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S-linolenoyl glutathione intake extends life-span and stress resistance via Sir-2.1 upregulation in Caenorhabditis elegans.
Free Radic Biol Med. 2014 Aug; 73:127-35.FR

Abstract

Oxidative stress has a prominent role in life-span regulation of living organisms. One of the endogenous free radical scavenger systems is associated with glutathione (GSH), the most abundant nonprotein thiol in mammalian cells, acting as a major reducing agent and in antioxidant defense by maintaining a tight control over redox status. We have recently designed a series of novel S-acyl-GSH derivatives capable of preventing amyloid oxidative stress and cholinergic dysfunction in Alzheimer disease models, upon an increase in GSH intake. In this study we show that the longevity of the wild-type N2 Caenorhabditis elegans strain was significantly enhanced by dietary supplementation with linolenoyl-SG (lin-SG) thioester with respect to the ethyl ester of GSH, linolenic acid, or vitamin E. RNA interference analysis and activity inhibition assay indicate that life-span extension was mediated by the upregulation of Sir-2.1, a NAD-dependent histone deacetylase ortholog of mammalian SIRT1. In particular, lin-SG-mediated overexpression of Sir-2.1 appears to be related to the Daf-16 (FoxO) pathway. Moreover, the lin-SG derivative protects N2 worms from the paralysis and oxidative stress induced by Aβ/H2O2 exposure. Overall, our findings put forward lin-SG thioester as an antioxidant supplement triggering sirtuin upregulation, thus opening new future perspectives for healthy aging or delayed onset of oxidative-related diseases.

Authors+Show Affiliations

Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy.Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy.Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy.Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy.Department of Chemistry "Ugo Schiff," University of Florence, 50019 Sesto Fiorentino, Florence, Italy.Department of Chemistry "Ugo Schiff," University of Florence, 50019 Sesto Fiorentino, Florence, Italy.Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy.Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy.Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy. Electronic address: cristina.cecchi@unifi.it.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24835770

Citation

Cascella, Roberta, et al. "S-linolenoyl Glutathione Intake Extends Life-span and Stress Resistance Via Sir-2.1 Upregulation in Caenorhabditis Elegans." Free Radical Biology & Medicine, vol. 73, 2014, pp. 127-35.
Cascella R, Evangelisti E, Zampagni M, et al. S-linolenoyl glutathione intake extends life-span and stress resistance via Sir-2.1 upregulation in Caenorhabditis elegans. Free Radic Biol Med. 2014;73:127-35.
Cascella, R., Evangelisti, E., Zampagni, M., Becatti, M., D'Adamio, G., Goti, A., Liguri, G., Fiorillo, C., & Cecchi, C. (2014). S-linolenoyl glutathione intake extends life-span and stress resistance via Sir-2.1 upregulation in Caenorhabditis elegans. Free Radical Biology & Medicine, 73, 127-35. https://doi.org/10.1016/j.freeradbiomed.2014.05.004
Cascella R, et al. S-linolenoyl Glutathione Intake Extends Life-span and Stress Resistance Via Sir-2.1 Upregulation in Caenorhabditis Elegans. Free Radic Biol Med. 2014;73:127-35. PubMed PMID: 24835770.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - S-linolenoyl glutathione intake extends life-span and stress resistance via Sir-2.1 upregulation in Caenorhabditis elegans. AU - Cascella,Roberta, AU - Evangelisti,Elisa, AU - Zampagni,Mariagioia, AU - Becatti,Matteo, AU - D'Adamio,Giampiero, AU - Goti,Andrea, AU - Liguri,Gianfranco, AU - Fiorillo,Claudia, AU - Cecchi,Cristina, Y1 - 2014/05/15/ PY - 2013/11/28/received PY - 2014/04/18/revised PY - 2014/05/09/accepted PY - 2014/5/20/entrez PY - 2014/5/20/pubmed PY - 2015/5/12/medline KW - C. elegans KW - Daf-16 (FoxO) KW - Free radicals KW - Glutathione KW - Longevity KW - Oxidative stress KW - Sir-2.1 SP - 127 EP - 35 JF - Free radical biology & medicine JO - Free Radic. Biol. Med. VL - 73 N2 - Oxidative stress has a prominent role in life-span regulation of living organisms. One of the endogenous free radical scavenger systems is associated with glutathione (GSH), the most abundant nonprotein thiol in mammalian cells, acting as a major reducing agent and in antioxidant defense by maintaining a tight control over redox status. We have recently designed a series of novel S-acyl-GSH derivatives capable of preventing amyloid oxidative stress and cholinergic dysfunction in Alzheimer disease models, upon an increase in GSH intake. In this study we show that the longevity of the wild-type N2 Caenorhabditis elegans strain was significantly enhanced by dietary supplementation with linolenoyl-SG (lin-SG) thioester with respect to the ethyl ester of GSH, linolenic acid, or vitamin E. RNA interference analysis and activity inhibition assay indicate that life-span extension was mediated by the upregulation of Sir-2.1, a NAD-dependent histone deacetylase ortholog of mammalian SIRT1. In particular, lin-SG-mediated overexpression of Sir-2.1 appears to be related to the Daf-16 (FoxO) pathway. Moreover, the lin-SG derivative protects N2 worms from the paralysis and oxidative stress induced by Aβ/H2O2 exposure. Overall, our findings put forward lin-SG thioester as an antioxidant supplement triggering sirtuin upregulation, thus opening new future perspectives for healthy aging or delayed onset of oxidative-related diseases. SN - 1873-4596 UR - https://www.unboundmedicine.com/medline/citation/24835770/S_linolenoyl_glutathione_intake_extends_life_span_and_stress_resistance_via_Sir_2_1_upregulation_in_Caenorhabditis_elegans_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(14)00220-2 DB - PRIME DP - Unbound Medicine ER -