title: A new murine model of aging lung: the senescence accelerated mouse (SAM)-P.
abstract: The senescence accelerated mouse (SAM) has recently been characterized as a unique model to investigate age-related disorders, including amyloidosis, cataract, osteoporosis and dementia. However, little is known as to the properties of the lung in these animals. Tobacco smoke is also associated with enhanced loss of elastic recoil and the development of emphysema. We have attempted to examine morphological as well as biochemical changes of the distal lung in SAM-P/2, as the senescence-prone series and SAM-R/1, as the senescence-resistant series. The animals were intermittently exposed to tobacco smoke or air by Hamburg II machines for 5 weeks. Then both groups of animals were killed for histologic and biochemical study. Compared with SAM-R/1, SAM-P/2, even with air exposure, showed a higher value of the mean linear intercept without alveolar wall destruction. It became even greater due to tobacco exposure with emphysematous change. Tobacco exposure accumulated inflammatory cells into alveoli in SAM-P/2, but not in SAM-R/1. Oxygen radical generation by those cells was also higher in SAM-P/2. Analysis of bronchoalveolar lavage fluid in SAM-P/2 after tobacco exposure disclosed increases in albumin content, total protein content and elastase-like activity. There were decreases in the ratio of elastase inhibitory capacity (EIC) to trypsin inhibitory capacity (TIC), contents of glutathione and total free thiol groups. Moreover, SAM-P/2 showed significantly lower EIC/TIC ratio in serum, even with air exposure, than that of SAM-R/1. These results indicate that SAM-P/2 can be a good model for the study of natural evolution of the aging lung as well as its susceptibility to tobacco smoke in the development of emphysema.
authors.affiliation: Department of Geriatrics, Tokyo University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Uejima
authors.forename: Y
authors.initials: Y
authors.lastname: Fukuchi
authors.forename: T
authors.initials: T
authors.lastname: Nagase
authors.forename: R
authors.initials: R
authors.lastname: Tabata
authors.forename: H
authors.initials: H
authors.lastname: Orimo
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism / Q000473:pathology; D004646:Emphysema / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005609:Free Radicals; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D012907:Smoking / Q000378:metabolism / Q000473:pathology; D014361:Trypsin Inhibitors / Q000378:metabolism
chemical_list: D005609:Free Radicals; D014361:Trypsin Inhibitors; D010196:Pancreatic Elastase; D010100:Oxygen