Liver senescence integrates the hallmarks of aging – LiverSenes

Aging is characterized by a progressive loss of physiological integrity, leading to age associated frailty. The hallmarks of aging include cellular senescence, telomere attrition and metabolic disorders. Remarkably, during aging the liver is one of the first organs displaying these particular traits. In this project, we propose to use complementary expertise and models to explore the interdependence of these different traits of aging. We propose liver senescence as a key hub, and an entry point to a deleterious cascade leading to age related dysfunctions. To this purpose we will test the sufficiency and necessity of telomere attrition and metabolic alterations as potential modulators of senescence in the liver of mouse and zebrafish. The results from our work will help to decipher the chronology of events starting in the liver and leading to the whole-body aging and will help to better design and refine therapeutic strategies.