title: Redox-Based Flagging of the Global Network of Oxidative Stress Greatly Promotes Longevity.
abstract: Despite more than 50 years of investigations into the free radical theory, the direct role of oxidative stress (OS) in aging and age-related diseases remains unproven. Little progress in identifying antioxidant drugs promoting longevity has been made, likely due to selectivity toward one or few radical species, variable efficacy in vivo, inherent pro-oxidant behavior of such drugs, or lack of synergism with metabolic redox homeostasis. Silencing the wide range of reactive free radicals has a great impact on OS-linked outcomes and age-related disorders. Here we show that an innovative, redox-active, multi-radical-scavenger catalytic drug delays the age-associated decline in physiological processes and markedly prolongs the mean lifespan of the adult freshwater annelids Aeolosoma viride by 170%. This unprecedented extension is associated with a decreased OS status. Consistently, treatment of annelids increases their natural resistance to oxygen-derived damage without affecting mitochondrial respiration or reproductive activity. Conversely, the superoxide dismutase (SOD)-mimetic EUK 134 that we selected as a positive control led to an increase in lifespan of ~50%, the same increase previously observed in nematodes. Our results show that reduction of the global network of OS has a profound impact on aging, prompting the development of a possible redox-based therapeutic intervention to counteract the progression of aging.
authors.affiliation: Department of Pharmacy and Biotechnology and donatella.canistro@unibo.it.
authors.forename: Donatella
authors.initials: D
authors.lastname: Canistro
authors.affiliation: Department of Biological, Geological and Environmental Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Boccia
authors.affiliation: Department of Biological, Geological and Environmental Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Falconi
authors.affiliation: Department of Pharmaceutical Sciences, University of Pittsburgh, Pennsylvania.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bonamassa
authors.affiliation: Department of Chemistry "G. Ciamician" and.
authors.forename: Luca
authors.initials: L
authors.lastname: Valgimigli
authors.affiliation: Department of Pharmacy and Biotechnology and.
authors.forename: Fabio
authors.initials: F
authors.lastname: Vivarelli
authors.affiliation: Department of Pharmacy and Biotechnology and.
authors.forename: Antonio
authors.initials: A
authors.lastname: Soleti
authors.affiliation: Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Genova
authors.affiliation: Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Lenaz
authors.affiliation: Department of Pharmacy and Biotechnology and.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sapone
authors.affiliation: Department of Biological, Geological and Environmental Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Zaccanti
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas.
authors.forename: Sherif Z
authors.initials: SZ
authors.lastname: Abdel-Rahman
authors.affiliation: Department of Pharmacy and Biotechnology and.
authors.forename: Moreno
authors.initials: M
authors.lastname: Paolini
mesh_terms: D000818:Animals; D000845:Annelida / Q000502:physiology*; D004578:Electron Spin Resonance Spectroscopy; D008136:Longevity; D009942:Organometallic Compounds / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D012459:Salicylates / Q000494:pharmacology
chemical_list: C433928:EUK-134; D009942:Organometallic Compounds; D012459:Salicylates
keywords: Longevity; Oxidative stress