Abstract：
:Overproduction of oxidants and free radicals in ageing tissues induces nitro-oxidative stress, which has recently been implicated in the pathogenesis of cardiovascular dysfunction associated with ageing. Peroxynitrite, a strong cytotoxic oxidant damages proteins and DNA and activates several pathways causing tissue injury, including the peroxynitrite-poly(ADP-ribose) polymerase (PARP) pathway. In this study, we investigated the effectiveness of the peroxynitrite decomposition catalyst FP15 on ageing-associated cardiac and vascular dysfunction. Young and ageing rats were treated with vehicle or FP15 intraperitoneally. Using a microtip Millar pressure catheter we performed left ventricular blood pressure analysis to assess systolic and diastolic function. Endothelium-dependent and -independent vasorelaxation of isolated aortic rings were investigated by using acetylcholine and sodium nitroprusside. Ageing animals showed a marked reduction of systolic and diastolic cardiac function and loss of endothelium-dependent relaxant responsiveness of aortic rings. FP15-treatment significantly improved cardiac performance and endothelial function. Immunohistochemical staining confirmed that FP15 effectively reduced nitrosative stress and prevented the activation of PARP in the aortic wall of ageing rats. Our results demonstrate the importance of endogenous peroxynitrite-overproduction in the pathogenesis of ageing-associated cardiovascular dysfunction. Pharmacological decomposition of peroxynitrite by FP15 may represent a novel therapeutic utility to improve cardiac and vascular dysfunction associated with ageing.
journal_name
Mech Ageing Devjournal_title
Mechanisms of ageing and developmentauthors
Radovits T,Seres L,Gero D,Lin LN,Beller CJ,Chen SH,Zotkina J,Berger I,Groves JT,Szabó C,Szabó Gdoi
10.1016/j.mad.2006.09.005subject
Has Abstractpub_date
2007-02-01 00:00:00pages
173-81issue
2eissn
0047-6374issn
1872-6216pii
S0047-6374(06)00214-4journal_volume
128pub_type
杂志文章abstract：:Normal diploid Syrian hamster dermal mesenchymal cell strains, regardless of the age of the tissue of origin, exhibit in vitro cellular senescence. The frequency of spontaneous escape from senescence and conversion to a permanent cell line is less than 5% among replicate flasks. The overall pattern of senescence of ce...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(86)90032-1
更新日期：1986-04-01 00:00:00
abstract：:Human cytomegalovirus (HCMV) establishes a highly prevalent life-long latent infection. Though generally subclinical, HCMV infection may have severe consequences during fetal development and in immunocompromised individuals. Based on epidemiological studies HCMV(+) serology has been associated with the development of ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/j.mad.2016.06.010
更新日期：2016-09-01 00:00:00
abstract：:During senescence, autofluorescent lysosomal storage bodies known as lipofusin or age pigment accumulate in many post-mitotic types of cells. Among these cell types is the retinal pigment epithelium (RPE) of the mammalian eye. The mechanisms of lipofuscin formation and accumulation have been studied more extensively i...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2004.11.004
更新日期：2005-04-01 00:00:00
abstract：:Arteriosclerosis is believed by many to represent the aging process of arteries and to be responsible for the cause-specific deaths at any age in industrialized countries. However, the increasing rate of (A) associated with steadily increasing life expectancy invited studies of the average age at death (AAD) of condit...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(91)90030-4
更新日期：1991-02-01 00:00:00
abstract：:Certain anatomic and functional parameters of the eye change with increasing chronological age. They may, therefore, serve as potential biomarkers of ageing. We investigated associations between four such ocular parameters (lens density, retinal vessel calibre, corneal endothelial cells and retinal nerve fibre layer t...
journal_title：Mechanisms of ageing and development
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1016/j.mad.2013.05.002
更新日期：2013-07-01 00:00:00
abstract：:The healing of normal incisional wounds and ischemic flap wounds was investigated in young (10 weeks) and old (102-104 weeks) rats, together with the effect of treatment with hyperbaric oxygen on day 0-3 of healing. After 10 days of healing all biomechanical strength parameters of normal wounds were decreased by 30-40...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(96)01782-4
更新日期：1996-10-25 00:00:00
abstract：:Ascorbic acid content decreased with age in livers of male rats but not in those of female rats. The influence of aging on the regeneration of ascorbic acid from dehydroascorbic acid was investigated as a possible cause of declining ascorbate concentrations. The results demonstrate that hepatic NADPH-dehydroascorbic a...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(96)01784-8
更新日期：1996-11-13 00:00:00
abstract：:In this study, we proposed a hypothesis that chromatin of mouse hepatocytes exhibits age-related reduction of fractal dimension. This hypothesis was based on previously published works demonstrating that complexity of biological systems such as tissues, decreases during the process of physiological aging. Liver tissue...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2016.07.002
更新日期：2016-07-01 00:00:00
abstract：:To investigate age-related changes in gene expression in WI-38 cells, we isolated RNA from young and senescent, quiescent cultures and made subtracted cDNA libraries. Density-arrested cells were incubated in serum-free MCDB-104 for 3 days. RNA was then isolated and subtracted cDNA libraries were made in the phagemid v...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(92)90039-g
更新日期：1992-09-01 00:00:00
abstract：:The effect of life-long diets containing different concentrations of selenium and vitamin E on the age pigment accumulation in the rat superior cervical ganglion, vagal ganglion and dorsal root ganglion, was studied using microspectrofluorometry. All types of ganglia showed unchanged amounts of age pigments at low or ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(90)90162-9
更新日期：1990-01-01 00:00:00
abstract：:Mortality trends in industrialized countries are characterized by declines in vascular disease (ischemic heart disease and stroke) and rises in cancers and degenerative diseases. These trends are typically analyzed by examining each disorder in isolation using the perspective of genetic and environmental influences. H...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(92)90037-e
更新日期：1992-09-01 00:00:00
abstract：:Cellular and organismal decline is, in part, believed to be a consequence of oxygen and nitrogen-based reactants which persistently damage macromolecules throughout a lifetime. The resulting accumulation of damaged molecules eventually seriously compromises essential functions of cells leading to their death. Excessiv...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/s0047-6374(01)00384-0
更新日期：2002-04-30 00:00:00
abstract：:Developments in medicine have led to a significant increase in the average human lifespan. This increase in aging is most readily apparent in the case of HIV where antiretroviral therapy has shifted infection from a terminal to a chronic but manageable disease. Despite this advance, patients suffer from co-morbidities...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2018.07.008
更新日期：2018-10-01 00:00:00
abstract：:The decline in phytohemagglutinin (PHA) responsiveness of spleen cells from aged mice was studied in an effort to determine the nature of the depressed PHA reactivity. The reduced response of DNA synthesis (thymidine incorporation) to PHA stimulation could not be attributed to a decreased viability of spleen lymphocyt...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(75)90005-6
更新日期：1975-01-01 00:00:00
abstract：:During adult life, the thymus involutes and thymic output of mature T cells drastically declines. The molecular events underlying this process are not well understood. Here, we present evidence of the importance of miRNAs in regulating T cell differentiation in the aged. miRNAs are a wide-ranging regulatory element in...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2010.09.008
更新日期：2010-11-01 00:00:00
abstract：:The present work explores the application of information theoretical measures, such as entropy and normalized mutual information, for research of biomarkers of aging. The use of information theory affords unique methodological advantages for the study of aging processes, as it allows evaluating non-linear relations be...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2017.01.003
更新日期：2017-04-01 00:00:00
abstract：:The efficient use of nutrients is important in development and aging. In this study, we asked if the protein repair methyltransferase has a related or additional role in energy metabolism and stress response in the nematode Caenorhabditis elegans. Worms lacking the pcm-1 gene encoding this enzyme exhibit reduced longe...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2008.09.019
更新日期：2008-12-01 00:00:00
abstract：:The responses of the left and right ventricles (LV and RV) to physical conditioning in cold (25 degrees C) and thermoneutral temperatures (35 degrees C), with special reference to lactate dehydrogenase (LDH) and its isoenzyme profile, were studied in the 2-month (young)- and 12-month (middle-aged)-old rats. Moderate h...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(99)00004-4
更新日期：1999-04-01 00:00:00
abstract：:Experimental studies have not shown that the 'common' clinical experience, which suggests that wound healing is impaired in an old organism, is valid for healthy old experimental animals. We have developed a model in the rat for ischemic wound healing by using an H-shaped double skin flap, where the test wound is the ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(91)90094-g
更新日期：1991-05-01 00:00:00
abstract：:Recent studies show that cellular and mitochondrial iron increases with age. Iron overload, especially in mitochondria, increases the availability of redox-active iron, which may be a causal factor in the extensive age-related biomolecular oxidative damage observed in aged organisms. Such damage is thought to play a m...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/j.mad.2010.04.007
更新日期：2010-07-01 00:00:00
abstract：:Evolution of longevity of the ungulates, carnivores and primates is reviewed. Special emphasis is focused on recent evolutionary history of longevity along the hominid ancestral-descendant sequence leading to modern man. Maximum life span potential (MLP) or the change in MLP is predicted in extinct species by (1) a ph...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/0047-6374(79)90110-6
更新日期：1979-02-01 00:00:00
abstract：:Several alternative mortality models fit Swedish old-age mortality data equally well. The models build on two different concepts of the heterogeneity of individuals in a population. The first concept concerns fixed, genetic differences among individuals in their risk of death. The second concept involves acquired susc...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(94)90094-9
更新日期：1994-05-01 00:00:00
abstract：:In this study, we showed that in flies kept for 2 weeks at 1 (terrestrial gravity), 3 or 5 x g (hypergravity, HG) before transfer to 1 x g, resistance to heat remained higher in HG flies for several weeks after the transfer. The measurement of heat shock protein 70 (hsp70) indicated no induction of the protein in HG, ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(99)00024-x
更新日期：1999-06-01 00:00:00
abstract：:The synthesis of sulfated proteoglycans in late fetal (19th to 22nd day of intrauterine life), early postnatal, and adult liver tissue as well as in hepatocytes and their distribution in plasma membranes were studied. Overall proteoglycan production is enhanced two-fold in fetal as compared with adult liver tissue. In...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(85)90097-1
更新日期：1985-09-01 00:00:00
abstract：:Restriction of food intake extends lifespan in evolutionarily diverse organisms, including mammals. Dietary restriction (DR) also delays the appearance of ageing-related damage and pathology and keeps organisms in a youthful state for longer. DR has hence been suggested to lower the rate of ageing. Analysis of mortali...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/j.mad.2004.09.017
更新日期：2005-01-01 00:00:00
abstract：:Replicative senescence in human diploid fibroblasts is characterised by an exhaustion of proliferative potential and permanent cell cycle arrest. During senescence, telomere shortening-generated DNA damage activates p53 pathway that upregulates cell cycle inhibitors, such as p21. Human p400 ATPase is a chromatin remod...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2012.11.001
更新日期：2012-11-01 00:00:00
abstract：:A 3'-->5' exonuclease found in rat liver excises mispaired nucleotides at the 3'-hydroxyl end of primer chains such as poly dA-d(T9-C). Consequently, the priming activity of the chain from which the mispaired base was cut is greatly increased during DNA synthesis. These results suggest that the 3'-->5' exonuclease act...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(98)00083-9
更新日期：1998-09-15 00:00:00
abstract：:The endothelin-1 (ET-1) concentrations were measured by RIA in the media of confluent monolayer cultures of rat articular chondrocyte (RAC) exposed to fetal calf serum (FCS) and several growth factors and cytokines. The cells were obtained from 1- and 18-month-old rats. First passage cells were starved in Dulbecco's m...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(99)00117-7
更新日期：2000-02-22 00:00:00
abstract：:Previous studies on DNA repair in ageing have demonstrated increased frequencies of single and double strand breaks in lymphocytes from elderly subjects and, as a consequence, decreased efficiency in DNA replication. We have investigated the relationship between cell proliferation and the nuclear expression of ku prot...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(97)00137-1
更新日期：1998-01-30 00:00:00
abstract：:Extrachromosomal circular DNA complexes from peripheral blood lymphocytes from inbred mice of accelerated senescence, were detected by mica-press-adsorption method. In senescence-resistant series (SAM-R), polydisperse circular DNAs were observed at 7 weeks of age and a restricted size class of small circular forms of ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(85)90051-x
更新日期：1985-01-01 00:00:00
