Hutchinson-Gilford Progeria Syndrome (HGPS) is a devastating premature aging 
disease. Mouse models have been instrumental for understanding HGPS mechanisms 
and for testing therapies, which to date have had only marginal benefits in mice 
and patients. Barriers to developing effective therapies include the unknown 
etiology of progeria mice early death, seemingly unrelated to the reported 
atherosclerosis contributing to HGPS patient mortality, and mice not 
recapitulating the severity of human disease. Here, we show that progeria mice 
die from starvation and cachexia. Switching progeria mice approaching death from 
regular diet to high-fat diet (HFD) rescues early lethality and ameliorates 
morbidity. Critically, feeding the mice only HFD delays aging and nearly doubles 
lifespan, which is the greatest lifespan extension recorded in progeria mice. 
The extended lifespan allows for progeria mice to develop degenerative aging 
pathologies of a severity that emulates the human disease. We propose that 
starvation and cachexia greatly influence progeria phenotypes and that 
nutritional/nutraceutical strategies might help modulate disease progression. 
Importantly, progeria mice on HFD provide a more clinically relevant animal 
model to study mechanisms of HGPS pathology and to test therapies.