Cited by 369Animal testing and alternativesGenetics, Aging, and Longevity in Model OrganismsVeterinary Pharmacology and Anesthesia

Does age matter? The impact of rodent age on study outcomes

Open access
Jackson, Samuel J, Andrews, Nick, Ball, Doug, Bellantuono, Ilaria, Gray, James, Hachoumi, Lamia, Holmes, Alan, Latcham, Judy +8 more·2017·Laboratory Animals

Abstract

Rodent models produce data which underpin biomedical research and non-clinical drug trials, but translation from rodents into successful clinical outcomes is often lacking. There is a growing body of evidence showing that improving experimental design is key to improving the predictive nature of rodent studies and reducing the number of animals used in research. Age, one important factor in experimental design, is often poorly reported and can be overlooked. The authors conducted a survey to assess the age used for a range of models, and the reasoning for age choice. From 297 respondents providing 611 responses, researchers reported using rodents most often in the 6–20 week age range regardless of the biology being studied. The age referred to as ‘adult’ by respondents varied between six and 20 weeks. Practical reasons for the choice of rodent age were frequently given, with increased cost associated with using older animals and maintenance of historical data comparability being two important limiting factors. These results highlight that choice of age is inconsistent across the research community and often not based on the development or cellular ageing of the system being studied. This could potentially result in decreased scientific validity and increased experimental variability. In some cases the use of older animals may be beneficial. Increased scientific rigour in the choice of the age of rodent may increase the translation of rodent models to humans.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1177/0023677216653984

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • For most species, precise reporting of age is more informative than a description of the developmental status.

    “For most species, precise reporting of age is more informative than a description of the developmental status (e.g., a mouse referred to as an adult can vary in age from 6 to 20 weeks [108]).”

    From Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0 (2020) · cites this paper as [108]

    The Discussion (‘Age considered “adult”’) recommends reporting actual age instead of a life-stage term, and the Results show that ‘adult’ covered 6–20 weeks for mice. The paper examines rodents, however, so it does not establish the claim for ‘most species.’ (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 50 · Cited by 369

Research works printed but not linked: 45

  1. [1]Festing MF Altman DG Guidelines for the design and statistical analysis of experiments using laboratory animals. ILAR J 2002; 43: 244– 258. 12391400
  2. [2]Kilkenny C Browne WJ Cuthill IC Emerson M Altman DG Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol 2010; 8: e1000412– e1000412. 20613859 PMC2893951
  3. [4]Adams DJ The Valley of Death in anticancer drug development: a reassessment. Trends Pharmacol Sci 2012; 33: 173– 180. 22410081 PMC3324971
  4. [5]Talevi A Bellera CL Di Ianni M Gantner M Bruno-Blanch LE Castro EA CNS drug development – lost in translation? Mini Rev Med Chem 2012; 12: 959– 970. 22420574
  5. [6]Bandeira F Lent R Herculano-Houzel S Changing numbers of neuronal and non-neuronal cells underlie postnatal brain growth in the rat. Proc Natl Acad Sci USA 2009; 106: 14108– 14113. 19666520 PMC2729028
  6. [7]Somerville JM Aspden RM Armour KE Armour KJ Reid DM Growth of C57BL/6 mice and the material and mechanical properties of cortical bone from the tibia. Calcif Tissue Int 2004; 74: 469– 475. 14961209
  7. [8]Carnieli DS Yoshioka E Silva LF Inflammation and remodeling in infantile, juvenile, and adult allergic sensitized mice. Pediatr Pulmonol 2011; 46: 650– 665. 21360835
  8. [9]Astori M Finke D Karapetian O Acha-Orbea H Development of T–B cell collaboration in neonatal mice. Int Immunol 1999; 11: 445– 451. 10221656
  9. [10]Downes N Mullins P The development of myelin in the brain of the juvenile rat. Toxicol Pathol 2013; 42: 913– 922. 24129760
  10. [11]Fu Y Rusznak Z Herculano-Houzel S Watson C Paxinos G Cellular composition characterizing postnatal development and maturation of the mouse brain and spinal cord. Brain Struct Funct 2013; 218: 1337– 1354. 23052551
  11. [12]Brodt MD Ellis CB Silva MJ Growing C57BL/6 mice increase whole bone mechanical properties by increasing geometric and material properties. J Bone Miner Res 1999; 14: 2159– 2166. 10620076
  12. [13]Halloran BP Ferguson VL Simske SJ Burghardt A Venton LL Majumdar S Changes in bone structure and mass with advancing age in the male C57BL/6J mouse. J Bone Miner Res 2002; 17: 1044– 1050. 12054159
  13. [14]Holsapple MP West LJ Landreth KS Species comparison of anatomical and functional immune system development. Birth Defects Res B Dev Reprod Toxicol 2003; 68: 321– 334. 14666995
  14. [15]Kay MM Mendoza J Diven J Denton T Union N Lajiness M Age-related changes in the immune system of mice of eight medium and long-lived strains and hybrids. I. Organ, cellular, and activity changes. Mech Ageing Dev 1979; 11: 295– 346. 316845
  15. [16]Velardi A Cooper MD An immunofluorescence analysis of the ontogeny of myeloid, T, and B lineage cells in mouse hemopoietic tissues. J Immunol 1984; 133: 672– 677. 6429241
  16. [17]Ghia P ten Boekel E Rolink AG Melchers F B-cell development: a comparison between mouse and man. Immunol Today 1998; 19: 480– 485. 9785673
  17. [18]Holladay SD Smialowicz RJ Development of the murine and human immune system: differential effects of immunotoxicants depend on time of exposure. Environ Health Perspect 2000; 108(Suppl 3): 463– 473. PMC1637831 10852846
  18. [19]Kincade PW Formation of B lymphocytes in fetal and adult life. Adv Immunol 1981; 31: 177– 245. 7032254
  19. [20]Wauthier V Verbeeck RK Calderon PB The effect of ageing on cytochrome p450 enzymes: consequences for drug biotransformation in the elderly. Curr Med Chem 2007; 14: 745– 757. 17346160
  20. [21]Palasz A Wiaderkiewicz A Wiaderkiewicz R Age-related changes in the mRNA levels of CYP1A1, CYP2B1/2 and CYP3A1 isoforms in rat small intestine. Genes Nutr 2012; 7: 197– 207. 21769602 PMC3316744
  21. [22]Greaves LC Barron MJ Campbell-Shiel G Kirkwood TB Turnbull DM Differences in the accumulation of mitochondrial defects with age in mice and humans. Mech Ageing Dev 2011; 132: 588– 591. 22015485
  22. [23]Nelson JF Felicio LS Osterburg HH Finch CE Differential contributions of ovarian and extraovarian factors to age-related reductions in plasma estradiol and progesterone during the estrous cycle of C57BL/6J mice. Endocrinology 1992; 130: 805– 810. 1733727
  23. [24]Mobbs CV Cheyney D Sinha YN Finch CE Age-correlated and ovary-dependent changes in relationships between plasma estradiol and luteinizing hormone, prolactin, and growth hormone in female C57BL/6J mice. Endocrinology 1985; 116: 813– 820. 3967630
  24. [25]Bouxsein ML Myers KS Shultz KL Donahue LR Rosen CJ Beamer WG Ovariectomy-induced bone loss varies among inbred strains of mice. J Bone Miner Res 2005; 20: 1085– 1092. 15940361
  25. [26]Ankolekar S Rewell S Howells DW Bath PM The influence of stroke risk factors and comorbidities on assessment of stroke therapies in humans and animals. Int J Stroke 2012; 7: 386– 397. 22712740
  26. [27]Shapira S Sapir M Wengier A Grauer E Kadar T Aging has a complex effect on a rat model of ischemic stroke. Brain Res 2002; 925: 148– 158. 11792363
  27. [28]Yager JY Thornhill JA The effect of age on susceptibility to hypoxic–ischemic brain damage. Neurosci Biobehav Rev 1997; 21: 167– 174. 9062939
  28. [29]Brown AW Marlowe KJ Bjelke B Age effect on motor recovery in a post-acute animal stroke model. Neurobiol Aging 2003; 24: 607– 614. 12714118
  29. [30]Toye AA Lippiat JD Proks P A genetic and physiological study of impaired glucose homeostasis control in C57BL/6J mice. Diabetologia 2005; 48: 675– 686. 15729571
  30. [32]Ghosh D Levault KR Brewer GJ Relative importance of redox buffers GSH and NAD(P)H in age-related neurodegeneration and Alzheimer disease-like mouse neurons. Aging Cell 2014; 13: 631– 640. 24655393 PMC4116450
  31. [33]Johnson KR Zheng QY Noben-Trauth K Strain background effects and genetic modifiers of hearing in mice. Brain Res 2006; 1091: 79– 88. 16579977 PMC2858224
  32. [34]Langille MG Meehan CJ Koenig JE Microbial shifts in the aging mouse gut. Microbiome 2014; 2: 50– 50. 25520805 PMC4269096
  33. [35]Vital M Harkema JR Rizzo M Tiedje J Brandenberger C Alterations of the murine gut microbiome with age and allergic airway disease. J Immunol Res 2015; 2015: 892568– 892568. 26090504 PMC4451525
  34. [36]Mori K Blackshear PE Lobenhofer EK Hepatic transcript levels for genes coding for enzymes associated with xenobiotic metabolism are altered with age. Toxicol Pathol 2007; 35: 242– 251. 17366318
  35. [37]Pibiri M Sulas P Leoni VP Global gene expression profile of normal and regenerating liver in young and old mice. Age (Dordr) 2015; 37: 9796– 9796. 26036689 PMC4451458
  36. [40]Quinn R Comparing rat’s to human’s age: how old is my rat in people years? Nutrition 2005; 21: 775– 777. 15925305
  37. [41]Flurkey K Currer JM Harrison DE Mouse models in aging research. In: Fox JG Davisson MT Quimby FW Barthold SW Newcomer CE Smith AL (eds). The mouse in biomedical research, 2nd ed. Burlington: Academic Press, 2007, pp. 637– 672.
  38. [42]Sengupta P The laboratory rat: relating its age with humans. Int J Prev Med 2013; 4: 624– 630. 23930179 PMC3733029
  39. [43]Mulvey L Sinclair A Selman C Lifespan modulation in mice and the confounding effects of genetic background. J Genet Genomics (Yi chuan xue bao) 2014; 41: 497– 503. 25269675 PMC4257991
  40. [44]Banks G Heise I Starbuck B Genetic background influences age-related decline in visual and nonvisual retinal responses, circadian rhythms, and sleep. Neurobiol Aging 2015; 36: 380– 393. 25179226 PMC4270439
  41. [46]Clancy B Kersh B Hyde J Darlington RB Anand KJ Finlay BL Web-based method for translating neurodevelopment from laboratory species to humans. Neuroinformatics 2007; 5: 79– 94. 17426354
  42. [47]Maddatu TP Grubb SC Bult CJ Bogue MA Mouse Phenome Database (MPD). Nucleic Acids Res 2012; 40: D887– D894. 22102583 PMC3245053
  43. [49]Geifman N Rubin E The mouse age phenome knowledgebase and disease-specific inter-species age mapping. PLoS One 2013; 8: e81114– e81114. 24312529 PMC3849212
  44. [50]de la Cruz N Bromberg S Pasko D The Rat Genome Database (RGD): developments towards a phenome database. Nucleic Acids Res 2005; 33: D485– D491. 15608243 PMC540004
  45. [51]Duran AL Potter P Wells S Shared Ageing Research Models (ShARM): a new facility to support ageing research. Biogerontology 2013; 14: 789– 794. 24085518 PMC3847282

Authors
Jackson, S. J., Andrews, N., Ball, D., Bellantuono, I., Gray, J., Hachoumi, L., Holmes, A., Latcham, J., Petrie, A., Potter, P., Rice, A., Ritchie, A., Stewart, M., Strepka, C., Yeoman, M., & Chapman, K.
Affiliations
  • National Centre for the Replacement Refinement and Reduction of Animals in Research (GB)
  • Boston Children's Hospital (US)
  • GlaxoSmithKline (United Kingdom) (GB)
  • University of Sheffield (GB)
  • University of Brighton (GB)
  • The Royal Free Hospital (GB)
  • University of Aberdeen (GB)
  • Mary Lyon Centre at MRC Harwell (GB)
  • Imperial College London (GB)
  • University of Nottingham (GB)
  • Preclinical Services, Charles River, Edinburgh, UK
Corresponding author
Jackson, Samuel J
Venue
Laboratory Animals
Published
2016-07-10
Volume
51
Issue
2
Pages
160-169
ISSN
  • 0023-6772 (ISSN-L)
  • 1758-1117
OpenAlex
W2430937405
Cited by
369
References
50
Citations by year
2026: 43 · 2025: 64 · 2024: 56 · 2023: 43 · 2022: 52 · 2021: 35 · 2020: 29 · 2019: 23 · 2018: 16 · 2017: 7
FWCI
23.58
Type
journal article
Language
en
Open access
Locations
  • Laboratory Animals (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
  • University of Brighton Repository (University of Brighton) (acceptedVersion, cc-by)
  • UCL Discovery (University College London) (submittedVersion)
  • St Andrews Research Repository (St Andrews Research Repository) (submittedVersion, cc-by)
  • Spiral (Imperial College London) (submittedVersion, other-oa)
Funders
  • GlaxoSmithKline
  • University of Brighton
  • Medical Research Council (MR/K006312/1)
Topics
  • Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Veterinary › Small Animals › Veterinary Pharmacology and Anesthesia
Keywords
animal models, experimental design, translational research, research reporting practices, animal use reduction, scientific validity, experimental variability
MeSH terms
Age Factors, Aging, Animals, Terminology as Topic, Biomedical Research, Mice, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review