WG1 - Definition of Variables, Endpoints, Methods of Assessments
Leader: Anne-Ulrike Trendelenburg
Translating interventions from research to approved medicine is a long term process (average 17 years). To increase success rate, it is very important to develop translatable disease models and readouts as close as possible to the clinic. They have to be objective, robust and consistent outcomes, assessable in mice, reflecting clinically relevant measures applicable to human trials. This is particularly important for geroprotectors since aging is a multi-factorial syndrome and many different organ systems are affected.
Currently, there are gaps in knowledge and communication between scientists in preclinical phase, geriatricians, industrial partners and regulatory bodies, are a barrier to the identification of relevant validated outcome measures. For example, endpoints such as healthspan and frailty are used in clinical research to monitor interventions. In contrast, most studies in mice focus on lifespan. Ways to assess healthspan and frailty in mice are just starting to evolve and while measuring lifespan may be important, it is not the measurement of effectiveness which is useful for clinical translation. Therefore, a more translational approach of mouse aging studies should involve endpoints related to human healthy aging.
WG1 aims to:
- Review definitions of frailty in mice an ways to assess it resembling frailty assessment in humans as much as possible
- Identify mechanisms of ageing, pathways and potential target for biomarkers underlining frailty to monitor (early stages of) interventions
Progress to date:
- Frailty has been defined as an accumulation of deficits leading to increased vulnerability to adverse health outcomes
- A review on approaches to measure frailty in mice has been undertaken and can be found here (Frailty in mouse ageing: A conceptual approach)
- A second review on mechanisms, pathways and targets for biomarkers can be found at: https://www.ncbi.nlm.nih.gov/pubmed/30071357