Research Paper Volume 11, Issue 17 pp 7150—7168

Conclusions from a behavioral aging study on male and female F2 hybrid mice on age-related behavior, buoyancy in water-based tests, and an ethical method to assess lifespan

Julia Adelöf1,2, , Jaime M. Ross3,4, , Stanley E. Lazic5,6, , Madeleine Zetterberg1, , John Wiseman2, , Malin Hernebring1,2, ,

  • 1 Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg 41390, Sweden
  • 2 Discovery Biology, Discovery Sciences, R&D AstraZeneca, Gothenburg, Mölndal 43153, Sweden
  • 3 Department of Genetics, Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA 02215, USA
  • 4 Department of Neuroscience, Biomedicum, Karolinska Institutet, Stockholm 17165, Sweden
  • 5 Quantitative Biology, Discovery Sciences, R&D AstraZeneca, Cambridge CB4 0WG, UK
  • 6 Current address: Inc., Ottawa K2P 2N2, Canada

Received: May 23, 2019       Accepted: August 22, 2019       Published: September 11, 2019
How to Cite

Copyright © 2019 Adelöf et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Due to strain-specific behavioral idiosyncrasies, inbred mouse strains are suboptimal research models for behavioral aging studies. The aim of this study is to determine age-related behavioral changes of F2 hybrid C57BL/6NxBALB/c male and female mice. Lifespan was followed (nmales=48, nfemales=51) and cohorts of mature adult (7 months), middle-aged (15 months), and old mice (22 months of age; n=7-12 per group) were assessed regarding open-field activity, exploration, passive avoidance learning/memory, and depressive-like behavior. We found that both males and females demonstrated decreased exploratory behavior with age, while memory and depressive-like behavior were maintained. Females exhibited enhanced depressive-like behavior compared to males; however, a correlation between fat mass and swimming activity in the test directly accounted for 30-46% of this behavioral sex difference. In addition, we suggest a method to qualitatively estimate natural lifespan from survival analyses in which animals with signs of pain or severe disease are euthanized. This is, to our knowledge, the first behavioral study to consider both sex and aging in hybrid mice. We here define decreased exploratory behavior as a conserved hallmark of aging independent of sex, highlight the effect of buoyancy in water tests, and provide a method to assay lifespan with reduced animal suffering.


DEXA: dual energy X-ray absorptiometry; BMC: bone mineral content; BMD: bone mineral density; PAT: passive avoidance test.