{
    "abstract": "Reactive oxygen species (ROS) are highly reactive oxygen containing molecules that are generated by normal metabolism. While ROS can cause damage to the building blocks that make up cells, these molecules can also act as intracellular signals that promote longevity. The levels of ROS within the cell can be regulated by antioxidant enzymes, such as superoxide dismutase (SOD), which converts superoxide to hydrogen peroxide. Interestingly, our previous work has shown that disruption of the mitochondrial SOD gene sod-2 results in increased lifespan, suggesting that elevating levels of mitochondrial superoxide can promote longevity. To explore the molecular mechanisms involved, we determined the tissues in which disruption of sod-2 is necessary for lifespan extension and the tissues in which disruption of sod-2 is sufficient to extend lifespan. We found that tissue-specific restoration of SOD-2 expression in worms lacking SOD-2 could partially revert changes in fertility, embryonic lethality and resistance to stress, but did not inhibit the effects of sod-2 deletion on lifespan. Knocking down sod-2 expression using RNA interference specifically in the intestine, but not other tissues, was sufficient to extend longevity. Intestine-specific knockdown of sod-2 also increased resistance to heat stress while decreasing resistance to oxidative stress. Combined, these results indicate that disruption of sod-2 in neurons, intestine, germline, or muscle is not required for lifespan extension, but that decreasing sod-2 expression in just the intestine extends lifespan. This work defines the conditions required for disruption of mitochondrial superoxide dismutase to increase longevity.",
    "authors": [
        {
            "affiliation": "Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada; Metabolic Disorders and Complications Program, and Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.",
            "firstname": "Thomas",
            "initials": "T",
            "lastname": "Liontis"
        },
        {
            "affiliation": "Laboratory of Aging and Neurodegenerative Disease (LAND), Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA.",
            "firstname": "Megan M",
            "initials": "MM",
            "lastname": "Senchuk"
        },
        {
            "affiliation": "Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada; Metabolic Disorders and Complications Program, and Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.",
            "firstname": "Shusen",
            "initials": "S",
            "lastname": "Zhu"
        },
        {
            "affiliation": "Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada; Metabolic Disorders and Complications Program, and Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.",
            "firstname": "Suleima",
            "initials": "S",
            "lastname": "Jacob-Tomas"
        },
        {
            "affiliation": "Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada; Metabolic Disorders and Complications Program, and Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.",
            "firstname": "Ulrich",
            "initials": "U",
            "lastname": "Anglas"
        },
        {
            "affiliation": "Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada; Metabolic Disorders and Complications Program, and Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.",
            "firstname": "Annika",
            "initials": "A",
            "lastname": "Traa"
        },
        {
            "affiliation": "Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada; Metabolic Disorders and Complications Program, and Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.",
            "firstname": "Sonja K",
            "initials": "SK",
            "lastname": "Soo"
        },
        {
            "affiliation": "Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada; Metabolic Disorders and Complications Program, and Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; Laboratory of Aging and Neurodegenerative Disease (LAND), Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA; Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, Quebec, Canada. Electronic address: jeremy.vanraamsdonk@mcgill.ca.",
            "firstname": "Jeremy M",
            "initials": "JM",
            "lastname": "Van Raamsdonk"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2025 The Author(s). Published by Elsevier Inc. All rights reserved.",
    "doi": "10.1016/j.freeradbiomed.2025.01.032",
    "journal": "Free radical biology & medicine",
    "keywords": [
        "Aging",
        "C. elegans",
        "Genetics",
        "Mitochondria",
        "Reactive oxygen species",
        "Superoxide dismutase",
        "Tissue specificity"
    ],
    "methods": null,
    "publication_date": "2025-01-20",
    "pubmed_id": "39827921",
    "results": null,
    "title": "Intestine-specific disruption of mitochondrial superoxide dismutase extends longevity.",
    "xml": "<Element 'PubmedArticle' at 0x788505fc3ec0>"
}