Involvement of Redox State in the Aging of<i>Drosophila melanogaster</i>

Orr, William C.; Radyuk, Svetlana N.; Sohal, Rajindar S.

doi:10.1089/ars.2012.5002

Cited by 46 publications

(54 citation statements)

References 130 publications

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“…suggested to play a role in aging and age-related disorders. [30][31][32][33] It is, therefore, purported that the enhancement of antioxidant enzymes such as SOD, which converts superoxide to H 2 O 2 , and catalase, which converts H 2 O 2 to water and oxygen, may attenuate age-related oxidative damage, thus resulting in the extension of life span. 34.35 We investigated the ability of GTP to enhance these antioxidant enzymes.…”

Section: Figmentioning

confidence: 99%

Green Tea Polyphenols Extend the Lifespan of MaleDrosophila melanogasterWhile Impairing Reproductive Fitness

Lopez

Schriner

Okoro

et al. 2014

Journal of Medicinal Food

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Green tea is a popular beverage believed to have many health benefits, including a reduction in the risks of heart disease and cancer. Rich in polyphenolic compounds known as catechins, green tea and its components have been shown to increase the lifespan of various animal models, including Drosophila melanogaster. Here, we investigated the genderspecific effects of green tea on the lifespan of fruit flies and observed that green tea extended the lifespan of male flies only. This effect was found to be independent of typical aging interventions, such as dietary restriction, modulation of oxidative energy metabolism, and improved tolerance to environmental stresses. The one exception was that green tea did protect male flies against iron toxicity. Since there is an inverse correlation between lifespan and reproduction, the impact of green tea on male reproductive fitness was also investigated. We found that green tea negatively impacted male fertility as shown by a reduced number of offspring produced and increased mating latency. We further identified that the lifespan extension properties of green tea was only observed in the presence of females which alludes to a reproductive (or mating) dependent mechanism. Our findings suggest that green tea extends the lifespan of male flies by inhibiting reproductive potential, possibly by limiting iron uptake. To our knowledge, our study is the first to report the negative impact of green tea on Drosophila male reproduction. Our results also support previous studies that suggest that green tea might have a negative effect on reproductive fitness in humans.

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Section: Figmentioning

confidence: 99%

Green Tea Polyphenols Extend the Lifespan of MaleDrosophila melanogasterWhile Impairing Reproductive Fitness

Lopez

Schriner

Okoro

et al. 2014

Journal of Medicinal Food

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“…This theory has been questioned recently due mainly to the failure of antioxidant therapies to extend aging and to the existence of organisms like the naked mole rat which have low levels of antioxidants and high levels of oxidative damage but nevertheless live seven times longer than the domestic mouse [reviewed in (Scialo et al 2013)]. At physiological levels, it is now admitted that ROS signal information through oxidation of specific sulfhydryl groups on key signaling proteins (Genova and Lenaz 2015;Orr et al 2013;Wang et al 2012). However there is a threshold above which ROS become harmful and induce oxidative stress (Dai et al 2014;Genova and Lenaz 2015;Orr et al 2013;Rigoulet et al 2011).…”

Section: Introductionmentioning

confidence: 99%

“…At physiological levels, it is now admitted that ROS signal information through oxidation of specific sulfhydryl groups on key signaling proteins (Genova and Lenaz 2015;Orr et al 2013;Wang et al 2012). However there is a threshold above which ROS become harmful and induce oxidative stress (Dai et al 2014;Genova and Lenaz 2015;Orr et al 2013;Rigoulet et al 2011). Mitochondria are the main generators of ROS, and complex I is considered as the major source of ROS involved in aging (Barja 2014;Genova and Lenaz 2015;Holzerova and Prokisch 2015;Orr et al 2013;Scialo et al 2013).…”

Section: Introductionmentioning

confidence: 99%

“…However there is a threshold above which ROS become harmful and induce oxidative stress (Dai et al 2014;Genova and Lenaz 2015;Orr et al 2013;Rigoulet et al 2011). Mitochondria are the main generators of ROS, and complex I is considered as the major source of ROS involved in aging (Barja 2014;Genova and Lenaz 2015;Holzerova and Prokisch 2015;Orr et al 2013;Scialo et al 2013). Indeed, longlived animals have species-specific low mitochondrial ROS generation rates at complex I, and the extension of longevity by caloric restriction can be mimicked by inhibition of this ETC complex [reviewed in (Barja 2014;Genova and Lenaz 2015;Schmeisser 2011, 2014;Scialo et al 2013)].…”

Section: Introductionmentioning

confidence: 99%

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Drosophila melanogaster mitochondrial Hsp22: a role in resistance to oxidative stress, aging and the mitochondrial unfolding protein response

2015

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Aging is characterized by the accumulation of dysfunctional mitochondria. Since these organelles are involved in many important cellular processes, different mechanisms exist to maintain their integrity. Among them is the mitochondrial unfolding protein response, which triggers the expression of a set of proteins aimed at re-establishing mitochondrial homeostasis. The induction of mitochondrial chaperones expression, particularly of Hsp60 and Hsp70, is a hallmark of this pathway. In Drosophila melanogaster, Hsp22 is also up-regulated by mitochondrial stress. This small heat shock protein is one of the members of the family to be localized inside mitochondria. One characteristic of Drosophila Hsp22 is its preferential up-regulation during aging and in oxidative stress conditions. It is a beneficial protein since its over-expression increases lifespan and resistance to stress while its down-regulation is detrimental. This review focuses on Drosophila Hsp22 and its links with the mitochondrial unfolding protein response and the aging process, in addition to highlight the important role of this sHSP in mitochondrial homeostasis.

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“…In Drosophila, hydrogen peroxide production significantly increases during aging (Cochemé et al ., 2011; Sohal & Orr, 2012; Orr et al ., 2013) and increased ROS release during aging was observed from rodent muscles, heart, liver, and brain (Sohal et al ., 1994; Bejma & Ji, 1999; Bejma et al ., 2000; Driver et al ., 2000; Vasilaki et al ., 2006; reviewed in Hekimi et al ., 2011). …”

Section: Testing Predictions Of This Modelmentioning

confidence: 99%

Evidence that a mitochondrial death spiral underlies antagonistic pleiotropy

Stern

2017

Aging Cell

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SummaryThe antagonistic pleiotropy (AP) theory posits that aging occurs because alleles that are detrimental in older organisms are beneficial to growth early in life and thus are maintained in populations. Although genes of the insulin signaling pathway likely participate in AP, the insulin‐regulated cellular correlates of AP have not been identified. The mitochondrial quality control process called mitochondrial autophagy (mitophagy), which is inhibited by insulin signaling, might represent a cellular correlate of AP. In this view, rapidly growing cells are limited by ATP production; these cells thus actively inhibit mitophagy to maximize mitochondrial ATP production and compete successfully for scarce nutrients. This process maximizes early growth and reproduction, but by permitting the persistence of damaged mitochondria with mitochondrial DNA mutations, becomes detrimental in the longer term. I suggest that as mitochondrial ATP output drops, cells respond by further inhibiting mitophagy, leading to a further decrease in ATP output in a classic death spiral. I suggest that this increasing ATP deficit is communicated by progressive increases in mitochondrial ROS generation, which signals inhibition of mitophagy via ROS‐dependent activation of insulin signaling. This hypothesis clarifies a role for ROS in aging, explains why insulin signaling inhibits autophagy, and why cells become progressively more oxidized during aging with increased levels of insulin signaling and decreased levels of autophagy. I suggest that the mitochondrial death spiral is not an error in cell physiology but rather a rational approach to the problem of enabling successful growth and reproduction in a competitive world of scarce nutrients.

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Involvement of Redox State in the Aging ofDrosophila melanogaster

Cited by 46 publications

References 130 publications

Green Tea Polyphenols Extend the Lifespan of MaleDrosophila melanogasterWhile Impairing Reproductive Fitness

Green Tea Polyphenols Extend the Lifespan of MaleDrosophila melanogasterWhile Impairing Reproductive Fitness

Drosophila melanogaster mitochondrial Hsp22: a role in resistance to oxidative stress, aging and the mitochondrial unfolding protein response

Evidence that a mitochondrial death spiral underlies antagonistic pleiotropy

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