Journal of the American Aging Association最新文献

{"title":"31st Annual meeting of the American Aging Association, 16th annual meeting of the American College of Clinical Geronotology","authors":"","doi":"10.1007/s11357-002-0012-1","DOIUrl":"https://doi.org/10.1007/s11357-002-0012-1","url":null,"abstract":"","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"25 1","pages":"131-148"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-002-0012-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52978676","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 hypothesis concerning control networks and aging in Drosophila melanogaster and Caenorhabditis elegans.","authors":"C Driver","doi":"10.1007/s11357-001-0018-0","DOIUrl":"https://doi.org/10.1007/s11357-001-0018-0","url":null,"abstract":"<p><p>To explain trends emerging from the study of longevity mutants, a modification of the reactive oxygen species (ROS) model of aging is suggested. ROS do not appear to be produced in greater quantities during cellular activity unless specific factors are also present. These include raised cytosolic calcium and sodium ions, nitric oxide (NO) or dopamine. Metabolically active cells that are repeatedly exposed to these factors, especially in combination, show the most ROS damage and may contribute most to aging. This explains the importance of neurons, which is highlighted by genetic studies, and points to which cells are the most aging-sensitive. Control pathways disrupted in long-lived mutants are those which control one or more of these ROS promoting factors. The daf-2/daf-16 pathway may interact with these factors in several ways. Changes in control networks may be propagated from a relatively small number of cells/junctions by neural connectivity and hormonal means.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"24 4","pages":"173-7"},"PeriodicalIF":0.0,"publicationDate":"2001-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-001-0018-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31466775","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":"Role of xanthine dehydrogenase and aging on the innate immune response of Drosophila.","authors":"Y S Kim,&nbsp;H J Nam,&nbsp;H Y Chung,&nbsp;N D Kim,&nbsp;J H Ryu,&nbsp;W J Lee,&nbsp;R Arking,&nbsp;M A Yoo","doi":"10.1007/s11357-001-0020-6","DOIUrl":"https://doi.org/10.1007/s11357-001-0020-6","url":null,"abstract":"<p><p>It has been proposed that uric acid is an important scavenger of deleterious oxygen species and peroxynitrite in biological systems. The cellular sources responsible for the generation of damage-causing reactive oxygen species (ROS) are widespread. Xanthine dehydrogenase (XDH) / oxidase (XOD) catalyzes the oxidation of xanthine to uric acid. The rosy (ry) gene encodes XDH/XOD in Drosophila melanogaster. XDH codes for uric acid which is a ROS scavenger. XOD however is an enzyme system implicated in ROS production. In this study, we investigated the roles of XDH in the fly's immune defense response to infection and in the aging process. We first compared ROS generation and nitric oxide (NO) level in the whole body and the gut of XDH mutant with those of wild type. Our results suggested that XDH has a protective effect with respect to both ROS and NO generations, particularly in the gut. We also examined the effect of a XDH deletion mutant on the relative sensitivity of the organism against bacterial infection, on the immune inducibility of antimicrobial peptides and on the effect of aging in the defensive response to infection. Our results strongly suggest that XDH plays an important role in the innate immune response and that the age-associated deterioration of the innate immune response might be, at least in part, associated with the loss of XDH activity in the aging process.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"24 4","pages":"187-93"},"PeriodicalIF":0.0,"publicationDate":"2001-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-001-0020-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31466777","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 effect of lipopolysaccharide on enhanced inflammatory process with age: Modulation of NF-κB.","authors":"H J Kwon,&nbsp;B K Sung,&nbsp;J W Kim,&nbsp;J H Lee,&nbsp;N D Kim,&nbsp;M A Yoo,&nbsp;H S Kang,&nbsp;H S Baek,&nbsp;S J Bae,&nbsp;J S Choi,&nbsp;R Takahashi,&nbsp;S Goto,&nbsp;H Y Chung","doi":"10.1007/s11357-001-0017-1","DOIUrl":"https://doi.org/10.1007/s11357-001-0017-1","url":null,"abstract":"<p><p>Oxidative stress is thought to be a causative factor for age-related damage in a wide variety of cellular constituents that can lead to dysfunction and various pathological conditions, including the inflammatory process. At the molecular level, the redox-sensitive transcription factor, NF-κB plays a key role in the regulation of the inflammatory process, along with cytokines, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). We studied the mechanism underlying the modulation of the inflammatory reaction with age by investigating NF-κB activation and the expression of COX-2, iNOS, and cytokines genes in hepatic tissues isolated from young and old rats. We expanded our investigation of these factors in rats injected with the inflammatory activator, lipopolysaccharide (LPS). Data showed that NF-κB activity was up-regulated with age and was further enhanced by LPS injection, indicating an increased susceptibility and sensitivity to the inflammatory stimulus with age. To explore further the molecular events leading to NF-κB activation, we investigated the inhibitory component of NF-κB complex, IκB. Cytosolic IκBα, but not IκBβ, was significantly decreased in both old and LPS-treated rats, signifying the enhanced migration of cytosolic NF-κB complex into the nucleus following dissociation from the inhibitor. The appearance of the polypeptide, p65, as determined in the nucleus, corresponded with the change in IκBα, providing further supporting evidence for the molecular process involved in NF-κB activation. Our additional investigation of two proinflammatory-related enzymes, COX-2 and iNOS, and three cytokines, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α, clearly showed aged-related increases, in corroboration with the NF-κB activation. Our results demonstrated that LPS injection caused the enhanced gene expression of inducible proinflammatory proteins, COX-2 and iNOS through NF-κB activation.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"24 4","pages":"163-71"},"PeriodicalIF":0.0,"publicationDate":"2001-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-001-0017-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31466774","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":"Life span extensions associated with upregulation of gene expression of antioxidant enzymes in Caenorhabdms elegans; studies of mutation in the AGE-1, PI3 kinase homologue and short-term exposure to hyperoxia.","authors":"Y Honda,&nbsp;S Honda","doi":"10.1007/s11357-001-0019-z","DOIUrl":"https://doi.org/10.1007/s11357-001-0019-z","url":null,"abstract":"<p><p>Life span could be modified by genetic or environmental perturbations in Caenorhabditis elegans. Here we show that two extensions of life span are associated with oxidative stress resistance and upregulation of the gene expression of antioxidant enzymes. First, mutations in age-1 gene (PI3 kinase homologue) that confer life span extension, display oxidative stress resistance and increase in the gene expression of sod-3, one of two Mn-superoxide dismutases (SOD) and ctl-1, cytosolic catalase. In this study, these traits appear to be regulated by the following genetic pathway: daf-2 (insulin receptor family)-> daf-18 (PTEN homologue)-> age-1-> daf-16 (Fork head transcription factor family), similar to the genetic pathway for the life span extension. Second, we show that short-term exposure to hyperoxia extends life span slightly but significantly. This treatment increases oxidative stress resistance and the gene expression of three types of SOD isoforms. These results suggest that both of these two life span extensions are closely related with increase in the antioxidant defense function.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"24 4","pages":"179-86"},"PeriodicalIF":0.0,"publicationDate":"2001-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-001-0019-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31466776","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":"Metabolic alterations in genetically selected Drosophila strains with different longevities.","authors":"S A Buck, R Arking","doi":"10.1007/s11357-001-0016-2","DOIUrl":"10.1007/s11357-001-0016-2","url":null,"abstract":"<p><p>Sometime ago we obtained biomarker data suggesting that the earliest determining event in the expression of the extended longevity phenotype in our selected strains of Drosophila took place early in adult life at about 5-7 days of age. In a later series of experiments we documented that our La and Lb long lived strains underwent a specific up-regulation of the antioxidant defense system (ADS) genes and enzymes. This led to a reduction in oxidative damage and an extended longevity. In the current work, we assayed the activity of 17 metabolically important enzymes in 5-7 day old flies of 13 strains variously selected for different longevities. We conclude that the two sets of replicated long-lived strains have an altered metabolic pattern (relative to normal-lived animals) which is consistent with an increased flux through the pentose shunt and an enhanced NADP+ reducing system to support the increased activity of the ADS enzymes. This result can be interpreted as a shift of energy expenditure from reproduction to somatic maintenance. We conclude that theories based on differential energy allocations appear to empirically explain, at least in part, the mechanisms underlying the transformation of a normal longevity phenotype to an extended longevity phenotype.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"24 4","pages":"151-61"},"PeriodicalIF":0.0,"publicationDate":"2001-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3455292/pdf/11357_2001_Article_16.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31466773","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":"Aging-like alterations of SDH activity in Purkinje cell mitochondria of adult vitamin-E deficient rats.","authors":"P Fattoretti,&nbsp;C Bertoni-Freddari,&nbsp;T Casoli,&nbsp;G Di Stefano,&nbsp;N Gracciotti","doi":"10.1007/s11357-001-0011-7","DOIUrl":"https://doi.org/10.1007/s11357-001-0011-7","url":null,"abstract":"<p><p>The ultrastructural features of perikaryal mitochondria positive to the copper ferrocyanide cytochemical reaction due to SDH activity were investigated in Purkinje cells of adult rats fed a vitamin E (α-tocopherol) deficient diet (AVED) for 11 months. The mitochondrial volume fraction (volume density: Vv), the number of organelles/μm(3) of tissue (numeric density: Nv) and their average volume (V) were estimated by computer-assisted morphometry. The data obtained were compared with our previous results on 3, 12 and 24 month-old normally fed rats. In a comparison with age-matched controls, AVED animals showed significant decreases of the three morphometric parameters taken into account. These reductions were also observed in old, normally fed rats vs. the young and adult groups, but in AVED rats Vv and V decreased to a higher extent. In adult control animals, the percent of larger organelles (0.32 μm(3) >) decreases to less than 1%. Vitamin E deficiency resulted in a steeper reduction of this fraction of organelles, i.e. only 0.5% in the 0.24-0.32 μm(3) size range accounted for the largest mitochondria in the AVED group. Taken together, these data document a significant impairment of mitochondrial efficiency in old and AVED rats. We interpret these findings to support that the underlying processes of aging and vitamin E deficiency may share common mechanisms. Considering the antioxidant action of α-tocopherol and the SDH role in cellular bioenergetics, inadequate protection from free radical attacks appears to represent an important determinant in the age-related decline of the mitochondrial metabolic competence.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"24 3","pages":"79-84"},"PeriodicalIF":0.0,"publicationDate":"2001-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-001-0011-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31466771","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":"Mitochondrial oxidant generation and oxidative damage in Ames dwarf and GH transgenic mice.","authors":"H Brown-Borg, W T Johnson, S Rakoczy, M Romanick","doi":"10.1007/s11357-001-0012-6","DOIUrl":"10.1007/s11357-001-0012-6","url":null,"abstract":"<p><p>Aging is associated with an accumulation of oxidative damage to proteins, lipids and DNA. Cellular mechanisms designed to prevent oxidative damage decline with aging and in diseases associated with aging. A long-lived mouse, the Ames dwarf, exhibits growth hormone deficiency and heightened antioxidative defenses. In contrast, animals that over express GH have suppressed antioxidative capacity and live half as long as wild type mice. In this study, we examined the generation of H2O2 from liver mitochondria of Ames dwarf and wild type mice and determined the level of oxidative damage to proteins, lipids and DNA in various tissues of these animals. Dwarf liver mitochondria (24 months) produced less H2O2 than normal liver in the presence of succinate (p<0.03) and ADP (p<0.003). Levels of oxidative DNA damage (8ÕHdG) were variable and dependent on tissue and age in dwarf and normal mice. Forty-seven percent fewer protein carbonyls were detected in 24-month old dwarf liver tissue compared to controls (p<0.04). Forty percent more (p<0.04) protein carbonyls were detected in liver tissue (3-month old) of GH transgenic mice compared to wild types while 12 month old brain tissue had 53% more protein carbonyls compared to controls (p<0.005). Levels of liver malonaldehyde (lipid peroxidation) were not different at 3 and 12 months of age but were greater in Ames dwarf mice at 24 months compared to normal mice. Previous studies indicate a strong negative correlation between plasma GH levels and antioxidative defense. Taken together, these studies show that altered GH-signaling may contribute to differences in the generation of reactive oxygen species, the ability to counter oxidative stress and life span.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"24 3","pages":"85-96"},"PeriodicalIF":0.0,"publicationDate":"2001-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3455482/pdf/11357_2001_Article_12.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31466772","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":"Evidence of oxidative injury during aging of the liver in a mouse model.","authors":"A Colantoni,&nbsp;R Idilman,&nbsp;N de Maria,&nbsp;L A Duffner,&nbsp;D H Van Thiel,&nbsp;P L Witte,&nbsp;E J Kovacs","doi":"10.1007/s11357-001-0007-3","DOIUrl":"https://doi.org/10.1007/s11357-001-0007-3","url":null,"abstract":"<p><p>The aim of the present study was to determine whether oxidative stress contributes to aging of the liver in a mouse model. Liver was obtained from young (3-5 months old) and aged (18-24 months old) mice. No age-induced gross changes in liver morphology were detected by light microscopy. Apoptosis was measured using the fragment end labeling of DNA for the immunohistochemical identification of the apoptotic nuclei. The total apoptotic cells represented 1% of the total cells in livers of young mice and 8% in those of aged mice. Among the total apoptotic cells in livers of aged animals, 15% were hepatocytes, 40% sinusoidal endothelial cells, and 45% bile duct cells. Hepatic lipid peroxidation, expressed as malonaldehyde levels, protein oxidation, measured by protein carbonyl content, and DNA oxidation, measured as 8-hydroxy-2'-deoxyguanosine (oxo(8)dG), were significantly increased in the livers of aged animals as compared to younger mice. The apoptotic cells presented elevated levels of oxidized DNA, detected by immunohistochemistry using an antibody directed against oxo(8)dG in serial sections. These results suggest that livers of aged animals presents evidence of increased oxidative injury and apoptosis. Because the apoptotic cells in the aged livers are mostly bile duct cells and sinusoidal endothelial cells, the cells most sensitive to oxidative stress injury, it can be hypothesized that reactive oxygen species-induced apoptosis in these cells contributes to the aging of the liver.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"24 2","pages":"51-7"},"PeriodicalIF":0.0,"publicationDate":"2001-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-001-0007-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31466279","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":"TCR Vβ repertoire in an Italian longeval population including centenarians.","authors":"G Pennesi,&nbsp;M Morellini,&nbsp;P Lulli,&nbsp;S Cappellacci,&nbsp;G Brioli,&nbsp;C Franceschi,&nbsp;S Trabace","doi":"10.1007/s11357-001-0009-1","DOIUrl":"https://doi.org/10.1007/s11357-001-0009-1","url":null,"abstract":"<p><p>During the last years, the hypothesis that aging and diseases are two distinct phenomena, and that successful aging is possible for most humans, has been put forward. We studied the TCR Vβ repertoire of T lymphocytes of healthy longevals and centenarians as crossing point of genetic predisposition and environmental effects to longevity, using the Spectra-typing method. TCR Vβ1, Vβ8, and Vβ20 were found to be expanded in the longeval population, compared with the younger control population. This repertoire can have been shaped by the selective action of particular HLA alleles, or by the clonal expansion of specific T cell clones, able to modulate the immune response to endogenous and exogenous antigens. Moreover, the skewed Vβ usage and the clonal expansion seem to be the effects of physiological changes occurring with aging and not pathological signs of malignity.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"24 2","pages":"63-70"},"PeriodicalIF":0.0,"publicationDate":"2001-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-001-0009-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31466281","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}