title: Influence of Chronic Exposure to Simulated Shift Work on Disease and Longevity in Disease-Prone Inbred Mice.
abstract: Shift work (SW) is viewed as a risk factor for the development of many serious health conditions, yet prospective studies that document such risks are rare. The current study addressed this void by testing the hypothesis that long-term exposure to repeated diurnal phase shifts, mimicking SW, will accelerate disease onset or death in inbred mice with genetic risk of developing cancer, diabetes, or autoimmune disease. The data indicate that 1) life-long exposure to simulated SW accelerates death in female cancerprone AKR/J mice; 2) a significant proportion of male NON/ShiLtJ mice, which have impaired glucose tolerance but do not normally progress to type 2 diabetes, develop hyperglycemia, consistent with diabetes (that is, blood glucose 250 mg/dL or greater) after exposure to simulated SW for 8 wk; and 3) MRL/MpJ mice, which are prone to develop autoimmune disease, showed sex-related acceleration of disease development when exposed to SW as compared with mice maintained on a stable photocycle. Thus, longterm exposure to diurnal phase shifts that mimic SW reduces health or longevity in a wide variety of disease models. Our approach provides a simple way to assess the effect of chronic diurnal disruption in disease development in at-risk genotypes.
authors.affiliation: Departments of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois;, Email: toth.linda@frontier.com.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Toth
authors.affiliation: Departments of Internal Medicine, Southern Illinois University School of Medicine, Springfield, Illinois.
authors.forename: Rita A
authors.initials: RA
authors.lastname: Trammell
authors.affiliation: Departments of Internal Medicine, Southern Illinois University School of Medicine, Springfield, Illinois.
authors.forename: Teresa
authors.initials: T
authors.lastname: Liberati
authors.affiliation: Departments of Medical Microbiology, Immunology, and Cell Biology, Southern Illinois University School of Medicine, Springfield, Illinois.
authors.forename: Steve
authors.initials: S
authors.lastname: Verhulst
authors.affiliation: Comparative Medicine Program, Department of Veterinary Pathology, University of Missouri, Columbia, Missouri.
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Hart
authors.affiliation: Comparative Medicine Program, Department of Veterinary Pathology, University of Missouri, Columbia, Missouri.
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Moskowitz
authors.affiliation: Comparative Medicine Program, Department of Veterinary Pathology, University of Missouri, Columbia, Missouri.
authors.forename: Craig
authors.initials: C
authors.lastname: Franklin
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000473:pathology; D001786:Blood Glucose; D002940:Circadian Rhythm; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006943:Hyperglycemia / Q000473:pathology; D008136:Longevity; D008297:Male; D008815:Mice, Inbred Strains; D009369:Neoplasms / Q000473:pathology; D017440:Photoperiod; D000073577:Shift Work Schedule
chemical_list: D001786:Blood Glucose