Genetic repression of the antioxidant enzymes reduces the lifespan in Drosophila melanogaster

Deepashree, S; Shivanandappa, T.; Ramesh, S. R.

doi:10.1007/s00360-021-01412-7

Cited by 13 publications

(7 citation statements)

References 64 publications

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“…These free radical species contribute to the pathophysiology of many neurodegenerative diseases, including amyloidosis, α-synucleinopathies, aging, and TDP-43 proteinopathies, which are caused by the inhibition of acetylcholinesterase [ 4 ]. Detoxification is aided by cellular defense mechanisms that involve endogenous antioxidants and antioxidant enzymes such as superoxide dismutase, glutathione reductase, lipid peroxidase, glutathione, and catalase [ 5 ]. The deterioration of these defense mechanisms damages significant cell biomolecules (lipids, DNA, and proteins) and ultimately leads to cell death [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Ethnopharmacological Effects of Urtica dioica, Matricaria chamomilla, and Murraya koenigii on Rotenone-Exposed D. melanogaster: An Attenuation of Cellular, Biochemical, and Organismal Markers

et al. 2022

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Natural antioxidants derived from plants have been proven to have significant inhibitory effects on the free radicals of living organisms during actively metabolization. Excessive production of free radicals increases the risk of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and motor sclerosis. This study aimed to compare the ethnopharmacological effects of Urtica dioica (UD), Matricaria chamomilla (MC), and Murraya koenigii (MK) on the amelioration of rotenone-induced toxicity in wild-type Drosophila melanogaster (Oregon R+) at biochemical, cellular, and behavioral levels. Phytoextracts were prepared from all three plants, i.e., UD, MC, and MK (aqueous and ethanolic fractions), and their bioactive compounds were evaluated using in vitro biochemical parameters (DPPH, ABTS, TPC, and TFC), UV-Vis, followed by FT-IR and HPLC. Third instar larvae and freshly eclosed flies were treated with 500 µM rotenone alone or in combination with UD, MC, and MK for 24 to 120 h. Following exposure, cytotoxicity (dye exclusion test), biochemical (protein estimation and acetylcholinesterase inhibition assays), and behavioral assays (climbing and jumping assays) were performed. Among all three plant extracts, MK exhibited the highest antioxidant properties due to the highest TPC, TFC, DPPH, and ABTS, followed by UD, then MC. The overall trend was MK > UD > MC. In this context, ethnopharmacological properties mimic the same effect in Drosophila, exhibiting significantly (p < 0.05) reduced cytotoxicity (trypan blue), improved biochemical parameters (proteotoxicity and AChE activity), and better behavioral parameters in the organisms cotreated with phyto extracts compared with rotenone. Conclusively, UV-Vis, FTIR, and HPLC analyses differentiated the plant extracts. The findings of this research may be beneficial in the use of select herbs as viable sources of phyto-ingredients that could be of interest in nutraceutical development and various clinical applications.

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Section: Introductionmentioning

confidence: 99%

Ethnopharmacological Effects of Urtica dioica, Matricaria chamomilla, and Murraya koenigii on Rotenone-Exposed D. melanogaster: An Attenuation of Cellular, Biochemical, and Organismal Markers

et al. 2022

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“…Enzymes are the third line of defense, which repairs or eliminates oxidative stress-induced damage to biomacromolecules (Yi et al, 2021). These endogenous antioxidant defenses play an important role in determining the lifespan of Drosophila (Deepashree et al, 2022). A previous study claimed that RJ abrogates cadmium-induced oxidative effects by elevating the Nrf2 mRNA levels in testes of mice (Almeer et al, 2018), but here we performed exhaustive genetic experiments to show that the antioxidant ability of RJ in flies is independent of Nrf2 signaling.…”

Section: Discussionmentioning

confidence: 91%

“…These endogenous antioxidant defenses play an important role in determining the lifespan of Drosophila (Deepashree et al. , 2022). A previous study claimed that RJ abrogates cadmium‐induced oxidative effects by elevating the Nrf2 mRNA levels in testes of mice (Almeer et al.…”

Section: Discussionmentioning

confidence: 99%

The endogenous antioxidant ability of royal jelly in Drosophila is independent of Keap1/Nrf2 by activating oxidoreductase activity

Wen,

Xie,

Yuan

et al. 2023

Insect Science

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Royal jelly (RJ) is a biologically active substance secreted by the hypopharyngeal and mandibular glands of worker honeybees. It is widely claimed that RJ reduces oxidative stress. However, the antioxidant activity of RJ has mostly been determined by in vitro chemical detection methods or by external administration drugs that cause oxidative stress. Whether RJ can clear the endogenous production of reactive oxygen species (ROS) in cells remains largely unknown. Here, we systematically investigated the antioxidant properties of RJ using several endogenous oxidative stress models of Drosophila. We found that RJ enhanced sleep quality of aging Drosophila, which is decreased due to an increase of oxidative damage with age. RJ supplementation improved survival and suppressed ROS levels in gut cells of flies upon exposure to hydrogen peroxide or to the neurotoxic agent paraquat. Moreover, RJ supplementation moderated levels of ROS in endogenous gut cells and extended lifespan after exposure of flies to heat stress. Sleep deprivation leads to accumulation of ROS in the gut cells, and RJ attenuated the consequences of oxidative stress caused by sleep loss and prolonged lifespan. Mechanistically, RJ prevented cell oxidative damage caused by heat stress or sleep deprivation, with the antioxidant activity in vivo independent of Keap1/Nrf2 signaling. RJ supplementation activated oxidoreductase activity in the guts of flies, suggesting its ability to inhibit endogenous oxidative stress and maintain health, possibly in humans.

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“…However, both in these previous studies and our current work, enhanced detoxification can be separated from longevity, suggesting the involvement of other protective mechanisms. Genetic suppression of the antioxidants superoxide dismutase or catalase severely compromises lifespan of flies, and similarly, pharmacologically inhibition of superoxide dismutase reduces the lifespan of longlived flies but not flies with a "normal" lifespan 35 . Conversely, overexpressing these antioxidants can extend lifespan 36 .…”

Section: Discussionmentioning

confidence: 99%

Short-term fasting of a single amino acid extends lifespan

Fulton,

Wansbrough,

Mirth

et al. 2023

Preprint

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Diet and health are strongly linked, though the strict changes in diet required to improve health outcomes are usually difficult to sustain. We sought to understand whether short term bouts of amino acid-specific modifications to the diet of Drosophila melanogaster could mimic the lifespan and stress resistance benefits of dietary restriction, without the requirement for drastic reductions in food intake. We found that flies fed diets lacking the essential amino acid isoleucine, but otherwise nutritionally complete, exhibited enhanced nicotine tolerance, indicating elevated detoxification capacity. The protection from isoleucine deprivation increased with the duration of exposure, up to a maximum at 7-day isoleucine deprivation for flies 2, 3, or 4 weeks of age, and a 5-day deprivation when flies were 5 weeks of age. Because of these beneficial effects on toxin resistance, we intermittently deprived flies of isoleucine during the first 6 weeks of adulthood and monitored the effect on lifespan. Lifespan was significantly extended when flies experienced short term isoleucine deprivation at 3 and 5 weeks of age, regardless of whether they were also deprived at 1 week. These results indicate that short-term bouts of isoleucine deprivation can extend lifespan and highlight its cumulative and time-dependent benefits. Interestingly, we found that isoleucine-deprived flies lost their protection against nicotine within three days of returning to fully fed conditions. Therefore, the mechanisms underlying lifespan extension may involve transient damage clearance during the bouts of isoleucine deprivation rather than sustained enhanced detoxification capacity. These data highlight a new time-restricted, nutritionally precise method to extend life in Drosophila melanogaster and point to a more manageable dietary method to combat ageing.

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Genetic repression of the antioxidant enzymes reduces the lifespan in Drosophila melanogaster

Cited by 13 publications

References 64 publications

Ethnopharmacological Effects of Urtica dioica, Matricaria chamomilla, and Murraya koenigii on Rotenone-Exposed D. melanogaster: An Attenuation of Cellular, Biochemical, and Organismal Markers

Ethnopharmacological Effects of Urtica dioica, Matricaria chamomilla, and Murraya koenigii on Rotenone-Exposed D. melanogaster: An Attenuation of Cellular, Biochemical, and Organismal Markers

The endogenous antioxidant ability of royal jelly in Drosophila is independent of Keap1/Nrf2 by activating oxidoreductase activity

Short-term fasting of a single amino acid extends lifespan

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