Basic mechanisms of longevity: A case study of Drosophila pro-longevity genes

Proshkina, Ekaterina; Shaposhnikov, Mikhail; Садритдинова, А. Ф.; Kudryavtseva, Anna V.; Moskalev, Alexey

doi:10.1016/j.arr.2015.08.005

Cited by 32 publications

(19 citation statements)

References 132 publications

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“…In many cases, neuronal expression of genes also extends lifespan, as is seen in the case of dMPPED [69]. Overexpression of proteins important in DNA and protein repair, proteolysis, antioxidant activity, and autophagic processes also extend lifespan and include dSir2, dFOXO [30], hSOD [74] and…”

Section: Discussionmentioning

confidence: 98%

“…dMPPED is a pro-longevity gene, which reduces lifespan upon loss-of-function and extends lifespan when overexpressed. A number of genes have been shown to extend lifespan on overexpression in the fly [69] and include dTsc1 and dTsc2 (orthologs of tuberous sclerosis complex genes) [70]; dPTEN (phosphatase and tensin homolog) [30]; genes encoding enzymes involved in energy homeostasis such as d-NAAM (nicotinamide amidase) [71], men (malic enzyme) [72], and zw (homolog of G6PDH) [73].…”

Section: Discussionmentioning

confidence: 99%

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An evolutionarily conserved metallophosphodiesterase is a determinant of lifespan inDrosophila

Gupta

Janardan

Banerjee

et al. 2020

Preprint

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Evolutionarily conserved genes usually have a critical role to play during organismal aging and longevity. Here, we show that a previously uncharacterized Class III metallophosphoesterase in Drosophila, an ortholog of the MPPED1 and MPPED2 proteins in mammals, is necessary for optimal lifespan. dMPPED is the product of the gene CG16717 and hydrolyzed a variety of phosphodiester substrates in a metal-dependent manner. dMPPED was expressed widely during development and in the adult fly. Deletion of the gene in flies dramatically reduced lifespan, without affecting development or fecundity. Longevity was restored on ubiquitous expression of the protein, and neuronal expression of both wild type and the catalytically inactive form of dMPPED was also able to restore normal lifespan. Overexpression of the protein, both ubiquitously and neuronally in wild type flies extended lifespan by ~ 20%. RNA-seq analysis of dMPPED KO flies revealed mis-regulation of innate immune pathways, a number of transcription factors and genes earlier reported to affect aging and lifespan.Importantly, neuronal expression of mammalian MPPED2 was able to rescue lifespan in dMPPED KO flies, but not extend lifespan in wild type flies. This reports the first description of the biological role of an evolutionarily conserved metallophosphoesterase that may serve as a scaffolding protein in diverse signaling pathways to modulate longevity in the fly.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

An evolutionarily conserved metallophosphodiesterase is a determinant of lifespan inDrosophila

Gupta

Janardan

Banerjee

et al. 2020

Preprint

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“…Действительно, 1) нам не известно ни одного гена, единственной функцией которого был бы контроль над продолжительностью жизни. Большинство известных генов, регулирующих продолжительность жизни, в первую очередь, участвуют в таких процессах, как репарация ДНК (включая репликацию теломер), ме-таболизм и т. д., которые и определяют общую стабиль-ность и устойчивость биологической системы (Kenyon et al, 1993;Ayyadevara et al, 2008;Garinis et al, 2008;Zane et al, 2014;Ivanov et al, 2015;Proshkina et al, 2015;Pan, Finkel, 2017;Van Raamsdonk, 2017); 2) нам не известно ни одного внешнего фактора, который бы напрямую регулировал исключительно продолжительность жизни. Так, например, диета влияет прежде всего на метаболизм и, следовательно, на продолжительность жизни.…”

Section: Test Systems and Biotests Vavilov Journal Of Genetics And Brunclassified

“…Так, мутации в ряде генов, контролирующих метаболизм, рост, упаковку ДНК в хроматин, репарацию ДНК и т. д., могут приво-дить к ощутимым изменениям в средней продолжитель-ности жизни (Kenyon et al, 1993;Ayyadevara et al, 2008;Garinis et al, 2008;Zane et al, 2014;Ivanov et al, 2015;Proshkina et al, 2015;Pan, Finkel, 2017;Van Raamsdonk, 2017). Очевидно, что генетика старения представляет собой обширную область исследований, и на данный момент уже известно порядка 900/200/100 генов (http:// genomics.senescence.info), отвечающих за увеличение или уменьшение продолжительности жизни, у нематод (Caenorhabditis elegans), мух (Drosophila melanogaster) и мышей (Mus musculus) соответственно (Tacutu et al, 2013).…”

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A link between phenotypic robustness and life expectancy in Drosophila melanogaster

Zakharenko¹,

Petrovskii²,

Дранов³

et al. 2017

Vestn. VOGiS

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Long-lived systems are expected to be stable, i. e. resistant to either external influences, or internal failures. Robustness of biological systems can be defined as a reciprocal value to their phenotypic plasticity expressed through a coefficient of variation (C.V.) for positively distributed phenotypic traits. Considering lifespan as phenotype, which integrates all functions of an organism, we showed that its phenotypic robustness correlates positively with life expectancy. We assessed lifespan parameters for a selection of inbred Drosophila melanogaster strains from Drosophila Genetic Reference Panel (DGRP) reared at 29 ºС. The robustness of lifespan phenotype (C.V.-1 ) correlated positively with estimated life expectancy for these strains. The same relation also holds for the lifespan of all DGRP strains reared at 25 ºС. Also, in agreement with previous observations, upon temperature change (decrease or increase) the survival curves scaled in time (stretched or shrunk respectively). In other words, the average lifespan decreased for flies reared at elevated temperature, but so did the standard deviation, and thus the coefficients of variation remained in the same range. From this we conclude that coefficients of variation correlate with life expectancies and account for the robustness of lifespan phenotype irrespective of accelerated aging caused by temperature.Key words: lifespan; life expectancy; aging; phenotypic plasticity; phenotypic robustness; Drosophila melanogaster.Любая долгоживущая система должна быть стабильной, т. е. обла-дать повышенной устойчивостью как к внешним воздействиям, так и к внутренним сбоям. Робастность биологических систем может быть определена как реципрокная величина к фенотипической изменчивости или, для положительно распределенных признаков, к коэффициенту вариации (C.V.). Рассматривая продолжительность жизни как интегральный фенотип всех функций организма, мы по-казали, что фенотипическая робастность организма положитель-но коррелирует с ожидаемой продолжительностью жизни. Мы определили параметры продолжительности жизни для ряда ин-бредных линий Drosophila melanogaster, выращенных при 29 ºС, из коллекции Drosophila Genetic Reference Panel (DGRP). Фенотипиче-ская робастность продолжительности жизни (C.V.-1 ) для этих линий коррелировала положительно с ожидаемой продолжительностью жизни. Соотношение между робастностью и ожидаемой продол-жительностью жизни сохраняется и для DGRP линий, выра щенных при 25 ºС. Помимо этого, в соответствии с ранее опубли кованными результатами, с изменением (уменьшением или увели чением) тем-пературы кривые дожития масштабируются (растягиваются или сжимаются соответственно) по временной шкале. Иными словами, с увеличением температуры падает как средняя продолжитель-ность жизни, так и стандартное отклонение от средней продолжи-тельности жизни, в то время как коэффициенты вариации сохра-няются в том же диапазоне. Исходя из этого, мы заключили, что коэффициенты вариации коррелируют со средней продолжитель-ностью жизни и отражают фенотипическую робастно...

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“…They have also been studied extensively over recent years for their potential in chemotherapy for parasitic diseases of humans, including malaria, toxoplasmosis, trypanosomiasis, schistosomiasis and leishamaniasis (Andrews et al., 2012a, Andrews et al., 2012b; Marek et al., 2015). HDAC enzymes have been studied extensively in the model dipteran insect Drosophila with respect to their roles in longevity and memory formation (Fitzsimons et al., 2013, Proshkina et al., 2015, Schwartz et al., 2016), with a Drosophila model providing experimental evidence to highlight HDACi as potential therapeutics for the treatment of Huntington's disease (Sharma and Taliyan, 2015). However, only a single study has reported the insecticidal activity of an HDACi against this fly species, with Pile et al.…”

Section: Introductionmentioning

confidence: 99%

Insecticidal activities of histone deacetylase inhibitors against a dipteran parasite of sheep, Lucilia cuprina

Bagnall

Hines

Lucke

et al. 2017

International Journal for Parasitology: Drugs and Drug Resistan

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Histone deacetylase inhibitors (HDACi) are being investigated for the control of various human parasites. Here we investigate their potential as insecticides for the control of a major ecto-parasite of sheep, the Australian sheep blowfly, Lucilia cuprina. We assessed the ability of HDACi from various chemical classes to inhibit the development of blowfly larvae in vitro, and to inhibit HDAC activity in nuclear protein extracts prepared from blowfly eggs. The HDACi prodrug romidepsin, a cyclic depsipeptide that forms a thiolate, was the most potent inhibitor of larval growth, with equivalent or greater potency than three commercial blowfly insecticides. Other HDACi with potent activity were hydroxamic acids (trichostatin, CUDC-907, AR-42), a thioester (KD5170), a disulphide (Psammaplin A), and a cyclic tetrapeptide bearing a ketone (apicidin). On the other hand, no insecticidal activity was observed for certain other hydroxamic acids, fatty acids, and the sesquiterpene lactone parthenolide. The structural diversity of the 31 hydroxamic acids examined here revealed some structural requirements for insecticidal activity; for example, among compounds with flexible linear zinc-binding extensions, greater potency was observed in the presence of branched capping groups that likely make multiple interactions with the blowfly HDAC enzymes. The insecticidal activity correlated with inhibition of HDAC activity in blowfly nuclear protein extracts, indicating that the toxicity was most likely due to inhibition of HDAC enzymes in the blowfly larvae. The inhibitor potencies against blowfly larvae are different from inhibition of human HDACs, suggesting some selectivity for human over blowfly HDACs, and a potential for developing compounds with the inverse selectivity. In summary, these novel findings support blowfly HDAC enzymes as new targets for blowfly control, and point to development of HDAC inhibitors as a promising new class of insecticides.

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Basic mechanisms of longevity: A case study of Drosophila pro-longevity genes

Cited by 32 publications

References 132 publications

An evolutionarily conserved metallophosphodiesterase is a determinant of lifespan inDrosophila

An evolutionarily conserved metallophosphodiesterase is a determinant of lifespan inDrosophila

A link between phenotypic robustness and life expectancy in Drosophila melanogaster

Insecticidal activities of histone deacetylase inhibitors against a dipteran parasite of sheep, Lucilia cuprina

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