Doubled lifespan and patient‐like pathologies in progeria mice fed high‐fat diet
Autor: | Cyrielle Billon, Thomas P. Burris, David A. Ford, Ángel Baldán, Zacharie Toth, Andrew A. Butler, Susana Gonzalo, Carolyn J. Albert, Sara McBride-Gagyi, Ray Kreienkamp, Gonzalo Bedia-Diaz |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Premature aging Aging congenital hereditary and neonatal diseases and abnormalities media_common.quotation_subject Longevity Disease Biology Bioinformatics Diet High-Fat Cachexia 03 medical and health sciences 0302 clinical medicine Progeria medicine Animals Humans media_common 2. Zero hunger Starvation Original Paper integumentary system nutritional and metabolic diseases High fat diet Cell Biology Feeding Behavior medicine.disease Lamin Type A Original Papers 3. Good health Mice Inbred C57BL 030104 developmental biology Phenotype Mutation Etiology medicine.symptom 030217 neurology & neurosurgery |
Zdroj: | Aging Cell |
ISSN: | 1474-9726 1474-9718 |
Popis: | 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. |
Databáze: | OpenAIRE |
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