Journal of the American Aging Association最新文献

{"title":"The nature and mechanism of superoxide production by the electron transport chain: Its relevance to aging.","authors":"F Muller","doi":"10.1007/s11357-000-0022-9","DOIUrl":"https://doi.org/10.1007/s11357-000-0022-9","url":null,"abstract":"<p><p>Most biogerontologists agree that oxygen (and nitrogen) free radicals play a major role in the process of aging. The evidence strongly suggests that the electron transport chain, located in the inner mitochondrial membrane, is the major source of reactive oxygen species in animal cells. It has been reported that there exists an inverse correlation between the rate of superoxide/hydrogen peroxide production by mitochondria and the maximum longevity of mammalian species. However, no correlation or most frequently an inverse correlation exists between the amount of antioxidant enzymes and maximum longevity. Although overexpression of the antioxidant enzymes SOD1 and CAT (as well as SOD1 alone) have been successful at extending maximum lifespan in Drosophila, this has not been the case in mice. Several labs have overexpressed SOD1 and failed to see a positive effect on longevity. An explanation for this failure is that there is some level of superoxide damage that is not preventable by SOD, such as that initiated by the hydroperoxyl radical inside the lipid bilayer, and that accumulation of this damage is responsible for aging. I therefore suggest an alternative approach to testing the free radical theory of aging in mammals. Instead of trying to increase the amount of antioxidant enzymes, I suggest using molecular biology/transgenics to decrease the rate of superoxide production, which in the context of the free radical theory of aging would be expected to increase longevity. This paper aims to summarize what is known about the nature and mechanisms of superoxide production and what genes are involved in controlling the rate of superoxide production.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"23 4","pages":"227-53"},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-000-0022-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31374965","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":"Significance of hepatic xanthine oxidase and uric acid in aged and dietary restricted rats.","authors":"H Y Chung,&nbsp;B P Yu","doi":"10.1007/s11357-000-0013-x","DOIUrl":"https://doi.org/10.1007/s11357-000-0013-x","url":null,"abstract":"<p><p>Xanthine oxidase (XOD), one of the major intracellular sources of superoxide production, is well characterized as a causative factor in ischemia/reperfusion related damage. In the present study, we investigated age-effect on the status of XOD, an enzyme interconvertible with xanthine dehydrogenase (XDH) under oxidative stress. We also examined the modulation of the enzyme using the anti-oxidative action of dietary restriction (DR). We obtained evidence showing XOD activity to be significantly increased by DR, peaking at 24 months, although no progressive, age-related changes were noticed. On the other hand, while XDH activity decreased in ad libitum fed rats with age, DR maintained higher activity levels at 18 and 24 months of age. During aging, the conversion of XDH to XOD was slightly increased, as indicated by the XOD/XDH ratio. One novel finding of the present study is DR's ability to elevate the uric acid level, which likely augments the anti-oxidative defense system, thereby buffering against oxidatively stressed conditions during aging. Based on what is known about the antioxidative abilities of DR and uric acid, we propose that the high uric acid levels we observed in DR rats may well serve as part of a defense strategy to protect redox balance.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"23 3","pages":"123-8"},"PeriodicalIF":0.0,"publicationDate":"2000-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-000-0013-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31375111","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":"Gompertz - A program for evaluation and comparison of survival curves.","authors":"P Klemera, S Doubal","doi":"10.1007/s11357-000-0014-9","DOIUrl":"10.1007/s11357-000-0014-9","url":null,"abstract":"<p><p>Principles, properties and use of a program for evaluation of survival curves are described. Parameters of Gompertzian mortality curves are computed from survival data of two populations by help of nonlinear regression. The differences in parameters of both curves are evaluated statistically. This method evaluates effectively even survival data of very small populations. The results are presented in numeric, verbal and graphic forms. Finally, reading of the results is offered to distinguish changes corresponding to altered aging rate from changes caused by influences not affecting the basic mechanism of aging. Program GOMPERTZ in the form of Microsoft Excel workbook equipped with Visual Basic procedures is offered free through e-mail (klemera@faf.cuni.cz).</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"23 3","pages":"129-32"},"PeriodicalIF":0.0,"publicationDate":"2000-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3455601/pdf/11357_2000_Article_14.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31373426","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":"Alzheimer's disease: A hypothesis on pathogenesis.","authors":"D Harman","doi":"10.1007/s11357-000-0017-6","DOIUrl":"10.1007/s11357-000-0017-6","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the major cause of dementia. It is a systemic disorder whose major manifestations are in the brain. AD cases can be categorized into two groups on the basis of the age of onset-before or after about age 60. The majority of cases, 90-95 percent, are in the late onset category. Early onset cases are largely, if not all, familial (FAD). These are caused by mutations in the genes for the amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2). In contrast late onset cases are mainly sporadic. The disorder is characterized by intraneuronal fibrillary tangles, plaques, and cell loss. The brain lesions in both early and late-onset AD are the same, and in the same distribution pattern, as those seen in individuals with Down's syndrome (DS) and in smaller numbers in normal older individuals. Extensive studies of AD have yet to result in a generally accepted hypothesis on the pathogenesis of the disorder. Major emphasis has been placed on the role of amyloid, the neurotoxin formed by the action of free radicals on preamyloid. The observation that AD lesions are frequently present in normal older individuals prompted the hypothesis that AD is the result of faster than normal aging of the neurons associated with it. This hypothesis provides plausible explanations for FAD and AD. FAD is associated with mutations in APP, PS1, and PS2. These substances, along with their normal counterparts, undergo proteolytic processing in the endoplasmic reticulum (ER). The mutated compounds, aside from increasing the ratio of βA42 to βA40, may down-regulate the calcium buffering activity of the ER in a manner akin to one or more of the many compounds known to do so. Decreases in the ER calcium pool would cause compensatory increases in other calcium pools, particularly in mitochondria. Increases in mitochondrial calcium levels are associated with enhanced formation of superoxide radical formation, and hence of the rate of aging. SAD may be caused by nuclear and/or mitochondrial DNA mutations beginning early in life that enhance mitochondrial superoxide radical formation in the neurons associated with the disorder. The above explanations for FAD and AD are suggestive of measures to prevent and for treatment.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"23 3","pages":"147-61"},"PeriodicalIF":0.0,"publicationDate":"2000-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3455602/pdf/11357_2000_Article_17.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31373912","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":"Insulin receptors in mouse brain: Reversibility of age-related impairments by a thymic extract.","authors":"A Zaia,&nbsp;L Piantanelli","doi":"10.1007/s11357-000-0015-8","DOIUrl":"https://doi.org/10.1007/s11357-000-0015-8","url":null,"abstract":"<p><p>Recently, we have shown that insulin receptors (InsRs) in the brain undergo impairments with aging. Interestingly, age-related alterations of brain InsRs, are not irreparable as thymus grafts are able to recover them. With the present study we verified the possibility that an aqueous extract from calf thymus (TME) can mimic the restoring action of age-related impairments induced by thymus graft. InsR characteristics were assayed in a group of 25 months old BALB/c-nu mice treated with TME: 2μg/g body weight every third day, for total five subcutaneous injections. The last dose was injected the day before animals were killed. Other two groups of young (4 months) and old (25 months) mice received saline solution with the same schedule. A two-sites model analysis of receptor data confirms the age-dependent decrease of InsR number and kd previously observed in the high affinity population. Furthermore, a statistically significant recovery of number impairment is shown in TME-treated animals. On the contrary, the characteristics of the low affinity receptor subset show no statistically significant differences among the three animal models studied. TME induced recovery of the age-related changes found in brain InsRs, together with previously observed regulatory action of the same thymic extract on the adrenergic system, suggest that thymic gland does not necessarily have to mutually interact with other controlling systems for maintaining or recoving homeostasis of the complex neuroendocrine network during development and aging.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"23 3","pages":"133-9"},"PeriodicalIF":0.0,"publicationDate":"2000-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-000-0015-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31373910","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":"Diet restriction and age alters skeletal muscle capillarity in B6C3F1 mice.","authors":"N Keith, R T Bronson, R D Lipman, W Ding, L Lamont, A C Cosmas, T G Manfredi","doi":"10.1007/s11357-000-0016-7","DOIUrl":"10.1007/s11357-000-0016-7","url":null,"abstract":"<p><p>The effects of 40% diet restriction on skeletal muscle fiber area, capillary density (CD) and capillary to fiber ratio (C/F) were compared in 12, 24 and 30-month-old female B6C3F1 female hybrid mice. We hypothesized that diet restriction (DR) would retard the aging effects observed in skeletal muscle, in particular DR would pose opposite effects on skeletal muscle capillarity and fiber area. Samples were prepared for light microscopic examination by standard methods and for morphometric analysis using NIH-image software. There was a significant effect of age on muscle fiber area (p<0.05). The age-associated decrease in fiber area between 12 and 30 months of age was greater (p<0.05) in the ad libitum (AL) (37.7%) animals as compared to the diet restricted (DR) mice (29.2%). Diet had a significant effect on CD (p<0.05) and C/F (p<0.05). This finding suggests that the lower capillarity in the older DR mice may have been due to their larger muscle fibers. The results of this study support the contention that diet restriction delays the progression of age-associated muscle atrophy.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"23 3","pages":"141-5"},"PeriodicalIF":0.0,"publicationDate":"2000-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3455604/pdf/11357_2000_Article_16.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31373911","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 role of metabolism in aging.","authors":"L S Luckinbill, P Foley","doi":"10.1007/s11357-000-0009-6","DOIUrl":"10.1007/s11357-000-0009-6","url":null,"abstract":"<p><p>Metabolism appears to play a significant role in determining the rate of aging. Long-lived mutants and selected stocks of model experimental organisms exhibit characteristic changes in life history and physiological features consistent with altered metabolism. Specifically, these include the accumulation of metabolite pools of glycogen, lipid and polyhedric alcohols, suggesting that prolonged life is associated with restriction of the flow of carbon through glycolysis. Limiting carbon flow by reducing caloric intake is well known to extend life. Studies examining the mRNA expression pattern of functional gene groups generally indicate that nutrient restriction does affect metabolism. One study of Drosophila melanogaster has demonstrated that the flux of carbon through glycolysis is reduced in larvae of selected long-lived populations. Here we propose a new hypothesis describing the interaction between the glycation process, glucose level, damage by free oxygen radicals and chaperonin proteins. Intermediate steps of the Maillard Reaction produce free radicals, similar to those produced during respiration, that also damage lipids, proteins and DNA. Antioxidant enzymes themselves can be inactivated by glycation. This establishes a positive feed-back between the rate of metabolism, glucose availability and damage by free oxygen radicals. The high levels of available glucose in ad libitum feeding should add to production of radicals, reduce levels of protective antioxidants and proportionally increase damage by free radicals. Thus, caloric restriction should lower available glucose, increase the level of antioxidants and thereby slow the rate of aging. Chaperonins act to block glycation, reducing its negative effect on antioxidant enzymes release and contribution of free radicals.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"23 2","pages":"85-93"},"PeriodicalIF":0.0,"publicationDate":"2000-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3455785/pdf/11357_2000_Article_9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31373510","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":"Endocrine and metabolic changes in human aging.","authors":"W A Banks,&nbsp;J E Morley","doi":"10.1007/s11357-000-0011-z","DOIUrl":"https://doi.org/10.1007/s11357-000-0011-z","url":null,"abstract":"<p><p>Numerous alterations in hormonal secretion occur with aging. In general, these tend towards a disintegration of the normal cyclic secretory patterns resulting in lower total circulating levels. In addition, declines in receptors and postreceptor function further decreases the ability of the hormonal orchestra to maintain coordinated function throughout the organism. Clues to some of these age-related changes in humans may come from the study of simpler organisms where regulatory systems are known to modulate the aging process. In particular, the interactions among the environment, hormones, and insulin receptor genes have led to new insights into the genetic control of longevity and the development of syndrome X.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"23 2","pages":"103-15"},"PeriodicalIF":0.0,"publicationDate":"2000-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-000-0011-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31375104","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":"Ammonia, respiration, and longevity in nematodes: insights on metabolic regulation of life span from temporal rescaling.","authors":"J J Thaden, R J Shmookler Reis","doi":"10.1007/s11357-000-0008-7","DOIUrl":"10.1007/s11357-000-0008-7","url":null,"abstract":"<p><p>To better understand metabolic correlates of longevity, we used a graphical technique to compare the adult temporal patterns of several markers of metabolic activity - ammonia elimination, oxygen consumption rate, ATP levels, and (in freeze-permeabilized worms) the rate of NADPH-activated, lucigenin-mediated superoxide formation - as observed by us and others in normal and long-lived mutant Caenorhabditis elegans strains. All of these traits declined with time, and when their logarithms were plotted against time, appeared reasonably linear for most of the duration of the experiments. The profiles for ammonia output conformed well to parallel regression lines; those for the other metabolic parameters varied widely in slope as originally plotted by the authors, but much less so when replotted as logarithms against adjusted time, scaled by the reciprocal of strain longevity. This is consistent with coregulation of life span, respiration rate, ATP levels, lucigenin reactivity, but not ammonia excretion, by a physiological clock distinguishable from chronologic time. Plots, scaled appropriately for equalized slopes, highlighted y-axis intercept differences among strains. On rescaled plots, these constitute deviations from the expectation based on 'strain-specific clock' differences alone. With one exception, y-intercept effects were observed only for mutants in an insulin-like signaling pathway.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"23 2","pages":"75-84"},"PeriodicalIF":0.0,"publicationDate":"2000-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3455786/pdf/11357_2000_Article_8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31373509","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":"Patterns of metabolic activity during aging of the wild type and longevity mutants of Caenorhabditis elegans.","authors":"B P Braeckman,&nbsp;K Houthoofd,&nbsp;J R Vanfleteren","doi":"10.1007/s11357-000-0007-8","DOIUrl":"https://doi.org/10.1007/s11357-000-0007-8","url":null,"abstract":"<p><p>At least three mechanisms determine life span in Caenorhabditis elegans. An insulin-like signaling pathway regulates dauer diapause, reproduction and longevity. Reduction-or loss-of-function mutations in this pathway can extend longevity substantially, suggesting that the wild-type alleles shorten life span. The mutations extend life span by activating components of a dauer longevity assurance program in adult life, resulting in altered metabolism and enhanced stress resistance. The Clock (Clk) genes regulate many temporal processes, including life span. Mutation in the Clk genes clk-1 and gro-1 mildly affect energy production, but repress energy consumption dramatically, thereby reducing the rate of anabolic metabolism and lengthening life span. Dietary restriction, either imposed by mutation or by the culture medium increases longevity and uncovers a third mechanism of life span determination. Dietary restriction likely elicits the longevity assurance program. There is still uncertainty as to whether these pathways converge on daf-16 to activate downstream longevity effector genes such as ctl-1 and sod-3. There is overwhelming evidence that the interplay between reactive oxygen species (ROS) and the capacity to resist oxidative stress controls the aging process and longevity. It is as yet not clear whether metabolic homeostasis collapses with age as a direct result of ROS-derived damage or is selectively repressed by longevity-determining genes. The dramatic decline of protein turnover during senescence results in the accumulation of altered enzymes and in a gradual decline of metabolic performance eventually followed by fatal failure of the system.</p>","PeriodicalId":89818,"journal":{"name":"Journal of the American Aging Association","volume":"23 2","pages":"55-73"},"PeriodicalIF":0.0,"publicationDate":"2000-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11357-000-0007-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31373508","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}