: Phenotypic analysis of progeroid mice under dietary restriction and pharmacological interventions.
i. Objective of research: To identify key mechanisms and of key components that can be targeted pharmacologically to promote health.
ii. Current state of the art: Reduced activity of the nutrient-sensing signaling network extends healthy lifespan in diverse organisms, possible including humans. A key objective is to identify the mechanisms that promote health, in order to target them pharmacologically to prevent human ageing-related diseases.
iii. Research methodology and approach: Our ESR will take advantage of the mouse models of premature ageing generated in our laboratory. These mutant mice will be essential to identify mechanisms that promote health and ageing, and to evaluate pharmacological strategies to prevent human ageing-related diseases. Our ESR will work on processes downstream of the IIS pathway and in tissues other than skeletal and heart muscle to identify the impact of muscle cells and tissue on organismal longevity. Our ESR will also investigate systemic factors, which will also be assessed for suitability as biomarkers, to validate the role of NFkB and other signaling pathways as intervention targets.
iv. Originality and innovative aspects of the ESR project: The use of animal models will allow the student to identify those systemic factors suitable to be targeted pharmacologically. Also, the use of progeroid mice models will drastically shorten the length of the studies, so that the student can obtain enough data within the fellowship period. Moreover, the experiments with mouse models will be complemented with cell culture experiments that imply the use of innovative technologies such as CRISPR-Cas9 modification of the genome or iPS cells generation.
v. Integration of the ESR project to the overall research programme: Our ESR will work with the Schumacher group to measure cellular senescence, with ProtATonce on identifying age-related biomarkers and with the Scorrano and the Garinis group for the integrated analysis of organismal DNA damage responses.