Pathobiology of aging & age related diseases最新文献

{"title":"Broad segmental progeroid changes in short-lived Ercc1(-/Δ7) mice.","authors":"Martijn E T Dollé,&nbsp;Raoul V Kuiper,&nbsp;Marianne Roodbergen,&nbsp;Joke Robinson,&nbsp;Sisca de Vlugt,&nbsp;Susan W P Wijnhoven,&nbsp;Rudolf B Beems,&nbsp;Liset de la Fonteyne,&nbsp;Piet de With,&nbsp;Ingrid van der Pluijm,&nbsp;Laura J Niedernhofer,&nbsp;Paul Hasty,&nbsp;Jan Vijg,&nbsp;Jan H J Hoeijmakers,&nbsp;Harry van Steeg","doi":"10.3402/pba.v1i0.7219","DOIUrl":"https://doi.org/10.3402/pba.v1i0.7219","url":null,"abstract":"<p><p>Genome maintenance is considered a prime longevity assurance mechanism as apparent from many progeroid human syndromes that are caused by genome maintenance defects. The ERCC1 protein is involved in three genome maintenance systems: nucleotide excision repair, interstrand cross-link repair, and homologous recombination. Here we describe in-life and post-mortem observations for a hypomorphic Ercc1 variant, Ercc1(-/Δ7), which is hemizygous for a single truncated Ercc1 allele, encoding a protein lacking the last seven amino acids. Ercc1(-/Δ7) mice were much smaller and median life span was markedly reduced compared to wild-type siblings: 20 and 118 weeks, respectively. Multiple signs and symptoms of aging were found to occur at an accelerated rate in the Ercc1(-/Δ7) mice as compared to wild-type controls, including a decline in weight of both whole body and various organs, numerous histopathological lesions, and immune parameters. Together they define a segmental progeroid phenotype of the Ercc1(-/Δ7) mouse model.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/pba.v1i0.7219","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30885937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mouse as a model for understanding chronic diseases of aging: the histopathologic basis of aging in inbred mice.","authors":"John P Sundberg, Annerose Berndt, Beth A Sundberg, Kathleen A Silva, Victoria Kennedy, Roderick Bronson, Rong Yuan, Beverly Paigen, David Harrison, Paul N Schofield","doi":"10.3402/pba.v1i0.7179","DOIUrl":"10.3402/pba.v1i0.7179","url":null,"abstract":"<p><p>Inbred mice provide a unique tool to study aging populations because of the genetic homogeneity within an inbred strain, their short life span, and the tools for analysis which are available. A large-scale longitudinal and cross-sectional aging study was conducted on 30 inbred strains to determine, using histopathology, the type and diversity of diseases mice develop as they age. These data provide tools that when linked with modern in silico genetic mapping tools, can begin to unravel the complex genetics of many of the common chronic diseases associated with aging in humans and other mammals. In addition, novel disease models were discovered in some strains, such as rhabdomyosarcoma in old A/J mice, to diseases affecting many but not all strains including pseudoxanthoma elasticum, pulmonary adenoma, alopecia areata, and many others. This extensive data set is now available online and provides a useful tool to help better understand strain-specific background diseases that can complicate interpretation of genetically engineered mice and other manipulatable mouse studies that utilize these strains.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/de/94/PBA-1-7179.PMC3417678.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30885939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathobiology of aging: an old problem gets a new look.","authors":"Warren Ladiges","doi":"10.3402/pba.v1i0.7281","DOIUrl":"https://doi.org/10.3402/pba.v1i0.7281","url":null,"abstract":"The pursuit of investigations into the science of aging is really designed to understand why cellular processes begin to fail with advancing age, and what molecular events contribute to this failure. In this regard, the distinction between aging and the diseases associated with aging becomes less clear, and they are most likely driven by the same or similar events related to biological decline. With the launch of Pathobiology of Aging & Age-related Diseases, we hope to enlighten the scientific community by recognizing outstanding pathobiology-based scientific contributions, allowing scientists to communicate data that might be of less interest in other journals more focused on generic aging or specific scientific disciplines. Aging is indeed an ‘old’ problem and is being studied in a variety of ways that use mammalian model systems to identify mechanistic pathways that can be targeted to maintain healthy living. In this regard, we are providing a ‘new’ venue for disseminating information that specifically focuses on the pathobiological aspects of aging and the chronic diseases directly associated with aging. There will be a commitment to publishing manuscripts that meet the highest standards of science, but the nature of the journal will allow highly detailed and image-intensive descriptions of the pathology of aging and disease conditions associated with aging. The aim is to provide an interdisciplinary venue for pathology-based manuscripts that focus on the physiological function of aging in preclinical mammalian models. (Published: 1 June 2011) Citation: Pathobiology of Aging & Age-related Diseases 2011, 1 : 7281 - DOI: 10.3402/pba.v1i0.7281","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/pba.v1i0.7281","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30885935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The anti-tumor effects of calorie restriction are correlated with reduced oxidative stress in ENU-induced gliomas.","authors":"Megan A Mahlke,&nbsp;Lisa A Cortez,&nbsp;Melanie A Ortiz,&nbsp;Marisela Rodriguez,&nbsp;Koji Uchida,&nbsp;Mark K Shigenaga,&nbsp;Shuko Lee,&nbsp;Yiquang Zhang,&nbsp;Kaoru Tominaga,&nbsp;Gene B Hubbard,&nbsp;Yuji Ikeno","doi":"10.3402/pba.v1i0.7189","DOIUrl":"https://doi.org/10.3402/pba.v1i0.7189","url":null,"abstract":"<p><p>The anti-tumor effects of calorie restriction (CR) and the possible underlying mechanisms were investigated using ethylnitrosourea (ENU)-induced glioma in rats. ENU was given transplacentally at gestational day 15, and male offspring were used in this experiment. The brain from 4-, 6-, and 8-month-old rats fed either ad libitum (AL) or calorie-restricted diets (40% restriction of total calories compared to AL rats) was studied. Tumor burden was assessed by comparing the number and size of gliomas present in sections of the brain. Immunohistochemical analysis was used to document lipid peroxidation [4-hydroxy-2-nonenal (HNE) and malondialdehyde (MDA)], protein oxidation (nitrotyrosine), glycation and AGE formation [methylglyoxal (MG) and carboxymethyllysine (CML)], cell proliferation activity [proliferating cell nuclear antigen (PCNA)], cell death [single-stranded DNA (ssDNA)], presence of thioredoxin 1 (Trx1), and presence of heme oxygenase-1 (HO-1) associated with the development of gliomas. The results showed that the number of gliomas did not change with age in the AL groups; however, the average size of the gliomas was significantly larger in the 8-month-old group compared to that of the younger groups. Immunopositivity was observed mainly in tumor cells and reactive astrocytes in all histological types of ENU-induced glioma. Immunopositive areas for HNE, MDA, nitrotyrosine, MG, CML, HO-1, and Trx1 increased with the growth of gliomas. The CR group showed both reduced number and size of gliomas, and tumors exhibited less accumulation of oxidative damage, decreased formation of glycated end products, and a decreased presence of HO-1 and Trx1 compared to the AL group. Furthermore, gliomas of the CR group showed less PCNA positive and more ssDNA positive cells, which are correlated to the retarded growth of tumors. Interestingly, we also discovered that the anti-tumor effects of CR were associated with decreased hypoxia-inducible factor-1α (HIF-1α) levels in normal brain tissue. Our results are very exciting because they not only demonstrate the anti-tumor effects of CR in gliomas, but also indicate the possible underlying mechanisms, i.e. anti-tumor effects of CR observed in this investigation are associated with reduced accumulation of oxidative damage, decreased formation of glycated end products, decreased presence of HO-1 and Trx1, reduced cell proliferation and increased apoptosis, and decreased levels of HIF-1α.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/pba.v1i0.7189","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30885938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin suppresses intestinal polyps in APC Min mice fed a high fat diet.","authors":"Christina Pettan-Brewer,&nbsp;John Morton,&nbsp;Ruby Mangalindan,&nbsp;Warren Ladiges","doi":"10.3402/pba.v1i0.7013","DOIUrl":"https://doi.org/10.3402/pba.v1i0.7013","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a leading cause of cancer deaths in the United States. Various risk factors have been associated with CRC including increasing age and diet. Epidemiological and experimental studies have implicated a diet high in fat as an important risk factor for colon cancer. High fat diets can promote obesity resulting in insulin resistance and inflammation and the development of oxidative stress, increased cell proliferation, and suppression of apoptosis. Because of the high consumption of dietary fats, especially saturated fats, by Western countries, it is of interest to see if non-nutrient food factors might be effective in preventing or delaying CRC in the presence of high saturated fat intake. Curcumin (Curcuma longa), the main yellow pigment in turmeric, was selected to test because of its reported anti-tumor activity. APC Min mice, which develop intestinal polyps and have many molecular features of CRC, were fed a diet containing 35% pork fat, 33% sucrose, and a protein and vitamin mineral mixture (HFD) with or without 0.5% curcumin. These cohorts were compared to APC Min mice receiving standard rodent chow (RC) with 8% fat. APC Min mice fed the HFD for 3 months had a 23% increase in total number of polyps compared to APC Min mice on RC. Curcumin was able to significantly reverse the accelerated polyp development associated with the HFD suggesting it may be effective clinically in helping prevent colon cancer even when ingesting high amounts of fatty foods. The anti-tumor effect of curcumin was shown to be associated with enhanced apoptosis and increased efficiency of DNA repair. Since curcumin prevented the gain in body weight seen in APC Min mice ingesting the HFD, modulation of energy metabolism may also be a factor.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/pba.v1i0.7013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30885934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical pathology of aging mice.","authors":"Christina Pettan-Brewer,&nbsp;Piper M Treuting","doi":"10.3402/pba.v1i0.7202","DOIUrl":"https://doi.org/10.3402/pba.v1i0.7202","url":null,"abstract":"<p><p>Old mice will have a subset of lesions as part of the progressive decline in organ function that defines aging. External and palpable lesions will be noted by the research, husbandry, or veterinary staff during testing, cage changing, or physical exams. While these readily observable lesions may cause alarm, not all cause undue distress or are life-threatening. In aging research, mice are maintained until near end of life that, depending on strain and genetic manipulation, can be upwards of 33 months. Aging research has unique welfare issues related to age-related decline, debilitation, fragility, and associated pain of chronic diseases. An effective aging research program includes the collaboration and education of the research, husbandry, and veterinary staff, and of the members of the institution animal care and use committee. This collaborative effort is critical to humanely maintaining older mice and preventing excessive censorship due to non-lethal diseases. Part of the educational process is becoming familiar with how old mice appear clinically, at necropsy and histopathologically. This baseline knowledge is important in making the determination of humane end points, defining health span, contributing causes of death and effects of interventions. The goal of this paper is to introduce investigators to age-associated diseases and lesion patterns in mice from clinical presentation to pathologic assessment. To do so, we present and illustrate the common clinical appearances, necropsy and histopathological lesions seen in subsets of the aging colonies maintained at the University of Washington.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/pba.v1i0.7202","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30885940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}