title: Long-Lived αMUPA Mice Show Reduced Sexual Dimorphism in Lifespan, and in Energy and Circadian Homeostasis-Related Parameters.
abstract: Female αMUPA (alpha murine urokinase-like plasminogen activator) transgenic mice show increased lifespan, reduced body weight and food intake, and high-amplitude circadian rhythms with an endogenous period length (tau) of 24h, versus their wild types (WT) showing a 23.7-h tau. Our goal was to characterize αMUPA and WT male mice, and their in-strain sexual dimorphism, and to further understand the mechanisms underlying αMUPA's longevity. Male αMUPA mice showed increased lifespan, reduced body weight and food intake, and aligned endogenous rhythm with a tau of 24.0h versus a tau <24h in WT. However, no differences were found when intake was corrected for metabolic mass in male αMUPA mice. αMUPA's sexual dimorphism was damped or lacking in all studied traits, while WTs were sexually dimorphic, concluding that αMUPA's transgene overrides sex-dependent mechanisms involved in lifespan and in energy and circadian homeostasis. As enhanced resonance between tau and external circadian cycle correlates with increased lifespan and reduced body weight in other species, including humans, αMUPA's 24-h tau could contribute to their longevity. Focusing future research on the mechanistic interconnections between energy homeostasis, circadian homeostasis, sexual dimorphism, and aging, using αMUPA mice, may reveal mechanisms promoting reduced body weight and increased lifespan.
authors: Unit of Integrative Physiology (LIP), Laboratory of Human Health and Nutrition Sciences, MIGAL - Galilee Research Institute, Kiryat Shmona, Israel. Department of Nutritional Sciences, Tel-Hai College, Upper Galilee, Israel.
authors: Rafi
authors: R
authors: Steckler
authors: Unit of Integrative Physiology (LIP), Laboratory of Human Health and Nutrition Sciences, MIGAL - Galilee Research Institute, Kiryat Shmona, Israel.
authors: Ateret
authors: A
authors: Shabtay-Yanai
authors: Unit of Integrative Physiology (LIP), Laboratory of Human Health and Nutrition Sciences, MIGAL - Galilee Research Institute, Kiryat Shmona, Israel. Department of Nutritional Sciences, Tel-Hai College, Upper Galilee, Israel.
authors: Mariel
authors: M
authors: Pinsky
authors: Unit of Integrative Physiology (LIP), Laboratory of Human Health and Nutrition Sciences, MIGAL - Galilee Research Institute, Kiryat Shmona, Israel.
authors: Maayan
authors: M
authors: Rauch
authors: Department of Nutritional Sciences, Tel-Hai College, Upper Galilee, Israel. Laboratory of Human Health and Nutrition Sciences, MIGAL - Galilee Research Institute, Kiryat Shmona, Israel.
authors: Snait
authors: S
authors: Tamir
authors: Unit of Integrative Physiology (LIP), Laboratory of Human Health and Nutrition Sciences, MIGAL - Galilee Research Institute, Kiryat Shmona, Israel. Department of Nutritional Sciences, Tel-Hai College, Upper Galilee, Israel. Department of Animal Science, Faculty of Sciences and Technology, Tel-Hai College, Upper Galilee, Israel. roeeg@migal.org.il.
authors: Roee
authors: R
authors: Gutman
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001835:Body Weight / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D006706:Homeostasis / Q000502:physiology*; D008124:Locomotion / Q000502:physiology; D008136:Longevity / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D012727:Sex Characteristics
keywords: Circadian rhythms; Locomotor activity.; Longevity; Sexual dimorphism; αMUPA (Alpha Murine Urokinase-like Plasminogen Activator)