Pathobiology of aging & age related diseases最新文献

{"title":"Rapamycin improves motor function, reduces 4-hydroxynonenal adducted protein in brain, and attenuates synaptic injury in a mouse model of synucleinopathy.","authors":"Xiang Bai, Margaret Chia-Ying Wey, Elizabeth Fernandez, Matthew J Hart, Jonathan Gelfond, Alex F Bokov, Sheela Rani, Randy Strong","doi":"10.3402/pba.v5.28743","DOIUrl":"10.3402/pba.v5.28743","url":null,"abstract":"<p><strong>Background: </strong>Synucleinopathy is any of a group of age-related neurodegenerative disorders including Parkinson's disease, multiple system atrophy, and dementia with Lewy Bodies, which is characterized by α-synuclein inclusions and parkinsonian motor deficits affecting millions of patients worldwide. But there is no cure at present for synucleinopathy. Rapamycin has been shown to be neuroprotective in several in vitro and in vivo synucleinopathy models. However, there are no reports on the long-term effects of RAPA on motor function or measures of neurodegeneration in models of synucleinopathy.</p><p><strong>Methods: </strong>We determined whether long-term feeding a rapamycin diet (14 ppm in diet; 2.25 mg/kg body weight/day) improves motor function in neuronal A53T α-synuclein transgenic mice (TG) and explored underlying mechanisms using a variety of behavioral and biochemical approaches.</p><p><strong>Results: </strong>After 24 weeks of treatment, rapamycin improved performance on the forepaw stepping adjustment test, accelerating rotarod and pole test. Rapamycin did not alter A53T α-synuclein content. There was no effect of rapamycin treatment on midbrain or striatal monoamines or their metabolites. Proteins adducted to the lipid peroxidation product 4-hydroxynonenal were decreased in brain regions of both wild-type and TG mice treated with rapamycin. Reduced levels of the presynaptic marker synaptophysin were found in several brain regions of TG mice. Rapamycin attenuated the loss of synaptophysin protein in the affected brain regions. Rapamycin also attenuated the loss of synaptophysin protein and prevented the decrease of neurite length in SH-SY5Y cells treated with 4-hydroxynonenal.</p><p><strong>Conclusion: </strong>Taken together, these data suggest that rapamycin, an FDA approved drug, may prove useful in the treatment of synucleinopathy.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"5 ","pages":"28743"},"PeriodicalIF":0.0,"publicationDate":"2015-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/83/f0/PBA-5-28743.PMC4549373.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34121746","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":"Geropathology Research Network Symposium 2015.","authors":"Warren Ladiges","doi":"10.3402/pba.v5.28866","DOIUrl":"https://doi.org/10.3402/pba.v5.28866","url":null,"abstract":"No abstract available. (Published: 1 July 2015) Citation: Pathobiology of Aging & Age-related Diseases 2015, 5 : 28866 - http://dx.doi.org/10.3402/pba.v5.28866 o abstract available.","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"5 ","pages":"28866"},"PeriodicalIF":0.0,"publicationDate":"2015-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/pba.v5.28866","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34259810","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 emerging role of senescent cells in tissue homeostasis and pathophysiology.","authors":"Kaoru Tominaga","doi":"10.3402/pba.v5.27743","DOIUrl":"https://doi.org/10.3402/pba.v5.27743","url":null,"abstract":"<p><p>Cellular senescence is a state of permanent growth arrest and is thought to play a pivotal role in tumor suppression. Cellular senescence may play an important role in tumor suppression, wound healing, and protection against tissue fibrosis in physiological conditions in vivo. However, accumulating evidence that senescent cells may have harmful effects in vivo and may contribute to tissue remodeling, organismal aging, and many age-related diseases also exists. Cellular senescence can be induced by various intrinsic and extrinsic factors. Both p53/p21 and p16/RB pathways are important for irreversible growth arrest in senescent cells. Senescent cells secret numerous biologically active factors. This specific secretion phenotype by senescent cells may largely contribute to physiological and pathological consequences in organisms. Here I review the molecular basis of cell cycle arrest and the specific secretion phenotype in cellular senescence. I also summarize the current knowledge of the role of cellular senescence in vivo in physiological and pathological settings. </p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"5 ","pages":"27743"},"PeriodicalIF":0.0,"publicationDate":"2015-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/pba.v5.27743","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33195619","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":"Animal models play a vital role in translational aging research.","authors":"Warren C Ladiges","doi":"10.3402/pba.v5.27702","DOIUrl":"https://doi.org/10.3402/pba.v5.27702","url":null,"abstract":"No abstract available. (Published: 17 March 2015) Citation: Pathobiology of Aging & Age-related Diseases 2015, 5 : 27702 - http://dx.doi.org/10.3402/pba.v5.27702","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"5 ","pages":"27702"},"PeriodicalIF":0.0,"publicationDate":"2015-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/pba.v5.27702","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33142818","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":"A model of chronic hepatitis in mice expressing a truncated XRCC1 protein.","authors":"Xuan Ge,&nbsp;Christina Pettan-Brewer,&nbsp;John Morton,&nbsp;Warren C Ladiges","doi":"10.3402/pba.v5.27703","DOIUrl":"https://doi.org/10.3402/pba.v5.27703","url":null,"abstract":"No abstract available. (Published: 17 March 2015) Citation: Pathobiology of Aging & Age-related Diseases 2015, 5 : 27703 - http://dx.doi.org/10.3402/pba.v5.27703","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"5 ","pages":"27703"},"PeriodicalIF":0.0,"publicationDate":"2015-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/pba.v5.27703","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33142819","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":"LINGO-1 promotes lysosomal degradation of amyloid-β protein precursor.","authors":"Rian de Laat,&nbsp;James S Meabon,&nbsp;Jesse C Wiley,&nbsp;Mark P Hudson,&nbsp;Thomas J Montine,&nbsp;Mark Bothwell","doi":"10.3402/pba.v5.25796","DOIUrl":"https://doi.org/10.3402/pba.v5.25796","url":null,"abstract":"<p><p>Sequential proteolytic cleavages of amyloid-β protein precursor (AβPP) by β-secretase and γ-secretase generate amyloid β (Aβ) peptides, which are thought to contribute to Alzheimer's disease (AD). Much of this processing occurs in endosomes following endocytosis of AβPP from the plasma membrane. However, this pathogenic mode of processing AβPP may occur in competition with lysosomal degradation of AβPP, a common fate of membrane proteins trafficking through the endosomal system. Following up on published reports that LINGO-1 binds and promotes the amyloidogenic processing of AβPP we have examined the consequences of LINGO-1/AβPP interactions. We report that LINGO-1 and its paralogs, LINGO-2 and LINGO-3, decrease processing of AβPP in the amyloidogenic pathway by promoting lysosomal degradation of AβPP. We also report that LINGO-1 levels are reduced in AD brain, representing a possible pathogenic mechanism stimulating the generation of Aβ peptides in AD. </p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"5 ","pages":"25796"},"PeriodicalIF":0.0,"publicationDate":"2015-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/pba.v5.25796","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33000718","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":"Zinc, aging, and immunosenescence: an overview.","authors":"Ángel Julio Romero Cabrera","doi":"10.3402/pba.v5.25592","DOIUrl":"https://doi.org/10.3402/pba.v5.25592","url":null,"abstract":"<p><p>Zinc plays an essential role in many biochemical pathways and participates in several cell functions, including the immune response. This review describes the role of zinc in human health, aging, and immunosenescence. Zinc deficiency is frequent in the elderly and leads to changes similar to those that occur in oxidative inflammatory aging (oxi-inflamm-aging) and immunosenescence. The possible benefits of zinc supplementation to enhance immune function are discussed. </p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"5 ","pages":"25592"},"PeriodicalIF":0.0,"publicationDate":"2015-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/pba.v5.25592","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33036857","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":"Planarians as a model of aging to study the interaction between stem cells and senescent cells in vivo","authors":"Patrick M. Perrigue, J. Najbauer, Agnieszka A. Jozwiak, J. Barciszewski, K. Aboody, M. Barish","doi":"10.3402/pba.v5.30052","DOIUrl":"https://doi.org/10.3402/pba.v5.30052","url":null,"abstract":"The depletion of stem cell pools and the accumulation of senescent cells in animal tissues are linked to aging. Planarians are invertebrate flatworms and are unusual in that their stem cells, called neoblasts, are constantly replacing old and dying cells. By eliminating neoblasts in worms via irradiation, the biological principles of aging are exposed in the absence of wound healing and regeneration, making planaria a powerful tool for aging research.","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89600415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolism and Aging: From Molecular Physiology to Systems Biology","authors":"W. Ladiges","doi":"10.3402/pba.v5.30765","DOIUrl":"https://doi.org/10.3402/pba.v5.30765","url":null,"abstract":"No abstract available. Citation: Pathobiology of Aging & Age-related Diseases 2015, 5: 30765 - http://dx.doi.org/10.3402/pba.v5.30765","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91361082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An immunohistochemical approach for monitoring effects of exercise on tumor stromal cells in old mice.","authors":"Christina Pettan-Brewer, Jorming Goh, Warren C Ladiges","doi":"10.3402/pba.v4.24824","DOIUrl":"10.3402/pba.v4.24824","url":null,"abstract":"<p><p>Epidemiological evidence supports a protective effect of physical activity for breast cancer in older women, but the mechanisms are not well understood. We used 18-month-old BALB/c mice injected in the mammary fat pad with syngeneic 4T1 tumor cells as a model of invasive breast cancer. During the tumor progression phase, there was a significant decrease in labeling for F4/80, a marker for mouse macrophages, and CD34, a marker for vascular endothelial cells, in primary tumors from mice that ran higher average distances compared to mice that ran lower average distances (p≤0.05). These observations suggest that immunohistochemistry can be used to monitor stromal cell populations in tumors from old mice under exercise conditions. </p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/83/ea/PBA-4-24824.PMC4131002.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32606094","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}