Extended longevity and survivorship during amino-acid starvation in a Drosophila<i>Sir2</i>mutant heterozygote

Slade, Jennifer Denise; Staveley, Brian E.

doi:10.1139/gen-2015-0213

Cited by 14 publications

(10 citation statements)

References 44 publications

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“…In terms of starvation stress, prenatal starvation was initially reported to alter DNA methylation marks on the imprinted gene IGF2 and this change persisted throughout the human life-span 3 . Other studies also suggested that Sirtuin 1 ( Sirt1 ), a histone deacetylase, plays a role in responses to starvation stress in Drosophila 4 . However, except for Sirt1 , the epigenetic factors that are critical in responses to starvation stress have not yet been identified.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic regulation of starvation-induced autophagy in Drosophila by histone methyltransferase G9a

Shimaji

Tanaka

et al. 2017

Sci Rep

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Epigenetics is now emerging as a key regulation in response to various stresses. We herein identified the Drosophila histone methyltransferase G9a (dG9a) as a key factor to acquire tolerance to starvation stress. The depletion of dG9a led to high sensitivity to starvation stress in adult flies, while its overexpression induced starvation stress resistance. The catalytic domain of dG9a was not required for starvation stress resistance. dG9a plays no apparent role in tolerance to other stresses including heat and oxidative stresses. Metabolomic approaches were applied to investigate global changes in the metabolome due to the loss of dG9a during starvation stress. The results obtained indicated that dG9a plays an important role in maintaining energy reservoirs including amino acid, trehalose, glycogen, and triacylglycerol levels during starvation. Further investigations on the underlying mechanisms showed that the depletion of dG9a repressed starvation-induced autophagy by controlling the expression level of Atg8a, a critical gene for the progression of autophagy, in a different manner to that in cancer cells. These results indicate a positive role for dG9a in starvation-induced autophagy.

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Section: Introductionmentioning

confidence: 99%

Epigenetic regulation of starvation-induced autophagy in Drosophila by histone methyltransferase G9a

Shimaji

Tanaka

et al. 2017

Sci Rep

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“…Moreover, overexpression of Sir2 in the adult fat body is sufficient to extend the lifespan of male and female Drosophila [53]. Importantly, increased Sir2 expression and reduced insulin receptor signaling results in an increase in the activity of the transcription factor FOXO [69]. In fly neuronal cells, increased Dyrk1a activates Sir2 to regulate the deacetylation of FOXO, which potentiates FOXO-induced sNPF/NPY expression and in turn promotes food intake.…”

Section: Discussionmentioning

confidence: 99%

The activation of cardiac dSir2-related pathways mediates physical exercise resistance to heart aging in old Drosophila

Wen

Zheng

et al. 2019

Aging

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Cardiac aging is majorly characterized by increased diastolic dysfunction, lipid accumulation, oxidative stress, and contractility debility. The Sir2/Sirt1 gene overexpression delays cell aging and reduces obesity and oxidative stress. Exercise improves heart function and delays heart aging. However, it remains unclear whether exercise delaying heart aging is related to cardiac Sir2/Sirt1-related pathways. In this study, cardiac dSir2 overexpression or knockdown was regulated using the UAS/hand-Gal4 system in Drosophila. Flies underwent exercise interventions from 4 weeks to 5 weeks old. Results showed that either cardiac dSir2 overexpression or exercise remarkably increased the cardiac period, systolic interval, diastolic interval, fractional shortening, SOD activity, dSIR2 protein, Foxo, dSir2, Nmnat, and bmm expression levels in the aging flies; they also notably reduced the cardiac triacylglycerol level, malonaldehyde level, and the diastolic dysfunction index. Either cardiac dSir2 knockdown or aging had almost opposite effects on the heart as those of cardiac dSir2 overexpression. Therefore, we claim that cardiac dSir2 overexpression or knockdown delayed or promoted heart aging by reducing or increasing age-related oxidative stress, lipid accumulation, diastolic dysfunction, and contractility debility. The activation of cardiac dSir2/Foxo/SOD and dSir2/Foxo/bmm pathways may be two important molecular mechanisms through which exercise works against heart aging in Drosophila.

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“…The dSir2 gene, a well‐known longevity gene, is a homolog of human SIRT1 . The overexpression of this gene was shown to extend longevity in multiple organisms, including yeast, worms, and flies during conditions of adequate nutrition and during nutritional stress (Slade & Staveley, ). The mRNA expression of dSir2 increased in flies fed 1.0 and 2.0 mg/ml phlorizin ( p < 0.05).…”

Section: Discussionmentioning

confidence: 99%

Apple phlorizin attenuates oxidative stress inDrosophila melanogaster

et al. 2018

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Apple phlorizin has a lot of applications owing to its antioxidant and hepatoprotective properties. This study explored the antioxidant effects and life span‐prolonging activity of apple phlorizin in Drosophila melanogaster. Treatment with apple phlorizin was found to significantly extend the life span and ameliorate the age‐related decline of locomotor function. This life span‐extending activity was associated with the increased activity of superoxide dismutase, catalase, mRNA expression of glutamate–cysteine ligase catalytic subunit, cap‐n‐collar (cnc, homologue of mammalian Nrf2 gene), Keap1, and deacetylase sir2, as well as the downregulation of methuselah. Computational analysis suggested phlorizin could work as a Nrf2 activator and exert its biological activities by interfering with the Keap1 and Nrf2 binding. Therefore, it was concluded that the antioxidant and anti‐aging effects of phlorizin might, at least in part, be mediated through the cooperation with the endogenous stress defense system. Practical applications Phlorizin, from apple peel, has been used as a nutrient for over 100 years. To date, despite extensive research on phlorizin, a report on its effect on the antioxidant system in fruit flies is yet lacking. This report demonstrates that phlorizin can exert a protective effect on antioxidant issues and prolong life in fruit flies, which is valuable in the rational utilization of phlorizin in functional foods.

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Extended longevity and survivorship during amino-acid starvation in a DrosophilaSir2mutant heterozygote

Cited by 14 publications

References 44 publications

Epigenetic regulation of starvation-induced autophagy in Drosophila by histone methyltransferase G9a

Epigenetic regulation of starvation-induced autophagy in Drosophila by histone methyltransferase G9a

The activation of cardiac dSir2-related pathways mediates physical exercise resistance to heart aging in old Drosophila

Apple phlorizin attenuates oxidative stress inDrosophila melanogaster

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