Redox-based flagging of the global network of oxidative stress greatly promotes longevity

Donatella Canistro, Caterina Boccia, Rosanna Falconi, Barbara Bonamassa, Luca Valgimigli, Fabio Vivarelli, Antonio Soleti, Maria Luisa Genova, Giorgio Lenaz, Andrea Sapone, Francesco Zaccanti, Sherif Z. Abdel-Rahman, Moreno Paolini

    Research output: Contribution to journalArticlepeer-review

    15 Scopus citations

    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 OSâ€"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.

    Original languageEnglish (US)
    Pages (from-to)936-943
    Number of pages8
    JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
    Volume70
    Issue number8
    DOIs
    StatePublished - Aug 2015

    Keywords

    • Longevity
    • Oxidative stress

    ASJC Scopus subject areas

    • Aging
    • Geriatrics and Gerontology

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