Abstract
Endogenous hydrogen sulfide (H2S) is a gasotransmitter with a wide range of physiological functions. Aging is accompanied by disruption of H2S homeostasis, therefore, interventions to the processes of H2S 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 H2S synthesis cysteine (Cys) and N-acetyl-l-cysteine (NAC). The obtained results suggest that additive effects of genetic and pharmacological interventions to H2S metabolism may be associated with the complex interaction between beneficial action of H2S production and prevention of adverse effects of excess H2S production by Cys and NAC treatment.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Admasu TD et al (2018) Drug synergy slows aging and improves healthspan through IGF and SREBP lipid signaling. Dev Cell 47:67–79. https://doi.org/10.1016/j.devcel.2018.09.001
Albertini E, Koziel R, Durr A, Neuhaus M, Jansen-Durr P (2012) Cystathionine beta synthase modulates senescence of human endothelial cells. Aging (Albany NY) 4:664–673
Arvidsson S, Kwasniewski M, Riaño-Pachón DM, Mueller-Roeber B (2008) QuantPrime—a flexible tool for reliable high-throughput primer design for quantitative PCR. BMC Bioinf 9:465. https://doi.org/10.1186/1471-2105-9-465
Austad SN, Bartke A (2015) Sex differences in longevity and in responses to anti-aging interventions: a mini-review. Gerontology 62:40–46. https://doi.org/10.1159/000381472
Avanesian A, Khodayari B, Felgner JS, Jafari M (2010) Lamotrigine extends lifespan but compromises health span in Drosophila melanogaster. Biogerontology 11:45–52. https://doi.org/10.1007/s10522-009-9227-1
Barardo D et al (2017) The DrugAge database of aging-related drugs. Aging Cell 16:594–597. https://doi.org/10.1111/acel.12585
Baskar R, Li L, Moore PK (2007) Hydrogen sulfide-induces DNA damage and changes in apoptotic gene expression in human lung fibroblast cells. FASEB J 21:247–255. https://doi.org/10.1096/fj.06-6255com
Beauchamp RO Jr, Bus JS, Popp JA, Boreiko CJ, Andjelkovich DA (1984) A critical review of the literature on hydrogen sulfide toxicity. Crit Rev Toxicol 13:25–97. https://doi.org/10.3109/10408448409029321
Brack C, Bechter-Thüring E, Labuhn M (1997) N-Acetylcysteine slows down ageing and increases the life span of Drosophila melanogaster. Cell Mol Life Sci 53:960–966. https://doi.org/10.1007/pl00013199
Budde MW, Roth MB (2010) Hydrogen sulfide increases hypoxia-inducible factor-1 activity independently of von Hippel-Lindau tumor suppressor-1 in C. elegans. Mol Biol Cell 21:212–217. https://doi.org/10.1091/mbc.E09-03-0199
Budde MW, Roth MB (2011) The response of Caenorhabditis elegans to hydrogen sulfide and hydrogen cyanide. Genetics 189:521–532. https://doi.org/10.1534/genetics.111.129841
Castillo-Quan JI et al (2019) A triple drug combination targeting components of the nutrient-sensing network maximizes longevity. Proc Natl Acad Sci USA 116:20817–20819. https://doi.org/10.1073/pnas.1913212116
Chen CQ, Xin H, Zhu YZ (2007) Hydrogen sulfide: third gaseous transmitter, but with great pharmacological potential. Acta Pharmacol Sin 28:1709–1716. https://doi.org/10.1111/j.1745-7254.2007.00629.x
Chen X et al (2017) Hydrogen sulphide treatment increases insulin sensitivity and improves oxidant metabolism through the CaMKKbeta-AMPK pathway in PA-induced IR C2C12 cells. Sci Rep 7:13248. https://doi.org/10.1038/s41598-017-13251-0
Danilov A, Shaposhnikov M, Plyusnina E, Kogan V, Fedichev P, Moskalev A (2013) Selective anticancer agents suppress aging in Drosophila. Oncotarget 4:1507–1526
de Cabo R, Diaz-Ruiz A (2020) A central role for the gasotransmitter H2S in aging. Cell Metab 31:10–12. https://doi.org/10.1016/j.cmet.2019.11.015
de Magalhães JP, Toussaint O (2004) GenAge: a genomic and proteomic network map of human ageing. FEBS Lett 571:243–247. https://doi.org/10.1016/j.febslet.2004.07.006
Desjardins D et al (2017) Antioxidants reveal an inverted U-shaped dose-response relationship between reactive oxygen species levels and the rate of aging in Caenorhabditis elegans. Aging Cell 16:104–112. https://doi.org/10.1111/acel.12528
DiNicolantonio JJ, OKeefe JH, McCarty MF (2017) Boosting endogenous production of vasoprotective hydrogen sulfide via supplementation with taurine and N-acetylcysteine: a novel way to promote cardiovascular health. Open Heart 4:e000600. https://doi.org/10.1136/openhrt-2017-000600
Dóka É et al (2020) Control of protein function through oxidation and reduction of persulfidated states. Sci Adv 6:eaax8358. https://doi.org/10.1126/sciadv.aax8358
Dombkowski RA, Russell MJ, Schulman AA, Doellman MM, Olson KR (2005) Vertebrate phylogeny of hydrogen sulfide vasoactivity. Am J Physiol Regul Integr Comp Physiol 288:R243-252. https://doi.org/10.1152/ajpregu.00324.2004
Du Y, Liu XH, Zhu HC, Wang L, Wang ZS, Ning JZ, Xiao CC (2019) Hydrogen sulfide treatment protects against renal ischemia-reperfusion injury via induction of heat shock proteins in rats. Iranian J Basic Med Sci 22:99–105
Edwards C et al (2015) Mechanisms of amino acid-mediated lifespan extension in Caenorhabditis elegans. BMC Genet 16:8. https://doi.org/10.1186/s12863-015-0167-2
Ezeriņa D, Takano Y, Hanaoka K, Urano Y, Dick TP (2018) N-acetyl cysteine functions as a fast-acting antioxidant by triggering intracellular H2S and sulfane sulfur production. Cell Chem Biol 25(447–459):e444. https://doi.org/10.1016/j.chembiol.2018.01.011
Fabrizio P, Pozza F, Pletcher SD, Gendron CM, Longo VD (2001) Regulation of longevity and stress resistance by Sch9 in yeast. Science 292:288–290. https://doi.org/10.1126/science.1059497
Filipovic MR, Zivanovic J, Alvarez B, Banerjee R (2018) Chemical biology of H2S signaling through persulfidation. Chem Rev 118:1253–1337. https://doi.org/10.1021/acs.chemrev.7b00205
Flurkey K, Astle CM, Harrison DE (2010) Life extension by diet restriction and N-acetyl-L-cysteine in genetically heterogeneous mice. J Gerontol A Biol Sci Med Sci 65:1275–1284. https://doi.org/10.1093/gerona/glq155
Fu L, Liu K, He J, Tian C, Yu X, Yang J (2020) Direct proteomic mapping of cysteine persulfidation. Antioxid Redox Signal 33:1061–1076. https://doi.org/10.1089/ars.2019.7777
Gaitanidis A, Dimitriadou A, Dowse H, Sanyal S, Duch C, Consoulas C (2019) Longitudinal assessment of health-span and pre-death morbidity in wild type Drosophila. Aging (Albany NY) 11:1850–1873
Garratt M (2020) Why do sexes differ in lifespan extension? Sex-specific pathways of aging and underlying mechanisms for dimorphic responses. Nutr Healthy Aging 5:247–259. https://doi.org/10.3233/NHA-190067
Grotewiel MS, Martin I, Bhandari P, Cook-Wiens E (2005) Functional senescence in Drosophila melanogaster. Ageing Res Rev 4:372–397. https://doi.org/10.1016/j.arr.2005.04.001
Han SK et al (2016) OASIS 2: online application for survival analysis 2 with features for the analysis of maximal lifespan and healthspan in aging research. Oncotarget 7:56147–56152
Hine C et al (2015) Endogenous hydrogen sulfide production is essential for dietary restriction benefits. Cell 160:132–144. https://doi.org/10.1016/j.cell.2014.11.048
Ibrahim H, Serag A, Farag MA (2021) Emerging analytical tools for the detection of the third gasotransmitter H2S, a comprehensive review. J Adv Res 27:137–153. https://doi.org/10.1016/j.jare.2020.05.018
Jain SK, Huning L, Micinski D (2014) Hydrogen sulfide upregulates glutamate-cysteine ligase catalytic subunit, glutamate-cysteine ligase modifier subunit, and glutathione and inhibits interleukin-1β secretion in monocytes exposed to high glucose levels. Metab Syndr Relat Disord 12:299–302. https://doi.org/10.1089/met.2014.0022
Janssens GE, Houtkooper RH (2020) Identification of longevity compounds with minimized probabilities of side effects. Biogerontology 21:709–719. https://doi.org/10.1007/s10522-020-09887-7
Johnson TE, de Castro E, Hegi de Castro S, Cypser J, Henderson S, Tedesco P (2001) Relationship between increased longevity and stress resistance as assessed through gerontogene mutations in Caenorhabditis elegans. Exp Gerontol 36:1609–1617. https://doi.org/10.1016/S0531-5565(01)00144-9
Kabil H, Kabil O, Banerjee R, Harshman LG, Pletcher SD (2011) Increased transsulfuration mediates longevity and dietary restriction in Drosophila. Proc Natl Acad Sci USA 108:16831–16836. https://doi.org/10.1073/pnas.1102008108
Kabil O, Banerjee R (2014) Enzymology of H2S biogenesis, decay and signaling. Antioxid Redox Signal 20:770–782. https://doi.org/10.1089/ars.2013.5339
Ke X et al (2017) Heat shock protein 90/Akt pathway participates in the cardioprotective effect of exogenous hydrogen sulfide against high glucose-induced injury to H9c2 cells. Int J Mol Med 39:1001–1010. https://doi.org/10.3892/ijmm.2017.2891
Kennedy BK et al (2014) Geroscience: linking aging to chronic disease. Cell 159:709–713. https://doi.org/10.1016/j.cell.2014.10.039
Kimura H (2020) Signalling by hydrogen sulfide and polysulfides via protein S-sulfuration. Br J Pharmacol 177:720–733. https://doi.org/10.1111/bph.14579
Landis GN, Doherty D, Tower J (2020) Analysis of Drosophila melanogaster lifespan. Methods Mol Biol 2144:47–56. https://doi.org/10.1007/978-1-0716-0592-9_4
Liu D et al (2014) Hydrogen sulfide promotes proliferation and neuronal differentiation of neural stem cells and protects hypoxia-induced decrease in hippocampal neurogenesis. Pharmacol Biochem Behav 116:55–63. https://doi.org/10.1016/j.pbb.2013.11.009
Longchamp A et al (2018) Amino acid restriction triggers angiogenesis via GCN2/ATF4 regulation of VEGF and H2S production. Cell 173(117–129):e114. https://doi.org/10.1016/j.cell.2018.03.001
Longen S, Beck KF, Pfeilschifter J (2016a) H2S-induced thiol-based redox switches: biochemistry and functional relevance for inflammatory diseases. Pharmacol Res 111:642–651. https://doi.org/10.1016/j.phrs.2016.07.026
Longen S, Richter F, Kohler Y, Wittig I, Beck KF, Pfeilschifter J (2016b) Quantitative persulfide site identification (qPerS-SID) reveals protein targets of H2S releasing donors in mammalian. Cells Sci Rep 6:29808. https://doi.org/10.1038/srep29808
Longo VD (2003) The Ras and Sch9 pathways regulate stress resistance and longevity. Exp Gerontol 38:807–811. https://doi.org/10.1016/S0531-5565(03)00113-X
Mantel N (1966) Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50:163–170
Mathew ND, Schlipalius DI, Ebert PR (2011) Sulfurous gases as biological messengers and toxins: comparative genetics of their metabolism in model organisms. J Toxicol 2011:394970. https://doi.org/10.1155/2011/394970
McBean GJ (2012) The transsulfuration pathway: a source of cysteine for glutathione in astrocytes. Amino Acids 42:199–205. https://doi.org/10.1007/s00726-011-0864-8
Mehta CR, Patel NR, Tsiatis AA (1984) Exact significance testing to establish treatment equivalence with ordered categorical data. Biometrics 40:819–825
Miller DL, Budde MW, Roth MB (2011) HIF-1 and SKN-1 coordinate the transcriptional response to hydrogen sulfide in Caenorhabditis elegans. PLoS ONE 6:e25476. https://doi.org/10.1371/journal.pone.0025476
Miller DL, Roth MB (2007) Hydrogen sulfide increases thermotolerance and lifespan in Caenorhabditis elegans. Proc Natl Acad Sci USA 104:20618–20622. https://doi.org/10.1073/pnas.0710191104
Módis K, Coletta C, Erdélyi K, Papapetropoulos A, Szabo C (2013a) Intramitochondrial hydrogen sulfide production by 3-mercaptopyruvate sulfurtransferase maintains mitochondrial electron flow and supports cellular bioenergetics. FASEB J 27:601–611. https://doi.org/10.1096/fj.12-216507
Módis K, Wolanska K, Vozdek R (2013b) Hydrogen sulfide in cell signaling, signal transduction, cellular bioenergetics and physiology in C. elegans. Gen Physiol Biophys 32:1–22. https://doi.org/10.4149/gpb_2013001
Mokhtari V, Afsharian P, Shahhoseini M, Kalantar SM, Moini A (2017) A review on various uses of N-acetyl cysteine. Cell J 19:11–17
Moskalev A (2020) Is anti-ageing drug discovery becoming a reality? Expert Opin Drug Discov 15:135–138. https://doi.org/10.1080/17460441.2020.1702965
Moskalev A et al (2015a) Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease. Aging (Albany NY) 7:616–628
Moskalev A et al (2015b) Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease. Aging 7:616–628
Moskalev A, Chernyagina E, Kudryavtseva A, Shaposhnikov M (2017) Geroprotectors: a unified concept and screening approaches. Aging Dis 8:354–363
Moskalev A et al (2016) Developing criteria for evaluation of geroprotectors as a key stage toward translation to the clinic. Aging Cell 15:407–415. https://doi.org/10.1111/acel.12463
Mun J, Kang HM, Jung J, Park C (2019) Role of hydrogen sulfide in cerebrovascular alteration during aging. Arch Pharm Res 42:446–454. https://doi.org/10.1007/s12272-019-01135-y
Ng LT, Ng LF, Tang RMY, Barardo D, Halliwell B, Moore PK, Gruber J (2020) Lifespan and healthspan benefits of exogenous H2S in C. elegans are independent from effects downstream of eat-2 mutation. NPJ Aging Mech Dis 6:6. https://doi.org/10.1038/s41514-020-0044-8
Oh SI, Park JK, Park SK (2015) Lifespan extension and increased resistance to environmental stressors by N-acetyl-L-cysteine in Caenorhabditis elegans. Clinics (Sao Paulo) 70:380–386. https://doi.org/10.6061/clinics/2015(05)13
Panthi S, Chung HJ, Jung J, Jeong NY (2016) Physiological importance of hydrogen sulfide: emerging potent neuroprotector and neuromodulator. Oxid Med Cell Longev 2016:9049782. https://doi.org/10.1155/2016/9049782
Paul BD, Snyder SH, Kashfi K (2021) Effects of hydrogen sulfide on mitochondrial function and cellular bioenergetics. Redox Biol 38:101772. https://doi.org/10.1016/j.redox.2020.101772
Perez VI, Bokov A, Van Remmen H, Mele J, Ran Q, Ikeno Y, Richardson A (2009) Is the oxidative stress theory of aging dead? Biochim Biophys Acta 1790:1005–1014. https://doi.org/10.1016/j.bbagen.2009.06.003
Perridon BW, Leuvenink HG, Hillebrands JL, van Goor H, Bos EM (2016) The role of hydrogen sulfide in aging and age-related pathologies. Aging (Albany NY) 8:2264–2289
Powolny AA, Singh SV, Melov S, Hubbard A, Fisher AL (2011) The garlic constituent diallyl trisulfide increases the lifespan of C. elegans via skn-1 activation. Exp Gerontol 46:441–452. https://doi.org/10.1016/j.exger.2011.01.005
Predmore BL, Alendy MJ, Ahmed KI, Leeuwenburgh C, Julian D (2010) The hydrogen sulfide signaling system: changes during aging and the benefits of caloric restriction. Age (Dordr) 32:467–481. https://doi.org/10.1007/s11357-010-9150-z
Pushpakumar S, Kundu S, Sen U (2014) Endothelial dysfunction: the link between homocysteine and hydrogen sulfide. Curr Med Chem 21:3662–3672. https://doi.org/10.2174/0929867321666140706142335
Qabazard B, Ahmed S, Li L, Arlt VM, Moore PK, Stürzenbaum SR (2013) C. elegans aging is modulated by hydrogen sulfide and the sulfhydrylase/cysteine synthase cysl-2. PLoS ONE 8:e80135. https://doi.org/10.1371/journal.pone.0080135
Qabazard B et al (2014) Hydrogen sulfide is an endogenous regulator of aging in Caenorhabditis elegans. Antioxid Redox Signal 20:2621–2630. https://doi.org/10.1089/ars.2013.5448
Sen N (2017) Functional and molecular insights of hydrogen sulfide signaling and protein sulfhydration. J Mol Biol 429:543–561. https://doi.org/10.1016/j.jmb.2016.12.015
Shaposhnikov M, Proshkina E, Koval L, Zemskaya N, Zhavoronkov A, Moskalev A (2018a) Overexpression of CBS and CSE genes affects lifespan, stress resistance and locomotor activity in Drosophila melanogaster. Aging (Albany NY) 10:3260–3272
Shaposhnikov MV, Zemskaya NV, Koval LA, Schegoleva EV, Zhavoronkov A, Moskalev AA (2018b) Effects of N-acetyl-l-cysteine on lifespan, locomotor activity and stress-resistance of 3 Drosophila species with different lifespans. Aging (Albany NY) 10:2428–2458
Shilova V, Zatsepina O, Zakluta A, Karpov D, Chuvakova L, Garbuz D, Evgen’ev M (2020) Age-dependent expression profiles of two adaptogenic systems and thermotolerance in Drosophila melanogaster. Cell Stress Chaperon 25:305–315. https://doi.org/10.1007/s12192-020-01074-4
Singh S, Padovani D, Leslie RA, Chiku T, Banerjee R (2009) Relative contributions of cystathionine beta-synthase and gamma-cystathionase to H2S biogenesis via alternative trans-sulfuration reactions. J Biol Chem 284:22457–22466. https://doi.org/10.1074/jbc.M109.010868
Smith JE 3rd, Cronmiller C (2001) The Drosophila daughterless gene autoregulates and is controlled by both positive and negative cis regulation. Development 128:4705–4714
Snijder PM et al (2016) Overexpression of cystathionine gamma-lyase suppresses detrimental effects of spinocerebellar ataxia type 3. Mol Med 21:758–768. https://doi.org/10.2119/molmed.2015.00221
Sun HJ, Wu ZY, Nie XW, Bian JS (2019) Role of endothelial dysfunction in cardiovascular diseases: the link between inflammation and hydrogen sulfide. Front Pharmacol 10:1568. https://doi.org/10.3389/fphar.2019.01568
Tabassum R, Jeong NY, Jung J (2020) Therapeutic importance of hydrogen sulfide in age-associated neurodegenerative diseases. Neural Regen Res 15:653–662. https://doi.org/10.4103/1673-5374.266911
Testai L, Citi V, Martelli A, Brogi S, Calderone V (2020) Role of hydrogen sulfide in cardiovascular ageing. Pharmacol Res 160:105125. https://doi.org/10.1016/j.phrs.2020.105125
Tower J (2017) Sex-specific gene expression and life span regulation. Trends Endocrinol Metab 28:735–747. https://doi.org/10.1016/j.tem.2017.07.002
Vaiserman AM, Lushchak OV, Koliada AK (2016) Anti-aging pharmacology: promises and pitfalls. Ageing Res Rev 31:9–35. https://doi.org/10.1016/j.arr.2016.08.004
Van Voorhies WA, Curtsinger JW, Rose MR (2006) Do longevity mutants always show trade-offs? Exp Gerontol 41:1055–1058. https://doi.org/10.1016/j.exger.2006.05.006
Viscomi C et al (2010) Combined treatment with oral metronidazole and N-acetylcysteine is effective in ethylmalonic encephalopathy. Nat Med 16:869–871. https://doi.org/10.1038/nm.2188
Wang C, Li Q, Redden DT, Weindruch R, Allison DB (2004) Statistical methods for testing effects on “maximum lifespan.” Mech Ageing Dev 125:629–632. https://doi.org/10.1016/j.mad.2004.07.003
Wang R (2002) Two’s company, three’s a crowd: can H2S be the third endogenous gaseous transmitter? FASEB J 16:1792–1798. https://doi.org/10.1096/fj.02-0211hyp
Wodarz A, Hinz U, Engelbert M, Knust E (1995) Expression of crumbs confers apical character on plasma membrane domains of ectodermal epithelia of Drosophila. Cell 82:67–76
Wong R, Piper MD, Wertheim B, Partridge L (2009) Quantification of food intake in Drosophila. PLoS ONE 4:e6063. https://doi.org/10.1371/journal.pone.0006063
Wu D, Si W, Wang M, Lv S, Ji A, Li Y (2015) Hydrogen sulfide in cancer: friend or foe? Nitric Oxide 50:38–45. https://doi.org/10.1016/j.niox.2015.08.004
Wu D, Wang H, Teng T, Duan S, Ji A, Li Y (2018) Hydrogen sulfide and autophagy: a double edged sword. Pharmacol Res 131:120–127. https://doi.org/10.1016/j.phrs.2018.03.002
Xin D et al (2018) l-Cysteine suppresses hypoxia-ischemia injury in neonatal mice by reducing glial activation, promoting autophagic flux and mediating synaptic modification via H2S formation. Brain Behav Immun 73:222–234. https://doi.org/10.1016/j.bbi.2018.05.007
Yang G et al (2013) Hydrogen sulfide protects against cellular senescence via S-sulfhydration of Keap1 and activation of Nrf2. Antioxid Redox Signal 18:1906–1919. https://doi.org/10.1089/ars.2012.4645
Yang Q, He GW (2019) Imbalance of homocysteine and H2S: significance, mechanisms, and therapeutic promise in vascular injury. Oxid Med Cell Longev 2019:7629673. https://doi.org/10.1155/2019/7629673
Zatsepina O et al (2020) Genome-wide transcriptional effects of deletions of sulphur metabolism genes in Drosophila melanogaster. Redox Biol 36:101654. https://doi.org/10.1016/j.redox.2020.101654
Zhang Y, Tang ZH, Ren Z, Qu SL, Liu MH, Liu LS, Jiang ZS (2013) Hydrogen sulfide, the next potent preventive and therapeutic agent in aging and age-associated diseases. Mol Cell Biol 33:1104–1113. https://doi.org/10.1128/MCB.01215-12
Zivanovic J et al (2019) Selective persulfide detection reveals evolutionarily conserved antiaging effects of S-sulfhydration. Cell Metab 30(1152–1170):e1113. https://doi.org/10.1016/j.cmet.2019.10.007
Acknowledgments
We are grateful to the Institute of Biology of Komi Science Center for assistance in the experiments with Drosophila and MIPT for assistance in data analysis.
Funding
This work was supported by the Russian Science Foundation Grant N 17-74-30030.
Author information
Authors and Affiliations
Contributions
Conceptualization, AAM and MVS; Methodology, MVS, NVZ and LAK; Software, MVS, NVZ and LAK; Investigation, NVZ, LAK, EVS, DVY, AAG, NSU and NRM; Data Curation, MVS, NVZ, LAK and EVS; Writing—Original Draft Preparation, MVS and NVZ; Writing—Review & Editing, AAM; Visualization, MVS and NVZ; Supervision, AAM; Project Administration, MVS; Funding Acquisition, AAM.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Shaposhnikov, M.V., Zemskaya, N.V., Koval, L.A. et al. Geroprotective potential of genetic and pharmacological interventions to endogenous hydrogen sulfide synthesis in Drosophila melanogaster. Biogerontology 22, 197–214 (2021). https://doi.org/10.1007/s10522-021-09911-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10522-021-09911-4