WG2 - Models
Leader: Dr Paul Potter
Testing interventions in mice is an important step in the drug development process for age-related diseases. Regulatory requirements almost always call for definitive studies in at least two laboratory animal species, one of which is rodent. Despite differences between humans and mice in metabolism, lifespan and susceptibility to diseases, murine models have proven to be a valuable aid to understanding the biology of ageing. They have also been key indetermining the impact of interventions on lifespan, healthspan and frailty in a mammalian physiology, a critical step for translation into the clinic. This is because mice are relatively economical, require lower drug dosages and there is a huge volume of supporting literature on their genetics and genomics, physiology, behaviour and biochemistry.
The choice of animal model in which to accurately assess healthspan and frailty also requires careful consideration. At present the common practice is either to extrapolate data obtained from interventions in genetically homogeneous animal models or in disease models that develop the condition early in life. There are several European programmes such as EUMORPHIA, EUMODIC, and Infrafrontier, all targeting the generation and phenotypic analysis of knock out mouse mutants as models of disease but there has been little or no work to test the effect of age on disease development.
The aims of the work group are to:
- Review models of ageing and age-related diseases and identify gaps where new or modified models are required to be developed.
- Create a publicly available web-based database which centralises all existing resources (including existing models), and acts as reference point for all researchers of ageing undertaking preclinical work.
Progress to date:
- Training school completed, 2015 (Creating and Phenotyping Mouse models of Disease and Ageing).
- Reviewed existing models of age and age-related diseases
- Initiated database
- Identified gaps in models of multimorbidity. Models of age-related diseases are mostly in young mice and acute, generally with limited phenotypic analysis of a few tissues or organs. There is a need of models which develop less aggressive and more chronic disease with age analysed across a range of physiological systems to better reflect the situation seen in patients
- A review on models of resilience is ongoing
Susanne Drechsler, Marina A Lynch, Susana Novella, Herminia González-Navarro, Silva Hecimovic, Erica Barini and Valter Tucci, Rui E Castro, Roosmarijn E. Vandenbroucke, Marcin Osuchowski, Paul K. Potter. 2016. With mouse age comes wisdom: a review and suggestions of relevant mouse models for age-related changes and diseases. Mechanisms of Ageing and Development, 160, 54-68.
Sulev Kõks, Soner Dogan, Bilge Guvenc Tuna, Herminia González-Navarro, Paul Potter, Roosmarijn E. Vandenbroucke. 2016. Mouse Models of Ageing and their relevance to disease. Mechanisms of Ageing and Development, 160, 41-53.