Functional Aging in Male C57BL/6J Mice Across the Life-Span: A Systematic Behavioral Analysis of Motor, Emotional, and Memory Function to Define an Aging Phenotype

Bach, 1999, Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway., Proc. Natl. Acad. Sci. U. S. A., 96, 5280, 10.1371/10.1073/pnas.96.9.5280

Barnes, 1979, Memory deficits associated with senescence: a neuro physiological and behavioral study in the rat., J. Comp. Physiol. Psychol., 93, 74, 10.1037/h0077579

Bellantuono, 2020, A toolbox for the longitudinal assessment of healthspan in aging mice., Nat. Protoc., 15, 540, 10.1038/s41596-019-0256-1

Benice, 2006, Sex-differences in age-related cognitive decline in C57BL/6J mice associated with increased brain microtubule-associated protein 2 and synaptophysin immunoreactivity., Neuroscience, 137, 413, 10.1016/j.neuroscience.2005.08.029

Berthelot, 2019, An integrative modeling approach to the age-performance relationship in mammals at the cellular scale., Sci. Rep., 9, 10.1038/s41598-018-36707-3

Bishop, 2010, Neural mechanisms of ageing and cognitive decline., Nature, 464, 529, 10.1038/nature08983

Bohannon, 2011, Normal walking speed: a descriptive meta-analysis., Physiotherapy, 97, 182, 10.1016/j.physio.2010.12.004

Bohannon, 2006, Reference values for adult grip strength measured with a Jamar dynamometer: a descriptive meta-analysis., Physiotherapy, 92, 11, 10.1016/j.physio.2005.05.003

Börsch, 2021, Molecular and phenotypic analysis of rodent models reveals conserved and species-specific modulators of human sarcopenia., Commun. Biol., 4, 10.1038/s42003-021-01723-z

Borsini, 2002, Do animal models of anxiety predict anxiolytic-like effects of antidepressants?, Psychopharmacology (Berl.), 163, 121, 10.1007/s00213-002-1155-6

Broekkamp, 1986, Major tranquillizers can be distinguished from minor tranquillizers on the basis of effects on marble burying and swim-induced grooming in mice., Eur. J. Pharmacol., 126, 223, 10.1016/0014-2999(86)90051-8

Cès, 2018, Age-related vulnerability of pattern separation in C57BL/6J mice., Neurobiol. Aging, 62, 120, 10.1016/j.neurobiolaging.2017.10.013

Chia, 2005, The origins and uses of mouse outbred stocks., Nat. Genet., 37, 1181, 10.1038/ng1665

Clegg, 2013, Frailty in elderly people., Lancet, 381, 752, 10.1016/S0140-6736(12)62167-9

Coppola, 2014, Age-related spatial working memory deficits in homing pigeons (Columba livia)., Behav. Neurosci., 128, 666, 10.1037/bne0000013

Craig, 2015, The digital ageing atlas: integrating the diversity of age-related changes into a unified resource., Nucleic Acids Res., 43, D873, 10.1093/nar/gku843

Craik, 1996, The effects of divided attention on encoding and retrieval processes in human memory., J. Exp. Psychol. Gen., 125, 159, 10.1037/0096-3445.125.2.159

Craik, 2010, Effects of aging and divided attention on memory for items and their contexts., Psychol. Aging, 25, 968, 10.1037/a0020276

Craik, 1992, “Human memory,” in, The Handbook of Aging and Cognition, 51

Crane, 2017, Patterns of predator neophobia: a meta-analytic review., Proc. Biol. Sci., 284, 10.1098/rspb.2017.0583

Crawley, 2008, Behavioral phenotyping strategies for mutant mice., Neuron, 57, 809, 10.1016/j.neuron.2008.03.001

Creer, 2010, Running enhances spatial pattern separation in mice., Proc. Natl. Acad. Sci. U. S. A., 107, 2367, 10.1073/pnas.0911725107

da Costa, 2016, A synopsis on aging—theories, mechanisms and future prospects., Ageing Res. Rev., 29, 90, 10.1016/j.arr.2016.06.005

Davis, 1984, Protein synthesis and memory: a review., Psychol. Bull., 96, 518, 10.1037/0033-2909.96.3.518

De Beurs, 1999, Consequences of anxiety in older persons: its effect on disability, well-being and use of health services., Psychol. Med., 29, 583, 10.1017/s0033291799008351

de Magalhães, 2012, Genome-environment interactions that modulate aging: powerful targets for drug discovery., Pharmacol. Rev., 64, 88, 10.1124/pr.110.004499

Dean, 1981, Age-related differences in behavior across the life span of the C57BL/6J mouse., Exp. Aging Res., 7, 427, 10.1080/03610738108259823

Demetrius, 2006, Aging in mouse and human systems: a comparative study., Ann. N Y Acad. Sci., 1067, 66, 10.1196/annals.1354.010

Dong, 2016, Evidence for a limit to human lifespan., Nature, 538, 257, 10.1038/nature19793

Dutta, 2016, Men and mice: relating their ages., Life Sci., 152, 244, 10.1016/j.lfs.2015.10.025

Erdfelder, 1996, GPOWER: a general power analysis program., Behav. Res. Methods Instrum. Comput., 28, 1, 10.3758/bf03203630

Fanselow, 1990, Factors governing one-trial contextual conditioning., Anim. Learn. Behav., 18, 264, 10.3758/bf03205285

Faul, 2007, G∗Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences., Behav. Res. Methods, 39, 175, 10.3758/bf03193146

Flurkey, 2007, “Mouse models in aging research,” in, The Mouse in Biomedical Research (Second Edition), 637, 10.1016/b978-012369454-6/50074-1

Fried, 2001, Frailty in older adults: evidence for a phenotype., J. Gerontol. A Biol. Sci. Med. Sci., 56, M146, 10.1093/gerona/56.3.M146

Fryar, 2016, Anthropometric reference data for children and adults: United States, 2011-2014., Vital Health Stat., 3, 1

Gawel, 2019, Assessment of spatial learning and memory in the Barnes maze task in rodents-methodological consideration., Naunyn. Schmiedebergs Arch. Pharmacol., 392, 1, 10.1007/s00210-018-1589-y

Giezenaar, 2016, Ageing is associated with decreases in appetite and energy intake—a meta-analysis in healthy adults., Nutrients, 8, 10.3390/nu8010028

Goto, 2015, “The biological mechanisms of aging: a historical and critical overview,” in, Aging Mechanisms: Longevity, Metabolism, and Brain Aging, 3, 10.1007/978-4-431-55763-0_1

Graber, 2013, C57BL/6 neuromuscular healthspan scoring system., J. Gerontol. A Biol. Sci. Med. Sci., 68, 1326, 10.1093/gerona/glt032

Guillaume, 2011, Success and decline: top 10 tennis players follow a biphasic course., Med. Sci. Sports Exerc., 43, 2148, 10.1249/mss.0b013e31821eb533

Harburger, 2007, Age-dependent effects of environmental enrichment on spatial reference memory in male mice., Behav. Brain Res., 185, 43, 10.1016/j.bbr.2007.07.009

Hardt, 2013, Decay happens: the role of active forgetting in memory., Trends Cogn. Sci., 17, 111, 10.1016/j.tics.2013.01.001

Harrison, 2009, Endogenous anxiety and stress responses in water maze and Barnes maze spatial memory tasks., Behav. Brain Res., 198, 247, 10.1016/j.bbr.2008.10.015

Hoffman, 2016, A modified wire hanging apparatus for small animal muscle function testing., PLoS Curr., 8, 10.1371/currents.md.1e2bec4e78697b7b0ff80ea25a1d38be

Holmes, 2002, Behavioral profiles of inbred strains on novel olfactory, spatial and emotional tests for reference memory in mice., Genes Brain Behav., 1, 55, 10.1046/j.1601-1848.2001.00005.x

Hoyer, 2006, “Memory aging,” in, Handbook of the Psychology of Aging (Sixth Edition), 209

Irwin, 1968, Comprehensive observational assessment: Ia. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse., Psychopharmacologia, 13, 222, 10.1007/bf00401402

Jackson, 2021, Evidence for deficits in behavioural and physiological responses in aged mice relevant to the psychiatric symptom of apathy., Brain Neurosci. Adv., 5, 10.1177/23982128211015110

Jonasson, 2005, Meta-analysis of sex differences in rodent models of learning and memory: a review of behavioral and biological data., Neurosci. Biobehav. Rev., 28, 811, 10.1016/j.neubiorev.2004.10.006

Jones, 1968, The quantitative measurement of motor inco-ordination in naive mice using an accelerating rotarod., J. Pharm. Pharmacol., 20, 302, 10.1111/j.2042-7158.1968.tb09743.x

Kennard, 2011, Age sensitivity of behavioral tests and brain substrates of normal aging in mice., Front. Aging Neurosci., 3, 10.3389/fnagi.2011.00009

Kenyon, 2010, The genetics of ageing., Nature, 464, 504, 10.1038/nature08980

Kirkwood, 2005, Understanding the odd science of aging., Cell, 120, 437, 10.1016/j.cell.2005.01.027

Kojima, 2008, Inducible cAMP early repressor acts as a negative regulator for kindling epileptogenesis and long-term fear memory., J. Neurosci., 28, 6459, 10.1523/jneurosci.0412-08.2008

Kõks, 2016, Mouse models of ageing and their relevance to disease., Mech. Ageing Dev., 160, 41, 10.1016/j.mad.2016.10.001

Kuhla, 2013, Lifelong caloric restriction increases working memory in mice., PLoS One, 8, 10.1371/journal.pone.0068778

Kuro-o, 1997, Mutation of the mouse klotho gene leads to a syndrome resembling ageing., Nature, 390, 45, 10.1038/36285

Lione, 1999, Selective discrimination learning impairments in mice expressing the human Huntington’s disease mutation., J. Neurosci., 19, 10428, 10.1523/jneurosci.19-23-10428.1999

López-Otín, 2013, The hallmarks of aging., Cell, 153, 1194, 10.1016/j.cell.2013.05.039

Ma, 2018, Caloric restriction can improve learning and memory in C57/BL mice probably via regulation of the AMPK signaling pathway., Exp. Gerontol., 102, 28, 10.1016/j.exger.2017.11.013

Maei, 2009, What is the most sensitive measure of water maze probe test performance?, Front. Integr. Neurosci., 3, 10.3389/neuro.07.004.2009

Magnusson, 2003, Age-related deficits in mice performing working memory tasks in a water maze., Behav. Neurosci., 117, 485, 10.1037/0735-7044.117.3.485

Matsuda, 2015, Sex differences in fear extinction and involvements of extracellular signal-regulated kinase (ERK)., Neurobiol. Learn. Mem., 123, 117, 10.1016/j.nlm.2015.05.009

McDowd, 1988, Effects of aging and task difficulty on divided attention performance., J. Exp. Psychol. Hum. Percept. Perform., 14, 267, 10.1037/0096-1523.14.2.267

Miller, 2000, Principles of animal use for gerontological research., J. Gerontol. A Biol. Sci. Med. Sci., 55, B117, 10.1093/gerona/55.3.B117

Mitchell, 2015, Animal models of aging research: implications for human aging and age-related diseases., Annu. Rev. Anim. Biosci., 3, 283, 10.1146/annurev-animal-022114-110829

Monastero, 2009, A systematic review of neuropsychiatric symptoms in mild cognitive impairment., J. Alzheimers Dis., 18, 11, 10.3233/jad-2009-1120

Morris, 1982, Place navigation impaired in rats with hippocampal lesions., Nature, 297, 681, 10.1038/297681a0

Morris, 1981, Spatial localization does not require the presence of local cues., Learn. Motiv., 12, 239, 10.1016/0023-9690(81)90020-5

Nasreddine, 2005, The montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment., J. Am. Geriatr. Soc., 53, 695, 10.1111/j.1532-5415.2005.53221.x

Njung’e, 1991, Evaluation of marble-burying behavior as a model of anxiety., Pharmacol. Biochem. Behav., 38, 63, 10.1016/0091-3057(91)90590-x

Nolte, 2019, Anxiety and task performance changes in an aging mouse model., Biochem. Biophys. Res. Commun., 514, 246, 10.1016/j.bbrc.2019.04.049

Nyberg, 2012, Memory aging and brain maintenance., Trends Cogn. Sci., 16, 292, 10.1016/j.tics.2012.04.005

Oellrich, 2016, Reporting phenotypes in mouse models when considering body size as a potential confounder., J. Biomed. Semantics, 7, 10.1186/s13326-016-0050-8

Orme, 1986, Factorial and discriminant validity of the center for epidemiological studies depression (CES-D) scale., J. Clin. Psychol., 42, 28, 10.1002/1097-4679(198601)42:1<28::aid-jclp2270420104>3.0.co;2-t

Pellow, 1985, Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat., J. Neurosci. Methods, 14, 149, 10.1016/0165-0270(85)90031-7

Phillips, 1992, Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning., Behav. Neurosci., 106, 274, 10.1037/0735-7044.106.2.274

Porsolt, 1977, Depression: a new animal model sensitive to antidepressant treatments., Nature, 266, 730, 10.1038/266730a0

Prince, 2015, World Alzheimer Report 2015—The Global Impact of Dementia. An Analysis of Prevalence, Incidence, Cost &amp; Trends.

Rando, 2021, Asynchronous, contagious and digital aging., Nat. Aging, 1, 29, 10.1038/s43587-020-00015-1

Rantanen, 1999, Midlife hand grip strength as a predictor of old age disability., JAMA, 281, 558, 10.1001/jama.281.6.558

Rapp, 1997, Impaired spatial information processing in aged monkeys with preserved recognition memory., Neuroreport, 8, 1923, 10.1097/00001756-199705260-00026

Remes, 2016, A systematic review of reviews on the prevalence of anxiety disorders in adult populations., Brain Behav., 6, 10.1002/brb3.497

Richardson, 2011, Anxiety and its correlates among older adults accessing aging services., Int. J. Geriatr. Psychiatry, 26, 31, 10.1002/gps.2474

Rosenzweig, 2003, Impact of aging on hippocampal function: plasticity, network dynamics, and cognition., Prog. Neurobiol., 69, 143, 10.1016/s0301-0082(02)00126-0

Rossetti, 2011, Normative data for the Montreal Cognitive Assessment (MoCA) in a population-based sample., Neurology, 77, 1272, 10.1212/wnl.0b013e318230208a

Rowe, 1987, Human aging: usual and successful., Science, 237, 143, 10.1126/science.3299702

Russell, 1959, The Principles of Human Experimental Technique.

Sadeh, 2014, How we forget may depend on how we remember., Trends Cogn. Sci., 18, 26, 10.1016/j.tics.2013.10.008

Serradj, 2007, Age-related changes in the motricity of the inbred mice strains 129/sv and C57BL/6j., Behav. Brain Res., 177, 80, 10.1016/j.bbr.2006.11.001

Shansky, 2019, Animal studies in both sexes., Science, 364, 825, 10.1126/science.aaw7570

Sharkey, 1987, Functional vs chronololgical age., Med. Sci. Sports Exerc., 19, 174, 10.1249/00005768-198704000-00018

Shepherd, 1994, Behavioural and pharmacological characterisation of the elevated “zero-maze” as an animal model of anxiety., Psychopharmacology (Berl.), 116, 56, 10.1007/bf02244871

Shoji, 2016, Age-related changes in behavior in C57BL/6J mice from young adulthood to middle age., Mol. Brain, 9, 10.1186/s13041-016-0191-9

Sohal, 2014, Caloric restriction and the aging process: a critique., Free Radic. Biol. Med., 73, 366, 10.1016/j.freeradbiomed.2014.05.015

Speakman, 2010, Associations between energy demands, physical activity, and body composition in adult humans between 18 and 96 y of age., Am. J. Clin. Nutr., 92, 826, 10.3945/ajcn.2009.28540

Spröwitz, 2013, Sex-specific positive and negative consequences of avoidance training during childhood on adult active avoidance learning in mice., Front. Behav. Neurosci., 7, 10.3389/fnbeh.2013.00143

Stark, 2013, A task to assess behavioral pattern separation (BPS) in humans: data from healthy aging and mild cognitive impairment., Neuropsychologia, 51, 2442, 10.1016/j.neuropsychologia.2012.12.014

Stewart, 2011, Which memory task for my mouse? A systematic review of spatial memory performance in the Tg2576 Alzheimer’s mouse model., J. Alzheimers Dis., 26, 105, 10.3233/jad-2011-101827

Sumien, 2006, Profiling psychomotor and cognitive aging in four-way cross mice., Age (Dordr.), 28, 265, 10.1007/s11357-006-9015-7

Sundberg, 2011, The mouse as a model for understanding chronic diseases of aging: the histopathologic basis of aging in inbred mice., Pathobiol. Aging Age Relat. Dis., 1, 10.3402/pba.v1i0.7179

Takahashi, 2019, Vitamin C and vitamin E double-deficiency increased neuroinflammation and impaired conditioned fear memory., Arch. Biochem. Biophys., 663, 120, 10.1016/j.abb.2019.01.003

Takeda, 1981, A new murine model of accelerated senescence., Mech. Ageing Dev., 17, 183, 10.1016/0047-6374(81)90084-1

Takeshita, 2017, Modified forelimb grip strength test detects aging-associated physiological decline in skeletal muscle function in male mice., Sci. Rep., 7, 10.1038/srep42323

Tarantini, 2019, Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice., Redox Biol., 24, 10.1016/j.redox.2019.101192

Taylor, 2017, Marble burying as compulsive behaviors in male and female mice., Acta Neurobiol. Exp. (Wars.), 77, 254, 10.21307/ane-2017-059

Thomas, 2009, Marble burying reflects a repetitive and perseverative behavior more than novelty-induced anxiety., Psychopharmacology (Berl.), 204, 361, 10.1007/s00213-009-1466-y

Tomitaka, 2015, Right tail of the distribution of depressive symptoms is stable and follows an exponential curve during middle adulthood., PLoS One, 10, 10.1089/neu.2015.3977

Tucker, 2016, Performance of male and female C57BL/6J mice on motor and cognitive tasks commonly used in pre-clinical traumatic brain injury research., J. Neurotrauma, 33, 880, 10.1089/neu.2015.377

Tveter, 2014, Health-related physical fitness measures: reference values and reference equations for use in clinical practice., Arch. Phys. Med. Rehabil., 95, 1366, 10.1016/j.apmr.2014.02.016

Vellas, 2016, White Book on Frailty.

Wald, 2010, Of mice and women: the bias in animal models., Science, 327, 1571, 10.1126/science.327.5973.1571

Walsh, 1976, The open-field test: a critical review., Psychol. Bull., 83, 482, 10.1037/0033-2909.83.3.482

Ware, 2003, Utility of a C57BL/6 ES line versus 129 ES lines for targeted mutations in mice., Transgenic Res., 12, 743, 10.1023/b:trag.0000005246.35812.c8

Weber, 2015, Cognitive deficits, changes in synaptic function, and brain pathology in a mouse model of normal aging., eNeuro, 2, e47, 10.1523/ENEURO.0047-15.2015

2015, World Report on Ageing and Health.

Wolmarans, 2016, Of mice and marbles: novel perspectives on burying behavior as a screening test for psychiatric illness., Cogn. Affect. Behav. Neurosci., 16, 551, 10.3758/s13415-016-0413-8

Yanai, 2016, Early onset of behavioral alterations in senescence-accelerated mouse prone 8 (SAMP8)., Behav. Brain Res., 308, 187, 10.1016/j.bbr.2016.04.026

Yanai, 2018, Long-term cilostazol administration prevents age-related decline of hippocampus-dependent memory in mice., Neuropharmacology, 129, 57, 10.1016/j.neuropharm.2017.11.008

Yanai, 2012, Remarkable changes in behavior and physiology of laboratory mice after the massive 2011 Tohoku earthquake in Japan., PLoS One, 7, 10.1371/journal.pone.0044475

Yanai, 2014, Cilostazol improves hippocampus-dependent long-term memory in mice., Psychopharmacology (Berl.), 231, 2681, 10.1007/s00213-014-3442-4

Yassa, 2011, Pattern separation deficits associated with increased hippocampal CA3 and dentate gyrus activity in nondemented older adults., Hippocampus, 21, 968, 10.1002/hipo.20808

Yates, 2013, Mild cognitive impairment and mood: a systematic review., Rev. Clin. Gerontol., 23, 317, 10.1017/s0959259813000129

Yuan, 2009, Aging in inbred strains of mice: study design and interim report on median lifespans and circulating IGF1 levels., Aging Cell, 8, 277, 10.1111/j.1474-9726.2009.00478.x

Zeidner, 2014, “Anxiety in education,” in, International Handbook of Emotions in Education, 265

Zhu, 2010, Adequacy and change in nutrient and food intakes with aging in a seven-year cohort study in elderly women., J. Nutr. Health Aging, 14, 723, 10.1007/s12603-010-0324-2