Progressing the care, husbandry and management of ageing mice used in scientific studies.

Driven by the longer lifespans of humans, particularly in Westernised societies, and the need to know more about 'healthy ageing', ageing mice are being used increasingly in scientific research. Many departments and institutes involved with ageing research have developed their own systems to determine intervention points for potential refinements and to identify humane end points. Several good systems are in use, but variations between them could contribute to poor reproducibility of the science achieved. Working with scientific and regulatory communities in the UK, we have reviewed the clinical signs observed in ageing mice and developed recommendations for enhanced monitoring, behaviour assessment, husbandry and veterinary interventions. We advocate that the default time point for enhanced monitoring should be 15 months of age, unless prior information is available. Importantly, the enhanced monitoring should cause no additional harms to the animals. Where a mouse strain is well characterised, the onset of age-related enhanced monitoring may be modified based on knowledge of the onset of an expected age-related clinical sign. In progeroid models where ageing is accelerated, enhanced monitoring may need to be brought forward. Information on the background strain must be considered, as it influences the onset of age-related clinical signs. The range of ageing models currently used means that there will be no 'one-size fits all' solution. Increased awareness of the issues will lead to more refined and consistent husbandry of ageing mice, and application of humane end points will help to reduce the numbers of animals maintained for longer than is scientifically justified.