Journal of the American Aging Association最新文献

{"title":"Retrospective analysis of the effects of low-dose, high frequency human growth hormone on serum lipids and prostate specific antigen.","authors":"E Chein,&nbsp;M J Gonzalez,&nbsp;N H Riordan","doi":"10.1007/s11357-001-0008-2","DOIUrl":"https://doi.org/10.1007/s11357-001-0008-2","url":null,"abstract":"<p><p>Background. Elevated serum total cholesterol (TC) and triglycerides (TG) are risk factors for atherosclerosis and ischemic heart disease. Adult growth hormone deficiency (AGHD) is associated with elevated TC and TG. Many treatment protocols for AGHD use relatively high doses of growth hormone (GH) given at low frequency, which is associated with increased incidences of edema, joint pains, and carpal tunnel syndrome. We have treated > 2200 patients using a low-dose high frequency (LDHF) dosing regimen of GH which results in similar beneficial subjective responses, and fewer of the side-effects associated with the higher-dosage treatment at a substantial cost savings. Clinically, in addition to increased insulin-like growth factor I (IGF-I), we observed lower TG and TC levels and no elevation of prostate specific antigen levels in treated patients. Methods. A retrospective analysis of IGF-I, TG, TC, and PSA data from our patient population was performed to test our hypothesis that positive objective responses of IGF-I, TG, and TC occur and that elevation of PSA does not occur in response to LDHF dosing regimen of GH. The mean duration of treatment of the analyzed data ranged from 181 to 259 days. Results. The mean plasma IGF-I level rose significantly (p<.00001) to a level 37% greater than baseline with treatment. TC and TG decreased significantly (p<.001) in those patients with elevated baseline values, and did not change significantly in those with normal baseline values. PSA concentrations decreased non-significantly during treatment, and few cases of edema, joint pain, or carpal tunnel were reported. Conclusions. Treatment of AGHD using the LDHF dosing regimen of GH resulted in significant increases in IGF-I, significant reductions in TC and TG levels in patients with elevated baseline values, no increase in PSA concentrations, and fewer side effects than other dosing regimens.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"24 2","pages":"59-62"},"PeriodicalIF":0.0,"publicationDate":"2001-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-001-0008-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31466280","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":"Effect of aging on mitochondrial and nuclear DNA oxidative damage in the heart and brain throughout the life-span of the rat.","authors":"A Herrero,&nbsp;G Barja","doi":"10.1007/s11357-001-0006-4","DOIUrl":"https://doi.org/10.1007/s11357-001-0006-4","url":null,"abstract":"<p><p>The oxygen radical-induced DNA lesion 8-oxo,7,8-dihydro-2'-deoxyguanosine (8-oxodG) is the most commonly measured marker of oxidative DNA damage, which is currently considered a main cause of aging. However, a detailed study of the age-related variations of this marker in both mitochondrial (mtDNA) and nuclear (nDNA) DNA of post-mitotic organs throughout the life span has not been previously performed. In this investigation 8-oxodG steady-state levels were simultaneously measured in mtDNA and nDNA in the heart and brain of Sprague-Dawley rats at up to five different ages covering most of the adult life span, 4, 8, 12, 17 and 24 months of age, using exactly the same digestion of DNA to deoxynucleosides and chromatographic procedures for mtDNA and nDNA. 8-oxodG levels were maintained without changes during young and middle age in all cases, but showed statistically significant increases at the older ages studied in the majority of the kinds of DNA investigated. These age-related increases in oxidative damage occurred in brain nDNA at 17 and 24 months of age, in heart nDNA at 24 months of age, and in brain mtDNA at 24 months of age, whereas no significant age-related changes were detected in heart mtDNA. Besides, 8-oxodG levels were various fold higher in mtDNA than in nDNA, both in brain and heart, at all the ages studied. The results show that oxidative damage to DNA is higher in the mtDNA than in the nDNA of post-mitotic tissues throughout the whole life span of the rat and that and increase in mtDNA and nDNA oxidative stress occurs in most cases in old animals.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"24 2","pages":"45-50"},"PeriodicalIF":0.0,"publicationDate":"2001-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-001-0006-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31466278","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":"30th Annual meeting of the American Aging Association, 15th annual meeting of the American College of Clinical Gerontology, 14th annual grantee conference of the American Federation for Aging Research","authors":"K. Smith, D. Perl, P. Hof","doi":"10.1007/s11357-001-0013-5","DOIUrl":"https://doi.org/10.1007/s11357-001-0013-5","url":null,"abstract":"","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"24 1","pages":"97-137"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-001-0013-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52978561","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":"Expression and regulation of apolipoprotein E receptors in the cells of the central nervous system in culture: A review.","authors":"Q W Fan,&nbsp;I Iosbe,&nbsp;H Asou,&nbsp;K Yanagisawa,&nbsp;M Michikawa","doi":"10.1007/s11357-001-0001-9","DOIUrl":"https://doi.org/10.1007/s11357-001-0001-9","url":null,"abstract":"<p><p>The importance of apolipoprotein E (apoE) in the central nervous system (CNS) became increasingly clear since the descovery that apoE ε4 allele is a major risk factor for Alzheimer's disease. ApoE is one of the major apolipoproteins that acts as a ligand for the cellular uptake of lipoproteins via apoE receptors, members of low-density lipoprotein receptor (LDLR) family, in the CNS. Recently, LDLR family has been shown to have new functions that modulate intracellular signalling and affect neuronal and glial functions, survival and regeneration. However, the pattern of expression of apoE receptors in the CNS has not been fully clarified yet. The LDLR, very low density lipoprotein receptor (VLDLR), LDLR-related protein (LRP), and apolipoprotein E receptor 2 (apoER2) are known to bind to and internalize apoE-containing lipoproteins. Here we summarize the expression of apoE receptors in the CNS and demonstrate additional our original data on cell type specific expression and regulation of those receptors in the CNS, using in situ hybridization and RT-PCR. The cells used in our study were highly enriched cultures of neurons, astrocytes, microglia and oligodendrocytes isolated from rat brain and neuroblastoma cell line, Neuro2a. All of these four types of receptors were shown to be expressed in neurons, astrocytes, microglia and oligodendrocytes, while LDLR and LRP were expressed in Neuro2a cells. We further examined the regulation of the expression of these receptors by altering the cholesterol content of the cells, and found that only the LDLR expression was downregulated following internalization of lipoprotein cholesterol and upregulated by cholesterol deprivation, in neuronal and astroglial cells. These data together with previous studies suggest that LDLR, VLDL, LRP, and apoER2 may be involved in apoE-mediated lipid uptake and/or intracellualr signalling in the cells of the CNS cells, i.e., neurons, astrocytes, microglia, and oligodendrocytes.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"24 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-001-0001-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31466274","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":"Peroxynitrite induces neuronal cell death in aging and age-associated disorders: A review.","authors":"W Maruyama,&nbsp;Y Kato,&nbsp;T Yamamoto,&nbsp;K Oh-Hashi,&nbsp;Y Hashizume,&nbsp;M Naoi","doi":"10.1007/s11357-001-0002-8","DOIUrl":"https://doi.org/10.1007/s11357-001-0002-8","url":null,"abstract":"<p><p>Peroxynitrite produced from nitric oxide and superoxide has been proposed to cause neuronal dysfunction and cell death in aging and age-related degenerative diseases. 3-Nitrotyosine, an oxidation product of tyrosine by peroxynitrite, was reported to increase in degenerating brains. In this paper, involvement of peroxynitrite in neuronal cell death was studied by analyses of human brains and in vitro experiments on cell death induced by a peroxynitrite-generating agent, SIN-1. 3-Nitrotyrosine-containing proteins were detected in lipofuscin, a typical aging-related pigment in human brains. The cytotoxicity of peroxynitrite was examined in human dopaminergic SH-SY5Y cells by use of SIN-1. SIN-1 induced apoptotic cell death in the cells, and increased the level of 3-nitrotyrosine-containing proteins. The intracellular transduction of death signal was studied in apoptosis induced by peroxynitrite. Apoptosis was induced by sequential death cascade, collapse of mitochondrial membrane potential, activation of caspases and fragmentation of nuclear DNA. In addition, phosphorylation of p38 mitogen activated phosphokinase (MAPK) was found to be associated with apoptosis by SIN-1, as shown by inhibition of apoptotic process by SB202190, a p38 inhibitor. Involvement of peroxynitrite in the cell death is discussed in relation to neuronal degeneration in aging and age-associated diseases.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"24 1","pages":"11-8"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-001-0002-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31466275","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 suggesting a nitric oxide-scavenging activity for traditional crude drugs, and action mechanisms of Sanguisorbae Radix against oxidative stress and aging.","authors":"T Yokozawa,&nbsp;C P Chen","doi":"10.1007/s11357-001-0003-7","DOIUrl":"https://doi.org/10.1007/s11357-001-0003-7","url":null,"abstract":"<p><p>In this series of experiments, we found that Sanguisorbae Radix extract possesses strong free radical-scavenging activity in vitro and in vivo. This crude drug protected against renal disease, which is closely associated with excessive generation of reactive oxygen species. We also showed that Sanguisorbae Radix extract can suppress lipid peroxidation and stimulate an antioxidant defense ability in SAM, suggesting that this crude drug may be an effective agent for ameliorating the pathological conditions related to excessive generation of free radicals and oxidant damage, particularly in the aging process.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"24 1","pages":"19-30"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-001-0003-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31466276","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":"Age-related neuronal vulnerability to brain ischemia: A potential target of gene therapy.","authors":"H Ooboshi, S Ibayashi, H Yao, J Takada, D D Heistad, M Fujishima","doi":"10.1007/s11357-001-0004-6","DOIUrl":"10.1007/s11357-001-0004-6","url":null,"abstract":"<p><p>Brain infarction is one of the most important age-associated diseases. We have developed aged animal models for brain ischemia, and found the age-related neuronal vulnerability to brain ischemia. Investigation of that mechanism would lead to the effective treatment of brain infarction in the elder population. Recent advancement of gene transfer technique has provided strong tools for the neuronal and vascular biology. We described our recent approaches of gene transfer to blood vessels, including cerebral circulation, using adenoviral vectors. Cerebral blood vessels, atherosclerotic endothelium, and ischemic brain tissue are good targets of gene transfer. Development of these techniques would offer new therapeutic strategies for the age-related neuronal vulnerability and other age-associated diseases.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"24 1","pages":"31-5"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3455646/pdf/11357_2001_Article_4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31466277","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":"Mitochondria, oxidative DNA damage, and aging.","authors":"R M Anson,&nbsp;V A Bohr","doi":"10.1007/s11357-000-0020-y","DOIUrl":"https://doi.org/10.1007/s11357-000-0020-y","url":null,"abstract":"<p><p>Protection from reactive oxygen species (ROS) and from mitochondrial oxidative damage is well known to be necessary to longevity. The relevance of mitochondrial DNA (mtDNA) to aging is suggested by the fact that the two most commonly measured forms of mtDNA damage, deletions and the oxidatively induced lesion 8-oxo-dG, increase with age. The rate of increase is species-specific and correlates with maximum lifespan. It is less clear that failure or inadequacies in the protection from reactive oxygen species (ROS) and from mitochondrial oxidative damage are sufficient to explain senescence. DNA containing 8-oxo-dG is repaired by mitochondria, and the high ratio of mitochondrial to nuclear levels of 8-oxo-dG previously reported are now suspected to be due to methodological difficulties. Furthermore, MnSOD -/+ mice incur higher than wild type levels of oxidative damage, but do not display an aging phenotype. Together, these findings suggest that oxidative damage to mitochondria is lower than previously thought, and that higher levels can be tolerated without physiological consequence. A great deal of work remains before it will be known whether mitochondrial oxidative damage is a \"clock\" which controls the rate of aging. The increased level of 8-oxo-dG seen with age in isolated mitochondria needs explanation. It could be that a subset of cells lose the ability to protect or repair mitochondria, resulting in their incurring disproportionate levels of damage. Such an uneven distribution could exceed the reserve capacity of these cells and have serious physiological consequences. Measurements of damage need to focus more on distribution, both within tissues and within cells. In addition, study must be given to the incidence and repair of other DNA lesions, and to the possibility that repair varies from species to species, tissue to tissue, and young to old.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"23 4","pages":"199-218"},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-000-0020-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31374962","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":"Mitochondria by Immo E. Scheffler","authors":"A. D. Grey","doi":"10.1007/s11357-000-0023-8","DOIUrl":"https://doi.org/10.1007/s11357-000-0023-8","url":null,"abstract":"","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"23 1","pages":"255-256"},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-000-0023-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52978476","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":"Growth hormone and aging.","authors":"A Bartke,&nbsp;H Brown-Borg,&nbsp;B Kinney,&nbsp;J Mattison,&nbsp;C Wright,&nbsp;S Hauck,&nbsp;K Coschigano,&nbsp;J Kopchick","doi":"10.1007/s11357-000-0021-x","DOIUrl":"https://doi.org/10.1007/s11357-000-0021-x","url":null,"abstract":"<p><p>The potential usefulness of growth hormone (GH) as an anti-aging therapy is of considerable current interest. Secretion of GH normally declines during aging and administration of GH can reverse age-related changes in body composition. However, mutant dwarf mice with congenital GH deficiency and GH resistant GH-R-KO mice live much longer than their normal siblings, while a pathological elevation of GH levels reduces life expectancy in both mice and men. We propose that the actions of GH on growth, development, and adult body size may serve as important determinants of aging and life span, while the age-related decline in GH levels contributes to some of the symptoms of aging.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"23 4","pages":"219-25"},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-000-0021-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31374963","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}