Blog Post November 13, 2017

Five must-reads if you study aging in mice

Aging studies present unique considerations due to their long duration and the significant amount of resources they require. JAX provides study-ready C57BL/6J males and females that are between 25-78 weeks of age. These mice are managed by JAX’s Genetic Stability Program and husbandry experts to minimize genetic drift. Visit the Aged C57BL/6J mouse page to learn more.

The following five references make recommendations that can improve their translational relevance, accuracy, and reproducibility.

Better Planning

Aging studies with mice should include all relevant stakeholders in planning and conducting the work:

An effective aging research program includes the collaboration and education of the research, husbandry, and veterinary staff, and of the members of the institution’s animal care and use committee. This collaborative effort is critical to humanely maintaining older mice and preventing excessive censorship due to non-lethal diseases. Part of the educational process is becoming familiar with how old mice appear clinically, at necropsy and histopathologically. This baseline knowledge is important in making the determination of humane end points, defining health span, contributing causes of death and effects of interventions.

Pettan-Brewer and Treuting, 2011

 The approach and details will vary with the aims of different studies; however, these three references will help improve design, implementation, and analysis for aging studies involving mice:

  1. Pettan-Brewer, C., and P. M. Treuting. 2011. “Practical pathology of aging mice,” Pathobiol Aging Age Relat Dis, 1. PMID: 22953032 
  2. Brayton, C. F., P. M. Treuting, and J. M. Ward. 2012. “Pathobiology of aging mice and GEM: background strains and experimental design,” Vet Pathol, 49: 85-105. PMID: 22215684 
  3. Treuting, P. M., J. M. Snyder, Y. Ikeno, P. N. Schofield, J. M. Ward, and J. P. Sundberg. 2016. “The Vital Role of Pathology in Improving Reproducibility and Translational Relevance of Aging Studies in Rodents,” Vet Pathol, 53: 244-9. PMID: 26792843

Better Reporting

Reproducibility has emerged as a significant concern, particularly for investigations using animal models. A failure to address the issue has the potential to erode public trust in science, waste valuable research resources, and further delay discoveries that could improve human health. Environmental factors such as diet, housing, and health status represent a highly significant potential source of phenotypic variation, especially for long term studies:

There needs to be increased awareness of these factors within the community but, as importantly, these parameters need to be captured and shared with publications. The ARRIVE guidelines cover all of the parameters identified here in detail and yet there is still a problem in persuading authors to provide this information and for journals to enforce their own policies. …

The bottom line, however, is that it is only with a firm commitment to disclosure and sharing by investigators, journals and funding agencies, and a recognition by the latter that, in many cases, ensuring reproducibility has a financial cost, that we will see better value for money from investment in model organism development and, in turn, a more robust translational pipeline.”

 Schofield, Ward, and Sundberg, 2016

 Improving reproducibility relies on thoroughly communicating the research methodologies—including the environmental factors—that may contribute to phenotypic variation. The Animal Research: Reporting of In Vivo Experiments ARRIVE Guidelines outline basic information needed about sample groups as well as key husbandry and housing parameters:

  1. Kilkenny, C., W. Browne, I. C. Cuthill, M. Emerson, D. G. Altman, and N. C3Rs Reporting Guidelines Working Group. 2010. “Animal research: reporting in vivo experiments: the ARRIVE guidelines,” Br J Pharmacol, 160: 1577-9. PMID: 20649561

For pathology studies, however, investigators need to consult an important extension of the ARRIVE guidelines, the Recommendations for Minimum Information for Publication of Experimental Pathology data, or MINPEPA, which are guidelines that offer a checklist for design and reporting of reproducible pathology datasets, including morphological, immunohistochemical and/or in situ hybridization studies:

  1. Scudamore, C. L., E. J. Soilleux, N. A. Karp, K. Smith, R. Poulsom, C. S. Herrington, M. J. Day, C. F. Brayton, B. Bolon, B. Whitelaw, E. S. White, J. I. Everitt, and M. J. Arends. 2016. “Recommendations for minimum information for publication of experimental pathology data: MINPEPA guidelines,” J Pathol, 238: 359-67. PMID: 26387837

References

Schofield, P. N., J. M. Ward, and J. P. Sundberg. 2016. 'Show and tell: disclosure and data sharing in experimental pathology', Dis Model Mech, 9: 601-5. PMID: 27483498 

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