Geroprotective Potential of Genetic and Pharmacological Interventions to Endogenous Hydrogen Sulfide Synthesis in Drosophila Melanogaster

Overview

Journal Biogerontology

Specialty Geriatrics

Date 2021 Feb 5

PMID 33544267

Citations 2

Authors

Mikhail V Shaposhnikov

Nadezhda V Zemskaya

Liubov A Koval

Eugenia V Schegoleva

Daria V Yakovleva

Natalia S Ulyasheva

Anastasia A Gorbunova

Natalya R Minnikhanova

Alexey A Moskalev

Affiliations

Soon will be listed here.

Abstract

Endogenous hydrogen sulfide (HS) is a gasotransmitter with a wide range of physiological functions. Aging is accompanied by disruption of HS homeostasis, therefore, interventions to the processes of HS metabolism to maintain its balance may have geroprotective potential. Here we demonstrated the additive geroprotective effect of combined genetic and pharmacological interventions to the hydrogen sulfide biosynthesis system by overexpression of cystathionine-β-synthase and cystathionine-γ-lyase genes and treatment with precursors of HS synthesis cysteine (Cys) and N-acetyl-L-cysteine (NAC). The obtained results suggest that additive effects of genetic and pharmacological interventions to HS metabolism may be associated with the complex interaction between beneficial action of HS production and prevention of adverse effects of excess HS production by Cys and NAC treatment.

Citing Articles

Simultaneous activation of the hydrogen sulfide biosynthesis genes (CBS and CSE) induces sex-specific geroprotective effects in Drosophila melanogaster.

Shaposhnikov M, Gorbunova A, Zemskaya N, Ulyasheva N, Pakshina N, Yakovleva D Biogerontology. 2023; 24(2):275-292.

PMID: 36662374 DOI: 10.1007/s10522-023-10017-2.

Molecular mechanisms of exceptional lifespan increase of Drosophila melanogaster with different genotypes after combinations of pro-longevity interventions.

Shaposhnikov M, Guvatova Z, Zemskaya N, Koval L, Schegoleva E, Gorbunova A Commun Biol. 2022; 5(1):566.

PMID: 35681084 PMC: 9184560. DOI: 10.1038/s42003-022-03524-4.

References

Admasu T, Batchu K, Barardo D, Ng L, Lam V, Xiao L . Drug Synergy Slows Aging and Improves Healthspan through IGF and SREBP Lipid Signaling. Dev Cell. 2018; 47(1):67-79.e5. DOI: 10.1016/j.devcel.2018.09.001. View

Austad S, Bartke A . Sex Differences in Longevity and in Responses to Anti-Aging Interventions: A Mini-Review. Gerontology. 2015; 62(1):40-6. DOI: 10.1159/000381472. View

Avanesian A, Khodayari B, Felgner J, Jafari M . Lamotrigine extends lifespan but compromises health span in Drosophila melanogaster. Biogerontology. 2009; 11(1):45-52. PMC: 2797622. DOI: 10.1007/s10522-009-9227-1. View

Barardo D, Thornton D, Thoppil H, Walsh M, Sharifi S, Ferreira S . The DrugAge database of aging-related drugs. Aging Cell. 2017; 16(3):594-597. PMC: 5418190. DOI: 10.1111/acel.12585. View

Baskar R, Li L, Moore P . Hydrogen sulfide-induces DNA damage and changes in apoptotic gene expression in human lung fibroblast cells. FASEB J. 2006; 21(1):247-55. DOI: 10.1096/fj.06-6255com. View

Beauchamp Jr R, Bus J, Popp J, Boreiko C, Andjelkovich D . A critical review of the literature on hydrogen sulfide toxicity. Crit Rev Toxicol. 1984; 13(1):25-97. DOI: 10.3109/10408448409029321. View

Brack C, Labuhn M . N-acetylcysteine slows down ageing and increases the life span of Drosophila melanogaster. Cell Mol Life Sci. 1998; 53(11-12):960-6. PMC: 11147307. DOI: 10.1007/pl00013199. View

Budde M, Roth M . Hydrogen sulfide increases hypoxia-inducible factor-1 activity independently of von Hippel-Lindau tumor suppressor-1 in C. elegans. Mol Biol Cell. 2009; 21(1):212-7. PMC: 2801715. DOI: 10.1091/mbc.e09-03-0199. View

Budde M, Roth M . The response of Caenorhabditis elegans to hydrogen sulfide and hydrogen cyanide. Genetics. 2011; 189(2):521-32. PMC: 3189795. DOI: 10.1534/genetics.111.129841. View

10.

Castillo-Quan J, Tain L, Kinghorn K, Li L, Gronke S, Hinze Y . A triple drug combination targeting components of the nutrient-sensing network maximizes longevity. Proc Natl Acad Sci U S A. 2019; 116(42):20817-20819. PMC: 6800352. DOI: 10.1073/pnas.1913212116. View

11.

Chen C, Xin H, Zhu Y . Hydrogen sulfide: third gaseous transmitter, but with great pharmacological potential. Acta Pharmacol Sin. 2007; 28(11):1709-16. DOI: 10.1111/j.1745-7254.2007.00629.x. View

12.

Chen X, Zhao X, Lan F, Zhou T, Cai H, Sun H . Hydrogen Sulphide Treatment Increases Insulin Sensitivity and Improves Oxidant Metabolism through the CaMKKbeta-AMPK Pathway in PA-Induced IR C2C12 Cells. Sci Rep. 2017; 7(1):13248. PMC: 5643337. DOI: 10.1038/s41598-017-13251-0. View

13.

de Cabo R, Diaz-Ruiz A . A Central Role for the Gasotransmitter HS in Aging. Cell Metab. 2020; 31(1):10-12. DOI: 10.1016/j.cmet.2019.11.015. View

14.

de Magalhaes J, Toussaint O . GenAge: a genomic and proteomic network map of human ageing. FEBS Lett. 2004; 571(1-3):243-7. DOI: 10.1016/j.febslet.2004.07.006. View

15.

Desjardins D, Cacho-Valadez B, Liu J, Wang Y, Yee C, Bernard K . Antioxidants reveal an inverted U-shaped dose-response relationship between reactive oxygen species levels and the rate of aging in Caenorhabditis elegans. Aging Cell. 2016; 16(1):104-112. PMC: 5242296. DOI: 10.1111/acel.12528. View

16.

DiNicolantonio J, OKeefe J, McCarty M . Boosting endogenous production of vasoprotective hydrogen sulfide via supplementation with taurine and N-acetylcysteine: a novel way to promote cardiovascular health. Open Heart. 2017; 4(1):e000600. PMC: 5471864. DOI: 10.1136/openhrt-2017-000600. View

17.

Doka E, Ida T, Dagnell M, Abiko Y, Luong N, Balog N . Control of protein function through oxidation and reduction of persulfidated states. Sci Adv. 2020; 6(1):eaax8358. PMC: 6938701. DOI: 10.1126/sciadv.aax8358. View

18.

Dombkowski R, Russell M, Schulman A, Doellman M, Olson K . Vertebrate phylogeny of hydrogen sulfide vasoactivity. Am J Physiol Regul Integr Comp Physiol. 2004; 288(1):R243-52. DOI: 10.1152/ajpregu.00324.2004. View

19.

Edwards C, Canfield J, Copes N, Brito A, Rehan M, Lipps D . Mechanisms of amino acid-mediated lifespan extension in Caenorhabditis elegans. BMC Genet. 2015; 16:8. PMC: 4328591. DOI: 10.1186/s12863-015-0167-2. View

20.

Fabrizio P, Pozza F, Pletcher S, Gendron C, Longo V . Regulation of longevity and stress resistance by Sch9 in yeast. Science. 2001; 292(5515):288-90. DOI: 10.1126/science.1059497. View