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The female survival advantage is a robust characteristic of human longevity. However, underlying mechanisms are not understood, and rodent models exhibiting a female advantage are lacking. Here, we report that the genetically heterogeneous (UM-HET3) mice used by the National Institute on Aging Interventions Testing Program (ITP) are such a model. Analysis of age-specific survival of 3,690 control ITP mice revealed a female survival advantage paralleling that of humans. As in humans, the female advantage in mice was greatest in early adulthood, peaking around 350 days of age and diminishing progressively thereafter. This persistent finding was observed at three geographically distinct sites and in six separate cohorts over a 10-year period. Because males weigh more than females and bodyweight is often inversely related to lifespan, we examined sex differences in the relationship between bodyweight and survival. Although present in both sexes, the inverse relationship between bodyweight and longevity was much stronger in males, indicating that male mortality is more influenced by bodyweight than is female mortality. In addition, male survival varied more across site and cohort than female survival, suggesting greater resistance of females to environmental modulators of survival. Notably, at 24 months the relationship between bodyweight and longevity shifted from negative to positive in both sexes, similar to the human condition in advanced age. These results indicate that the UM-HET3 mouse models the human female survival advantage and provide evidence for greater resilience of females to modulators of survival.
Pubmed ID: 30801953 RIS Download
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NIA''s ITP is a multi-institutional study investigating treatments with the potential to exte nd lifespan and delay disease and dysfunction in mice. Priority consideration will be given to the treatments that are easily obtainable, reasonably priced, and can be delivered in the diet (preferred) or water. Interventions that require labor intensive forms of administration, such as daily injections or gavage, are not feasible within the design of the ITP. Treatments currently under study include: - Pharmaceuticals - Nutraceuticals - Foods - Diets - Dietary supplements - Plant extracts - Hormones - Peptides - Amino acids - Chelators - Redox agents - Other agents or mixtures of agents Although the mice involved in this study will be housed at the University of Michigan, the Jackson Laboratories, and the University of Texas Health Sciences Center at San Antonio, the project is designed to involve collaborations with investigators at any university, institute, or other organization that has ideas about pharmacological interventions that might decelerate aging and wishes to test these in a lifespan study of mice. Sponsors: This program is supported by the National Institute of Aging.
View all literature mentionsMus musculus with name C3D2F1/J from IMSR.
View all literature mentionsMus musculus with name CByB6F1/J from IMSR.
View all literature mentionsMus musculus with name C3H/HeJ from IMSR.
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