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The Road to a Long Lifespan in the Persian Squirrel, a Natural Model for Extended Longevity: Resisting Free Radical Stress and Healthy Phospholipids Publisher Pubmed



Salehi F1 ; Kavoosi G2 ; Jacobs PJ3 ; Bennett NC3 ; Ahmadian S1 ; Bastani B4 ; Gholami M5
Authors
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Authors Affiliations
  1. 1. Institute of Biochemistry and Biophysics, Department of Biochemistry, University of Tehran, Tehran, Iran
  2. 2. Institute of Biotechnology, Shiraz University, Shiraz, Iran
  3. 3. Department of Zoology and Entomology, Mammal Research Institute, University of Pretoria, Private Bag X20, Hatfield, Pretoria, 0028, South Africa
  4. 4. Bureau of Wildlife Management and Conservation, Deputy of Natural Environment and Biodiversity, Department of Environment, Tehran, Iran
  5. 5. Department of Toxicology & Pharmacology, Faculty of Pharmacy, Toxicology and Poisoning Research, Tehran University of Medical Sciences, Tehran, Iran

Source: GeroScience Published:2025


Abstract

Longevity is influenced by various factors, including fatty acid composition and free radical stress, which relate to the membrane pacemaker and rate of living hypotheses. While these aspects are well-documented in some long-lived species, they remain largely unexplored in tree squirrels. This study aimed to compare oxidative stress, antioxidant activity, nitrosative stress, and lipid composition between the long-lived Persian squirrel (Sciurus anomalus) and the short-lived Wistar rat across age cohorts (younger and older). Tissue homogenates from skin, liver, skeletal muscle, spleen, lung, and kidney were analysed for lipid composition (monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), arachidonic to linoleic acid ratio, peroxidation index, and unsaturation index. Oxidative, nitrosative, and antioxidant markers were assessed, including NADPH oxidase, superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase (GST), nitric oxide synthase, superoxide, hydrogen peroxide, nitric oxide, malondialdehyde, 4-hydroxynonenal, and total antioxidant capacity (TAC). Squirrels demonstrated higher GST activity, lower free radical stress, lower PUFA, and higher MUFA compared to rats. Antioxidant activities, except for TAC were negatively correlated with longevity. Older squirrels exhibited similar oxidative, nitrosative, and antioxidant profiles to younger squirrels, whereas younger rats displayed highly susceptible fatty acids, similar to older rats. The Persian squirrel’s longevity appears closely linked to fatty acid composition and free radical resistance, likely due to increased GST activity. We propose GST’s multifunctional role in reducing inflammation, enhancing immune response, providing disease resistance, and antioxidant activity contributes significantly to the longevity of the Persian squirrel. © The Author(s), under exclusive licence to American Aging Association 2025.
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