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Behavioral battery in mice to model age-associated changes in human motor function

Behavioral battery in mice to model age-associated changes in human motor function . Jamie N. Justice, Ph.D. Department of Integrative Physiology, University of Colorado Boulder. Assessing physical function across species: Mice, monkeys and man Gerontological Society of America, Nov 2013.

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Behavioral battery in mice to model age-associated changes in human motor function

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  1. Behavioral battery in mice to model age-associated changes in human motor function • Jamie N. Justice, Ph.D. Department of Integrative Physiology, University of Colorado Boulder Assessing physical function across species: Mice, monkeys and man Gerontological Society of America, Nov 2013

  2. Standardized batteries of physical function tests have long been in use in clinical practice & aging research in humans Improve quality of clinical aging research Provide “common currency”

  3. Though rodent behavior has long been used in aging research... Analogous batteries in mice? Validate against human declines?

  4. Mouse models in aging research: Mechanisms -access to tissue -signaling pathways -genetic knock outs -disease models Screen interventions -prevention -treatment -safety -efficacy Longitudinal Research -survival studies -optimal intervention time Translation

  5. Physical Function Mouse Model Aim: To develop and assess the validity of a battery of tests to characterize motor function in mice Strength Endurance Locomotion Balance face validity wide spread use in behavioral testing established use in aging research economy of time and effort Justice JN, Carter CS, Beck HJ, Gioscia-Ryan RA, McQueen M, Enoka RM, Seals DR. AGE, 2013.

  6. Mouse Model of Physical Function the ability to generate a maximal force against physical objects - NIH Toolbox Strength Endurance Locomotion Balance Grip Strength: average force at forepaw release

  7. Mouse Model of Physical Function the ability to move from place to place -NIH Toolbox Strength Endurance Locomotion Balance Open Field Distance: Distance traveled over 5 min “Scurry” Speed: average speed to cover straight walking track Rearing Counts: Number of rears over 3 min

  8. Mouse Model of Physical Function the ability to orient the body in space, maintain an upright posture under both static and dynamic conditions, and move and walk without falling -NIH Toolbox Strength Endurance Locomotion Balance Accelerating Rota-Rod: average latency to fall from accelerating rotating rod Hindlimb Grasp: latency to grasp tightrope with hind limbs once suspended by forepaws

  9. Mouse Model of Physical Function how long a person (animal) can perform an activity at a particular intensity -NIH Toolbox Strength Endurance Locomotion Balance Tightrope: maximum time suspended from tightrope Rota-Rod Run: maximum time and distance run until falling off the rota-rod

  10. 20 month 3 month 26 month n = 87 n = 48 n = 42 10

  11. 20 month 3 month 26 month Normalized Scores (0-1 scale): 1 - (worst / current) Average Average Average Average

  12. * * * * * * * * * Physical function declines with age in mice

  13. Physical function declines with age How do these subdomains relate to declines seen in humans? Systematic Review 21 articles included with normative data from young and old humans Percent declines from young were calculated for humans and mice Determine relative lifespan points for mice and humans

  14. 12 42.5 30 69 81 94 56 Human age equivalents (years) Relative lifespans for mice and humans 100 75 Percentage of survivors 50% survivorship 50 25 0 1 6 12 18 24 30 36 Mouse age (months) 1 1 Adapted from “The Mouse in Biomedical Research: Normative Biology, Husbandry, and Models” 14

  15. Human Mice Locomotion Endurance Balance Strength Physical function declines with age

  16. Physical Function Strength Endurance Locomotion Balance

  17. Acknowledgements Christy Carter, Ph.D. Roger M. Enoka, Ph.D. Douglas R. Seals, Ph.D. Rachel Gioscia-Ryan, M.S. Hannah J. Beck Matthew McQueen, Ph.D.

  18. Which tests are most reflective of Summary Score?

  19. Which subdomains are most reflective of Summary Score?

  20. Order of test presentation

  21. Thank you “Put a bird on it” Jamie Justice, IPHY Colloquium Presentation, 2013

  22. Best Worst Worst Best Performance at Midlife Physical function at midlife is predictive of lifespan in rats Swim Speed & Incline Plane Task Dependency? Normalized Scores (0-1 scale): 1 - (worst / current) Best Carter CS, Sonntag WE, Onder G, Pahor M. J Gerontol A Biol Sci Med Sci, 2002

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