Does age matter? The impact of rodent age on study outcomes (1)
The quality of data obtained from rodent models and these factors differ according to the requirements of the experiment. Animal experiments in peer-reviewed publications is sometime poor due to omission of details of experimental design such as blinding, randomization, and details of strain, sex and age. Significant differences exist in disease-relevant systems in young or aged animals compared with middle-aged counterparts, and these differences may affect the outcome of studies investigating basic disease biology, mechanisms of drug action and efficacy.
The age at which animal models are commonly used is 8–12 weeks. In this age range, many developmental processes are ongoing, 6–11 and changes in physiology with age may have a large impact on experimental variables.
B-cells have an immature phenotype until four weeks of age, T-cell responses mature around eight weeks of age, and T and B-lymphocyte production increases over the first 26 weeks of life. The microbiome plays important roles in the maintenance of appropriate immune system function and response to disease. Ageing can affect the composition of the mouse microbiome, and this has been shown to modulate mouse models of allergic airway
disease, potentially reducing the quality of data obtained.
Researchers in different laboratories used different ages of animal in the same experimental paradigm.
The age range over which the term ‘adult’ was applied across these responses was 6–20 weeks. This illustrates the potential discrepancy when using general descriptions of rodent age.
The age used varied over a range of up to 20 weeks. This discrepancy in the age of animal used between different laboratories using the same model could lead to data variability obtained between those laboratories. This illustrates the importance of using standardized or consensus protocols, and designing experiments with reference to published work on the biology of the system being studied.
The definition of ‘adult’ in this context is likely to be related to the sexual maturity of the rodent. Indeed, rodents are sexually mature and able to breed from around five weeks of age. Many systems are immature at this age and may take weeks or months to develop to maturity.
One study defined a mature adult C57BL6/J mouse as 3–6 months (equivalent in this analysis to 20–30 human years), a middle-aged mouse as 10–14 months (equivalent to 38–47 human years) and an old mouse as 18–24 months (equivalent to 56–69 human years). Using this approach, 12 weeks should be the minimum for a model of adult disease.