title: Quantitative proteomics of rat livers shows that unrestricted feeding is stressful for proteostasis with implications on life span.
abstract: Studies in young mammals on the molecular effects of food restriction leading to prolong adult life are scares. Here, we used high-throughput quantitative proteomic analysis of whole rat livers to address the molecular basis for growth arrest and the apparent life-prolonging phenotype of the food restriction regimen. Over 1800 common proteins were significantly quantified in livers of ad libitum, restriction- and re-fed rats, which summed up into 92% of the total protein mass of the cells. Compared to restriction, ad libitum cells contained significantly less mitochondrial catabolic enzymes and more cytosolic and ER HSP90 and HSP70 chaperones, which are hallmarks of heat- and chemically-stressed tissues. Following re-feeding, levels of HSPs nearly reached ad libitum levels. The quantitative and qualitative protein values indicated that the restriction regimen was a least stressful condition that used minimal amounts of HSP-chaperones to maintain optimal protein homeostasis and sustain optimal life span. In contrast, the elevated levels of HSP-chaperones in ad libitum tissues were characteristic of a chronic stress, which in the long term could lead to early aging and shorter life span.
authors: The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center, Petach Tikva, Israel.|Felsenstein Medical Research Center, Petach Tikva, Israel.|Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.
authors: Galia
authors: G
authors: Gat-Yablonski
authors: Department of Plant Molecular Biology, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland.|Department of Ecology, Agronomy and Aquaculture, University of Zadar, 23000 Zadar, Croatia.
authors: Andrija
authors: A
authors: Finka
authors: Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.
authors: Galit
authors: G
authors: Pinto
authors: Protein Analysis Facility, University of Lausanne, 1015 Lausanne, Switzerland.
authors: Manfredo
authors: M
authors: Quadroni
authors: Felsenstein Medical Research Center, Petach Tikva, Israel.|Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.
authors: Biana
authors: B
authors: Shtaif
authors: Department of Plant Molecular Biology, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland.
authors: Pierre
authors: P
authors: Goloubinoff
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D004435:Eating / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology; D005508:Food Deprivation; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D008136:Longevity / Q000502:physiology*; D040901:Proteomics; D051381:Rats
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins
keywords: aging; catch up growth; food restriction; heat shock proteins; mitochondria