Assessing Healthspan and Lifespan Measures in Aging Mice: Optimization of Testing Protocols, Replicability, and Rater Reliability
Stacey J. Sukoff Rizzo
Mouse Neurobehavioral Phenotyping Facility, Center for Biometric Analysis, The Jackson Laboratory, Bar Harbor, Maine
Corresponding author: [email protected]
Search for more papers by this authorLaura C. Anderson
Mouse Neurobehavioral Phenotyping Facility, Center for Biometric Analysis, The Jackson Laboratory, Bar Harbor, Maine
Search for more papers by this authorTorrian L. Green
Mouse Neurobehavioral Phenotyping Facility, Center for Biometric Analysis, The Jackson Laboratory, Bar Harbor, Maine
Search for more papers by this authorTracy McGarr
Mouse Neurobehavioral Phenotyping Facility, Center for Biometric Analysis, The Jackson Laboratory, Bar Harbor, Maine
Search for more papers by this authorGaylynn Wells
Mouse Neurobehavioral Phenotyping Facility, Center for Biometric Analysis, The Jackson Laboratory, Bar Harbor, Maine
Search for more papers by this authorShawn S. Winter
Mouse Neurobehavioral Phenotyping Facility, Center for Biometric Analysis, The Jackson Laboratory, Bar Harbor, Maine
Search for more papers by this authorStacey J. Sukoff Rizzo
Mouse Neurobehavioral Phenotyping Facility, Center for Biometric Analysis, The Jackson Laboratory, Bar Harbor, Maine
Corresponding author: [email protected]
Search for more papers by this authorLaura C. Anderson
Mouse Neurobehavioral Phenotyping Facility, Center for Biometric Analysis, The Jackson Laboratory, Bar Harbor, Maine
Search for more papers by this authorTorrian L. Green
Mouse Neurobehavioral Phenotyping Facility, Center for Biometric Analysis, The Jackson Laboratory, Bar Harbor, Maine
Search for more papers by this authorTracy McGarr
Mouse Neurobehavioral Phenotyping Facility, Center for Biometric Analysis, The Jackson Laboratory, Bar Harbor, Maine
Search for more papers by this authorGaylynn Wells
Mouse Neurobehavioral Phenotyping Facility, Center for Biometric Analysis, The Jackson Laboratory, Bar Harbor, Maine
Search for more papers by this authorShawn S. Winter
Mouse Neurobehavioral Phenotyping Facility, Center for Biometric Analysis, The Jackson Laboratory, Bar Harbor, Maine
Search for more papers by this authorAbstract
The relationship between chronological age (lifespan) and biological age (healthspan) varies amongst individuals. Understanding the normal trajectory and characteristic traits of aging mice throughout their lifespan is important for selecting the most reliable and reproducible measures to test hypotheses. The protocols herein describe assays used for aging studies at The Jackson Laboratory's Mouse Neurobehavioral Phenotyping Facility and include assessments of frailty, cognition, and sensory (hearing, vision, olfaction), motor, and fine motor function that can be used for assessing phenotypes in aged mice across their lifespan as well as provide guidance for setting up and validating these behavioral measures. Researchers aiming to study aging phenotypes require access to aged mice as a reference when initiating these types of studies in order to observe normal aging characteristics that cannot be observed in young adult mouse populations. © 2018 by John Wiley & Sons, Inc.
Literature Cited
- Bouet, V., Boulouard, M., Toutain, J., Divoux, D., Bernaudin, M., Schumann-Bard, P., & Freret, T. (2009). The adhesive removal test: A sensitive method to assess sensorimotor deficits in mice. Nature Protocols, 4(10), 1560–15644. doi: 10.1038/nprot.2009.125.
- Cheng, A., Morsch, M., Murata, Y., Ghazanfari, N., Reddel, S. W., & Phillips, W. D. (2013). Sequence of age-associated changes to the mouse neuromuscular junction and the protective effects of voluntary exercise. PLoS One, 8(7), e67970. doi: 10.1371/journal.pone.0067970.
- Clegg, A., & Young, J. (2011). The frailty syndrome. Clinical Medicine, 11(1), 72–75. doi: 10.7861/clinmedicine.11-1-72.
- Coyle, C. A., Strand, S. C., & Good, D. J. (2008). Reduced activity without hyperphagia contributes to obesity in Tubby mutant mice. Physiology & Behavior, 95(1–2), 168–175. doi: 10.1016/j.physbeh.2008.05.014.
- Crabbe, J. C., Wahlsten, D., & Dudek, B. C. (1999). Genetics of mouse behavior: Interactions with laboratory environment. Science, 284(5420), 1670–1672. doi: 10.1126/science.284.5420.1670.
- Dere, E., Kartteke, E., Huston, J., & De Souza Silva, M. (2006). The case for episodic memory in animals. Neuroscience & Biobehavioral Reviews, 30(8), 1206–1224. doi: 10.1016/j.neubiorev.2006.09.005.
- Doty, R. L. (2012). Olfaction in Parkinson's disease and related disorders. Neurobiology of Disease, 46(3), 527–552. doi: 10.1016/j.nbd.2011.10.026
- Eacott, M. J., & Easton, A. (2010). Episodic memory in animals: Remembering which occasion. Neuropsychologia, 48(8), 2273–2280. doi: 10.1016/j.neuropsychologia.2009.11.002.
- Eichenbaum, H., Sauvage, M., Fortin, N., Komorowski, R., & Lipton, P. (2012). Towards a functional organization of episodic memory in the medial temporal lobe. Neuroscience & Biobehavioral Reviews, 36(7), 1597–1608. doi: 10.1016/j.neubiorev.2011.07.006.
- Fahlström, A., Yu, Q., & Ulfhake, B. (2011). Behavioral changes in aging female C57BL/6 mice. Neurobiology of Aging, 32(10), 1868–1880. doi: 10.1016/j.neurobiolaging.2009.11.003.
- Fedarko, N. S. (2011). The biology of aging and frailty. Clinics in Geriatric Medicine, 27(1), 27–37. doi: 10.1016/j.cger.2010.08.006.
- Fleming, S. M., Ekhator, O. R., & Ghisays, V. (2013). Assessment of sensorimotor function in mouse models of Parkinson's disease. Journal of Visualized Experiments, 76, e50303. https://doi.org/10.3791/50303.
- Hughes, R. N. (2004). The value of spontaneous alternation behavior (SAB) as a test of retention in pharmacological investigations of memory. Neuroscience & Biobehavioral Reviews, 28(5), 497–505. doi:10.1016/j.neubiorev.2004.06.006.
- Kim, W. R., Lee, J. W., Sun, W., Lee, S., Choi, J., & Jung, M. W. (2015). Effect of dentate gyrus disruption on remembering what happened where. Frontiers in Behavioral Neuroscience, 9, 170. doi: 10.3389/fnbeh.2015.00170.
- Kohman, R. A., Rodriguez-Zas, S. L., Southey, B. R., Kelley, K. W., Dantzer, R., & Rhodes, J. S. (2011). Voluntary wheel running reverses age-induced changes in hippocampal gene expression. PLoS One, 6(8), e22654. doi: 10.1371/journal.pone.0022654.
- Kopp, C., Ressel, V., Wigger, E., & Tobler, I. (2006). Influence of estrus cycle and ageing on activity patterns in two inbred strains. Behavioural Brain Research, 167(1), 165–174. doi: 10.1016/j.bbr.2005.09.00.001.
- Lalonde, R. (2002). The neurobiological basis of spontaneous alternation. Neuroscience & Biobehavioral Reviews, 26(1), 91–104. doi: 10.1016/s0149-7634(01)00041-0.
- Lightfoot, J. T., Turner, M. J., Pomp, D., Kleeberger, S. R., & Leamy, L. J. (2008). Quantitative trait loci for physical activity traits in mice. Physiological Genomics, 32(3), 401–408. doi: 10.1152/physiolgenomics.00241.2007.
- Mandillo, S., Heise, I., Garbugino, L., Tocchini-Valentini, G. P., Giuliani, A., Wells, S., & Nolan, P. M. (2014). Early motor deficits in mouse disease models are reliably uncovered using an automated home-cage wheel-running system: A cross-laboratory validation. Disease Models & Mechanisms, 7(3), 397–407. doi: 10.1242/dmm.013946.
- McIlwain, K. L., Merriweather, M. Y., Yuva-Paylor, L. A., & Paylor, R. (2001). The use of behavioral test batteries: Effects of training history. Physiology & Behavior, 73(5), 705–717. doi: 10.1016/s0031-9384(01)00528-5.
- Mobley, A. S., Rodriguez-Gil, D. J., Imamura, F., & Greer, C. A. (2014). Aging in the olfactory system. Trends in Neuroscience, 37(2), 77–84. doi: 10.1016/j.tins.2013.11.004.
- Ouagazzal, A., Reiss, D., & Romand, R. (2006). Effects of age-related hearing loss on startle reflex and prepulse inhibition in mice on pure and mixed C57BL and 129 genetic background. Behavioural Brain Research, 172(2), 307–315. doi: 10.1016/j.bbr.2006.05.018.
- Parks, R. J., Fares, E., MacDonald, J. K., Ernst, M. C., Sinal, C. J., Rockwood, K., & Howlett, S. E. (2012). A procedure for creating a frailty index based on deficit accumulation in aging mice. The Journals of Gerontology: Series A, 67A(3), 217–227. doi: 10.1093/gerona/glr193.
- Paumier, K. L., Sukoff Rizzo, S. J., Berger, Z., Chen, Y., Gonzales, C., Kaftan, E., … Dunlop, J. (2013). Behavioral characterization of A53T mice reveals early and late stage deficits related to Parkinson's disease. PLoS One, 8(8), e70274. doi: 10.1371/journal.pone.0070274.
- Paylor, R., Spencer, C., Yuva-Paylor, L., & Piekedahl, S. (2006). The use of behavioral test batteries, II: Effect of test interval. Physiology & Behavior, 87(1), 95–102. doi: 10.1016/j.physbeh.2005.09.002.
- Pendergast, J. S., Branecky, K. L., Huang, R., Niswender, K. D., & Yamazaki, S. (2014). Wheel-running activity modulates circadian organization and the daily rhythm of eating behavior. Frontiers in Psychology, 5, 177. doi: 10.3389/fpsyg.2014.00177.
- Prusky, G. T., Alam, N. M., Beekman, S., & Douglas, R. M. (2004). Rapid quantification of adult and developing mouse spatial vision using a virtual optomotor system. Investigative Ophthalmology & Visual Science, 45(12), 4611. doi: 10.1167/iovs.04-0541.
- Rhodes, J. S. (2005). Neurobiology of mice selected for high voluntary wheel-running activity. Integrative and Comparative Biology, 45(3), 438–455. doi: 10.1093/icb/45.3.438.
- Rockwood, K., Fox, R. A., Stolee, P., Robertson, D., & Lynn, B. (1994). Frailty in elderly people: An evolving concept. Canadian Medical Association Journal, 150(4), 489–495.
- Rosenthal, N., & Brown, S. (2007). The mouse ascending: Perspectives for human-disease models. Nature Cell Biology, 9(9), 993–999. doi: 10.1038/ncb437.
- Sherwin, C. (1998). Voluntary wheel running: A review and novel interpretation. Animal Behaviour, 56(1), 11–27. doi: 10.1006/anbe.1998.0836.
- Shoji, H., Takao, K., Hattori, S., & Miyakawa, T. (2016). Age-related changes in behavior in C57BL/6J mice from young adulthood to middle age. Molecular Brain, 9(1), 11. doi: 10.1186/s13041-016-0191-9.
- Soffe, Z., Radley-Crabb, H. G., McMahon, C., Grounds, M. D., & Shavlakadze, T. (2016). Effects of loaded voluntary wheel exercise on performance and muscle hypertrophy in young and old male C57Bl/6J mice. Scandinavian Journal of Medicine & Science in Sports, 26(2), 172–188. doi: 10.1111/sms.12416.
- Sukoff Rizzo, S. J., & Silverman, J. L. (2016). Methodological considerations for optimizing and validating behavioral assays. Current Protocols in Mouse Biology, 6, 364–379. doi: 10.1002/cpmo.17.
- Voikar, V., Vasar, E., & Rauvala, H. (2004). Behavioral alterations induced by repeated testing in C57BL/6J and 129S2/Sv mice: Implications for phenotyping screens. Genes, Brain and Behavior, 3(1), 27–38. doi: 10.1046/j.1601-183X.2003.0044.x.
- Wahlsten, D., Metten, P., Phillips, T. J., Boehm, S. L., Burkhart-Kasch, S., Dorow, J., … Crabbe, J. C. (2003). Different data from different labs: Lessons from studies of gene-environment interaction. Journal of Neurobiology, 54(1), 283–311. doi: 10.1002/neu.10173.
- Whitehead, J. C., Hildebrand, B. A., Sun, M., Rockwood, M. R., Rose, R. A., Rockwood, K., & Howlett, S. E. (2014). A clinical frailty index in aging mice: Comparisons with frailty index data in humans. The Journals of Gerontology: Series A, 69(6), 621–632. doi: 10.1093/gerona/glt136.
- Xue, Q. L. (2011). The frailty syndrome: Definition and natural history. Clinics in Geriatric Medicine, 27(1), 1–15. doi: 10.1016/j.cger.2010.08.009.
- Zethof, T. J., Heyden, J. A., Tolboom, J. T., & Olivier, B. (1994). Stress-induced hyperthermia in mice: A methodological study. Physiology & Behavior, 55(1), 109–115. doi: 10.1016/0031-9384(94)90017-5.