Geroprotective potential of genetic and pharmacological interventions to endogenous hydrogen sulfide synthesis in Drosophila melanogaster

Shaposhnikov, Mikhail; Zemskaya, Nadezhda; Koval, Liubov; Schegoleva, Eugenia V.; Yakovleva, Daria; Ulyasheva, Natalia S.; Gorbunova, Anastasia A.; Minnikhanova, Natalya R; Moskalev, Alexey

doi:10.1007/s10522-021-09911-4

Cited by 8 publications

(4 citation statements)

References 96 publications

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“…Looking at hydrogen sulfide (HSO) homeostasis, Alexey Moskalev, Russian academy of Sciences, Russia, has found that its disruption is associated with aging and therefore a potential gero-therapeutic target. He showed that combined genetic and therapeutic interventions of HSO metabolism led to beneficial effects of HSO production and life-and health span extension in D. melanogaster along with stress resistance [14]. Another novel mechanism to regulate homeostasis at the embryonic level is through adrenal steroidogenesis.…”

Section: Longevity Pathwaysmentioning

confidence: 99%

Meeting Report: Aging Research and Drug Discovery

Meron

Thaysen

Angeli

et al. 2022

Aging

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Aging is the single largest risk factor for most chronic diseases, and thus possesses large socioeconomic interest to continuously aging societies. Consequently, the field of aging research is expanding alongside a growing focus from the industry and investors in aging research. This year's 8th Annual Aging Research and Drug Discovery (ARDD) meeting was organized as a hybrid meeting from August 30th to September 3rd 2021 with more than 130 attendees participating on-site at the Ceremonial Hall at University of Copenhagen, Denmark, and 1800 engaging online. The conference comprised of presentations from 75 speakers focusing on new research in topics including mechanisms of aging and how these can be modulated as well as the use of AI and new standards of practices within aging research. This year, a longevity workshop was included to build stronger connections with the clinical community.

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Section: Longevity Pathwaysmentioning

confidence: 99%

Meeting Report: Aging Research and Drug Discovery

Meron

Thaysen

Angeli

et al. 2022

Aging

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“…Анализ выживаемости. Оценку выживаемости и статистическую обработку данных выполняли по методике, описанной ранее [15,16]. Эксперимент проводили в трех независимых биологических повторностях.…”

Section: материалы и методыunclassified

Effect of selective drugs that modulate the response to DNA damage on the radioresistance of Drosophila melanogaster

Ulyasheva

Proshkina²,

Shaposhnikov³

et al. 2022

Proceedings of the Komi Science Centre of the Ural Division of the Russian Academy of Sciences

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The search for drugs that affect the radioresistance of an organism is an urgent task of radiobiology and medicine. The effects of retinoic acid, enoxacin, KN-93, and UNC-0646 on resistance to γ-irradiation at doses of 120 and 800 Gy, as well as on the level of DNA damage and the efficiency of DNA repair were studied for the first time using the Drosophila melanogaster model. The results of the study indicate an increase in the radiosensitivity of flies after the addition of all four selective drugs to the medium at a young and mature age. Median and maximum survival after substance treatment was reduced to 50% (p < 0.0001). In addition, KN-93 and UNC-0646 exacerbated radioinduced DNA damage in males, but resulted in a moderate protective effect in females. At the same time, a protective effect of enoxacin against DNA damage was found in males. The influence of the studied drugs on the survival of Drosophila can be associated with the period of use of pharmacological compounds, the amount of their intake into an organism of males and females, the selected doses and irradiation regimens.

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“…4,23 Boosting endogenous H 2 S level is able to prolong lifespan in several model organisms, including yeast, flies, worms, and mice. 5,[24][25][26][27] It is widely reported that H 2 S exerts its biological activities through the S-sulfhydration modification of active cysteine residues, thus blocking irreversible oxidation and altering the functions of target proteins. [28][29][30][31] The global S-sulfhydrated proteins (sulfhydrome) have been shown to be disrupted in aging tissues from mice.…”

Section: Introductionmentioning

confidence: 99%

“…H 2 S mediates the beneficial effect of caloric restriction in promoting longevity 4,23 . Boosting endogenous H 2 S level is able to prolong lifespan in several model organisms, including yeast, flies, worms, and mice 5,24‐27 . It is widely reported that H 2 S exerts its biological activities through the S ‐sulfhydration modification of active cysteine residues, thus blocking irreversible oxidation and altering the functions of target proteins 28‐31 .…”

Section: Introductionmentioning

confidence: 99%

Cystathionine gamma‐lyase/H₂S signaling facilitates myogenesis under aging and injury condition

et al. 2021

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Hydrogen sulfide (H 2 S) can be endogenously produced and belongs to the class of signaling molecules known as gasotransmitters. Cystathionine gamma-lyase (CSE)-derived H 2 S is implicated in the regulation of cell differentiation and the aging process, but the involvements of the CSE/H 2 S system in myogenesis upon aging and injury have not been explored. In this study, we demonstrated that CSE acts as a major H 2 S-generating enzyme in skeletal muscles and is significantly downregulated in aged skeletal muscles in mice. CSE deficiency exacerbated the agedependent sarcopenia and cardiotoxin-induced injury/regeneration in mouse skeletal muscle, possibly attributed to inefficient myogenesis. In contrast, supplement of NaHS (an H 2 S donor) induced the expressions of myogenic genes and promoted muscle regeneration in mice. In vitro, incubation of myoblast cells (C2C12) with H 2 S promoted myogenesis, as evidenced by the inhibition of cell cycle progression and migration, altered expressions of myogenic markers, elongation of myoblasts, and formation of multinucleated myotubes. Myogenesis was also found to upregulate CSE expression, while blockage of CSE/H 2 S signaling resulted in a suppression of myogenesis. Mechanically, H 2 S significantly induced the heterodimer formation between MEF2c and MRF4 and promoted the binding of MEF2c/MRF4 to myogenin promoter. MEF2c was S-sulfhydrated at both cysteine 361 and 420 in the C-terminal transactivation domain, and blockage of MEF2c S-sulfhydration abolished the stimulatory role of H 2 S on MEF2c/MRF4 heterodimer formation. These findings support an essential role for H 2 S in maintaining myogenesis, presenting it as a potential candidate for the prevention of age-related sarcopenia and treatment of muscle injury.

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Geroprotective potential of genetic and pharmacological interventions to endogenous hydrogen sulfide synthesis in Drosophila melanogaster

Cited by 8 publications

References 96 publications

Meeting Report: Aging Research and Drug Discovery

Meeting Report: Aging Research and Drug Discovery

Effect of selective drugs that modulate the response to DNA damage on the radioresistance of Drosophila melanogaster

Cystathionine gamma‐lyase/H₂S signaling facilitates myogenesis under aging and injury condition

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Geroprotective potential of genetic and pharmacological interventions to endogenous hydrogen sulfide synthesis in Drosophila melanogaster

Cited by 8 publications

References 96 publications

Meeting Report: Aging Research and Drug Discovery

Meeting Report: Aging Research and Drug Discovery

Effect of selective drugs that modulate the response to DNA damage on the radioresistance of Drosophila melanogaster

Cystathionine gamma‐lyase/H2S signaling facilitates myogenesis under aging and injury condition

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Cystathionine gamma‐lyase/H₂S signaling facilitates myogenesis under aging and injury condition