-regulation of MnSOD may confer an extension of lifespan in Drosophila.…”

Section: Resultsmentioning

confidence: 99%

Estrogen, Insulin, and Dietary Signals Cooperatively Regulate Longevity Signals to Enhance Resistance to Oxidative Stress in Mice

Baba

Shimizu

Suzuki

et al. 2005

Journal of Biological Chemistry

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To investigate the biological significance of a longevity mutation found in daf-2 of Caenorhabditis elegans, we generated a homologous murine model by replacing Pro-1195 of insulin receptors with Leu using a targeted knock-in strategy. Homozygous mice died in the neonatal stage from diabetic ketoacidosis, whereas heterozygous mice showed the suppressed kinase activity of the insulin receptor but grew normally without spontaneously developing diabetes during adulthood. We examined heterozygous insulin receptor mutant mice for longevity phenotypes. Under 80% oxygen, mutant female mice survived 33.3% longer than wild-type female mice, whereas mutant male mice survived 18.2% longer than wild-type male mice. These results suggested that mutant mice acquired more resistance to oxidative stress, but the benefit of the longevity mutation was more pronounced in females than males. Manganese superoxide dismutase activity in mutant mice was significantly upregulated, suggesting that the suppressed insulin signaling leads to an enhanced antioxidant defense. To analyze the molecular basis of the gender difference, we administered estrogen to mutant mice. It was found that the survival of mice under 80% oxygen was extended when they were administered estradiol. In contrast, mutant and wild-type female mice showed shortened survivals when their ovaries were removed. The influence of estrogen is remarkable in mutant mice compared with wild-type mice, suggesting that estrogen modulates insulin signaling in mutant mice. Furthermore, we showed additional extension of survival under oxidative conditions when their diet was restricted. Collectively, we show that three distinct signals; insulin, estrogen, and dietary signals work in independent and cooperative ways to enhance the resistance to oxidative stress in mice.

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Section: Resultsmentioning

confidence: 99%

Estrogen, Insulin, and Dietary Signals Cooperatively Regulate Longevity Signals to Enhance Resistance to Oxidative Stress in Mice

Baba

Shimizu

Suzuki

et al. 2005

Journal of Biological Chemistry

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“…This suggests that the gene is essential for survival but its full expression exceeds optimum levels. It is unclear why antioxidant intervention by mth mutation leads to improved sensorimotor performance during early stages of life when These results are also informative when compared to patterns of functional decline observed for another lifeextended Drosophila line that carries the human gene superoxide dismutase (SOD1), an enzyme whose function is to remove oxidants from the system (Mccord and Fridovic 1969;Parkes et al 1998;Phillips et al 2000). While broad expression of the human SOD1 gene has no effect on Drosophila longevity (Kirby et al 2008) selective expression of this gene in motorneurons extends lifespan by 40 % (Parkes et al 1998).…”

Section: Discussionmentioning

confidence: 99%

“…The wild-type Drosophila has a maximum lifespan of approximately 1.5 to 2 months, aauditory, and memory), and a high homology of genes to other species including mammals (Rose et al 1992;Curtsinger et al 1995;Osiewacz 1997;Parkes et al 1998;Butler 1999;Phillips et al 2000). Fortini et al (2000), for example, have reported that approximately 65 % of human disease genes are conserved in Drosophila (187 of 287 examined).…”

Section: Introductionmentioning

confidence: 99%

“…These studies have identified genes that extend lifespan between 35 % to 60 % by a variety of mechanisms including antioxidant intervention in aerobic cells, e.g., motorneurons (superoxide dismutase gene; Parkes et al 1998;Phillips et al 2000), modulating metabolic state (Rogina et al 2002; the INDY gene: I'm not dead yet), and controlling synaptic efficacy (Song et al 2002; methuselah) among others (Clancy et al 2001;Kapahi et al 2004;Wang et al 2003;Giannakou et al 2004). While a large number of studies have investigated the genetic, biochemical, and neural mechanisms of life-extending genes, much less is known about their influence on sensory and behavioral abilities of Drosophila throughout its lifespan.…”

Section: Introductionmentioning

confidence: 99%

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Improved functional abilities of the life-extended Drosophila mutant Methuselah are reversed at old age to below control levels

Petrosyan

Gonçalves

Hsieh

et al. 2013

AGE

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Methuselah (mth) is a chromosome 3 Drosophila mutant with an increased lifespan. A large number of studies have investigated the genetic, molecular, and biochemical mechanisms of the mth gene. Much less is known about the effects of mth on preservation of sensorimotor abilities throughout Drosophila's lifespan, particularly in late life. The current study investigated functional senescence in mth and its parental-control line (w1118) in two experiments that measured age-dependent changes in flight functions and locomotor activity. In experiment 1, a total of 158 flies (81 mth and 77 controls) with an age range from 10 to 70 days were individually tethered under an infrared laser-sensor system that allowed monitoring of flight duration during phototaxic flight. We found that mth has a statistically significant advantage in maintaining continuous flight over control flies at age 10 days, but not during middle and late life. At age 70 days, the trend reversed and parental control flies had a small but significant advantage, suggesting an interaction between age and genotype in the ability to sustain flight. In experiment 2, a total of 173 different flies (97 mth and 76 controls) with an age range from 50 to 76 days were individually placed in a large well-lit arena (60×45 cm) and their locomotor activity quantified as the distance walked in a 1-min period. Results showed that mth flies had lower levels of locomotor activity relative to controls at ages 50 and 60 days. These levels converged for the two genotypes at the oldest ages tested. Findings show markedly different patterns of functional decline for the mth line relative to those previously reported for other life-extended genotypes, suggesting that different life-extending genes have dissimilar effects on preservation of sensory and motor abilities throughout an organism's lifespan.

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“…Unlike Cat, the over expression of Sod-Cu/Zn in Drosophila increases the lifespan [30,31] proportionally to the activity of the enzyme. Moreover, the simultaneous expression of MnSod and Sod-Cu/Zn has an additive effect [32], whereas the simultaneous expression of the enzyme Mn-Sod and Cat does not provide additional benefits [33].…”

Section: Introductionmentioning

confidence: 99%

Action of protoporphyrin-IX (PP-IX) in the lifespan of <i>Drosophila melanogaster</i> deficient in endogenous antioxidants, Sod and Cat

Pimentel¹,

Vidal²,

Cruces³

et al. 2013

OJAS

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Protoporphyirin-IX (PP-IX) is a precursor of the biosynthesis of the hemo group, most of the cytochromes and the chlorophylls. The PP-IX is used for medical purposes, and recently a report indicated that it exhibits a dual action since it can decrease or increase the genetic damage caused by N-nitroso-N-ethylurea (ENU) in somatic cells of Drosophila. PP-IX is known to be able to act as an anti-or pro-oxidant agent. The aim of the present research was to study the role of PP-IX on the lifespan of Drosophila melanogaster, taking into account the fact that increasing levels of ROS can accelerate the aging process. The Canton-S strain (CS) was used as well as Sod and Cat which are deficient in the endogenous enzymes, superoxide dismutase and catalase, respectively. Groups of females and males were treated separately with 5 mg/ml of PP-IX solution. The comparison of survival curves indicates that this pigment extended the lifespan of CS. In contrast, Sod strain showed that the opposite effect and had no effect in Cat strain. The fact that PP-IX reduces the mean lifespan in Sod deficient strain might suggest a pro-oxidant action of PP-IX, and consequently the cumulating of ROS as a superoxide could have a mutagenic effect as was shown recently. The results presented evidence of the dual effect of PP-IX.

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Targeted neuronal gene expression and longevity in Drosophila

Cited by 65 publications

References 23 publications

Estrogen, Insulin, and Dietary Signals Cooperatively Regulate Longevity Signals to Enhance Resistance to Oxidative Stress in Mice

Estrogen, Insulin, and Dietary Signals Cooperatively Regulate Longevity Signals to Enhance Resistance to Oxidative Stress in Mice

Improved functional abilities of the life-extended Drosophila mutant Methuselah are reversed at old age to below control levels

Action of protoporphyrin-IX (PP-IX) in the lifespan of <i>Drosophila melanogaster</i> deficient in endogenous antioxidants, Sod and Cat

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Targeted neuronal gene expression and longevity in Drosophila

Cited by 65 publications

References 23 publications

Estrogen, Insulin, and Dietary Signals Cooperatively Regulate Longevity Signals to Enhance Resistance to Oxidative Stress in Mice

Estrogen, Insulin, and Dietary Signals Cooperatively Regulate Longevity Signals to Enhance Resistance to Oxidative Stress in Mice

Improved functional abilities of the life-extended Drosophila mutant Methuselah are reversed at old age to below control levels

Action of protoporphyrin-IX (PP-IX) in the lifespan of &lt;i&gt;Drosophila melanogaster&lt;/i&gt; deficient in endogenous antioxidants, Sod and Cat

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Action of protoporphyrin-IX (PP-IX) in the lifespan of <i>Drosophila melanogaster</i> deficient in endogenous antioxidants, Sod and Cat