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PubMed1980

Effects of chromosome constitution on growth and longevity of human skin fibroblast cultures.

Employing standardized cell-culture methods, 10 euploid and 22 constitutionally aneuploid human skin fibroblast strains were assessed in triplicate for total growth potential, growth rates, population-doubling times, and cloning. In addition, longitudinal growth rate studies were carried out with otherwise isogenic 45,X and 47,XXX clonal cultures derived from a mosaic parental strain. Growth rates and longevities were cell-strain specific and highly reproducible among sister cultures of a given strain. There was no systematic correlation between chromosome constitution and any of the measured growth parameters. Trisomic as well as monosomic strains showed the same degree of variability with respect to these parameters as did euploid cultures. In particular, 4 trisomy 21 strains were not unusually short-lived, nor were clones with the 47,XXX constitution compared to those with 45,X karyotypes. We therefore conclude that the cumulative number of in vitro doublings preceding senescence of fibroblast-like cells cultured from skin does not differ significantly among cultures derived from humans who have a normal karyotype, trisomy 13, 18, or 21, the 45,X constitution, or various combinations of extra X and Y chromosomes.

Aneuploidy↗
PubMed2005

Cellular inheritance of a Cre-activated reporter gene to determine Paneth cell longevity in the murine small intestine.

Here, we exploit an absolute differential between stem and progeny cells in their ability to express Cre from a somatically inducible transgene to determine the longevity of intestinal Paneth cells. In the Ahcre transgenic line induction of Cre recombinase allows constitutive activation of a Cre-activated reporter in intestinal precursors but not in Paneth cells. The time taken for Paneth cells to inherit the reporter (EYFP) was measured in adult Ahcre/R26R-EYFP animals. Using confocal microscopy of TOPRO-3-stained sections, both precursors and Paneth cells were identified and subsequently scored for EYFP expression. It takes up to 57 days for Paneth cells to inherit the reporter, making them three times longer-lived than previously indicated using nucleotide incorporation and suggesting that such determinations of cell turnover may be significant underestimates.

Animals↗
PubMed1998

Determinants of the longevity of socially learned food preferences of Norway rats.

We conducted three experiments to examine variables that might influence the longevity of socially induced food preferences in Norway rats. The duration of social influence on the food choices of 42-day-old rats (1) increased with both increasing numbers of demonstrators and increasing numbers of demonstrations by a single demonstrator, (2) varied with the temporal distribution of demonstrations, but (3) did not vary with the age of demonstrators. The results suggest that a single episode of social learning produces short-term, but not long-term, effects on a Norway rat's food choices. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1999

Orthologues of the Caenorhabditis elegans longevity gene clk-1 in mouse and human.

The clk-1 gene was isolated from the long-lived mutant of Caenorhabditis elegans and was suggested to play a biological role in longevity (Ewbank et al., 1997, Science 275: 980-983). The primary structure of CLK-1 showed a significant homology to Saccharomyces cerevisiae Coq7p/Cat5p, which is required for the biosynthesis of ubiquinone and the derepression of gluconeogenic genes. In the present study, we isolated and characterized human and mouse orthologues of the COQ7/CLK-1 gene. Sequence analysis of both the human and the mouse COQ7 cDNAs showed an open reading frame composed of 217 amino acids with calculated molecular mass of 24,309 and 24,044 Da, respectively. Homology search revealed that human COQ7 showed 85% identity to mouse COQ7, 89% identity to rat COQ7, 53% identity to C. elegans CLK-1, and 37% identity to S. cerevisiae Coq7p/Cat5p. Zoo blot analysis implied that the COQ7 gene was well conserved among mammal, bird, and reptile genomes. Tissue blot analysis showed that human COQ7 is dominantly transcribed in heart and skeletal muscle. Genomic analyses revealed that the human COQ7 gene is composed of six exons spanning 11 kb of human genome as a single-copy gene. Radiation hybrid mapping assigned the COQ7 gene to human chromosome 16p12.3-p13.11.

Amino Acid Sequence↗
PubMed2001

Cloning, mapping, and characterization of a human homologue of the yeast longevity assurance gene LAG1.

We have identified LASS2, a previously unknown human homologue of the yeast longevity assurance gene LAG1. The LASS2 transcript is highly expressed in liver and kidney, which is very different from the expression of the previously identified human LAG1 homologue LAG1Hs-1. Radiation hybrid mapping studies indicated that LASS2 is located on chromosome 1q11. Yeast two-hybrid screening and glutathione S-transferase pull-down assays showed that the LASS2 protein interacts with several membrane-associated receptors or transporters. Furthermore, LASS2 protein was able to inhibit the colony formation of human hepatoma cells in vitro, which suggests that this gene may be involved in the regulation of cell growth.

Amino Acid Sequence↗
PubMed2002

Factors affecting the longevity of a short-term velocity store for predictive oculomotor tracking.

Fast (up to 30 degrees /s) anticipatory smooth pursuit eye movements can be built up with repeated transient motion stimuli. It is thought that such stimuli charge a putative internal store of velocity information that can then drive anticipatory movements in the absence of a target. The aim of this study was to investigate the longevity of this store. Previous experiments with single ramp stimuli (Wells and Barnes 1998) suggested that the store lasts for only a few seconds before decaying to a baseline level. In the current study we investigate the possibility that the store was not maximally charged by single stimuli, precipitating its decay. The magnitude of the anticipatory response was indexed by smooth eye velocity 100 ms after target onset ( V(100)). In experiment 1 the build-up of the anticipatory response was examined by presenting sets of stimuli (comprising from one to five ramps) within a tracking phase and leaving a dark period (the 'gap') of 9.6 s between successive tracking phases. Each ramp was preceded by an audio warning cue and was accompanied throughout its 480 ms duration by an audio tone. Audio cues continued during the gap to reinforce timing information. V(100) for the first and last ramps of each set increased as the number of ramps was increased from one to three but reached an asymptotic level thereafter, suggesting that the velocity store is maximally charged after three presentations. In experiment 2 the store was maximally charged by presenting five ramps in each tracking phase and its decay was examined by leaving gaps of either 7.2 s or 14.4 s between successive tracking phases. V(100) was not diminished after either gap interval. In experiment 3 the velocity store was less well consolidated during tracking phases comprising two ramps. V(100) for the first response after the gap was unaffected by the 7.2 s gap interval but was significantly reduced when the gap interval was 14.4 s. The interval between the warning cue and ramp onset strongly influenced the magnitude of the anticipatory response, the optimum level being elicited by a cue time of 600 ms. In conclusion, this study has shown that the internal velocity store can be sustained for periods as long as 14.4 s provided that it is initially charged to a sufficiently high level and that accurate external timing cues are provided. Furthermore, we provide evidence to suggest that this process may be controlled by a two-part sample and hold mechanism.

Acceleration↗
PubMed1998

Mitochondrial DNA rearrangements associated with mF plasmid integration and plasmodial longevity in Physarum polycephalum.

Plasmodial cultures of Physarum polycephalum have defined life spans and undergo a reproducible decline (senescence) before losing the ability to be subcultured. Studies of the mtDNA of a long-lived Physarum strain, which does not undergo senescence, revealed a 7. 9-kb insertion in its mtDNA. This insertion is derived from a mitochondrial plasmid which enhances mitochondrial fusion and mtDNA recombination. Four different recombination events are required to convert the parental mtDNA to the form found in the long-lived strain. An additional recombination event, which deletes a 2.4-kb region of the insert from the long-lived strain, has been identified in the mtDNA of a normally senescing strain. These observations imply a mitochondrial involvement in the process of plasmodial senescence and implicate a region of the DNA derived from the mitochondrial plasmid as being necessary for plasmodial longevity.

Animals↗
PubMed2006

Strong expression of a longevity-related protein, SIRT1, in Bowen's disease.

The class III histone deacetylase (HDAC), SIRT1, is a mammalian homologue of the Saccharomyces cerevisiae chromatin-silencing factor Sir2 that regulates longevity. SIRT1 regulates cell survival via deacetylation of p53 and forkhead transcription factors, and overexpression of SIRT1 is reported to be essential for cell growth and survival in some kinds of cancer. To elucidate the role of SIRT1 in human skin carcinogenesis, we have examined SIRT1 protein expression in 20 cases each of squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Bowen's disease (BD), and actinic keratosis (AK) by immunohistochemical analysis. Overexpression of SIRT1 is frequently observed in all kinds of non-melanoma skin cancers included in this study. In particular, strong expression was observed in all cases of BD. In addition, no obvious difference between AK and SCC was observed in the expression of SIRT1, suggesting that overexpression of SIRT1 may have some relevance to the early stage of skin carcinogenesis. We suppose that SIRT1 could be one of the critical targets for future therapy with the aim of inhibiting cell proliferation and promoting apoptosis in non-melanoma skin cancers.

Apoptosis↗
PubMed1997

Longevity of glass ceramic inlays and amalgam--results up to 6 years.

Ceramic inlays are discussed as one option for the substitution of amalgam restorations. The purpose of this study was to determine the longevity of glass ceramic inlays and amalgam restorations placed by the author: 123 class I and class II Dicor inlays placed with adhesive techniques and 163 amalgam class I and class II restorations were investigated. The observation time for the inlays varied from 4 to 82 months. The inlays were clinically investigated using modified USPHS criteria and documented photographically. Kaplan-Meier statistics were used to calculate the survival rate. From the 123 evaluated inlays 12 inlays (9.7%) failed: 7 due to fractures, 4 because of endodontic problems and 1 inlay was replaced due to persisting postoperative pain. All fractures could be explained by case selection errors. According to the Kaplan-Meier method, the estimated success rate after 6 years was 76% for the Dicor inlays and 87% for the amalgam restorations (control group). The difference was not statistically significant. It was concluded that Dicor inlays may be used as a successful alternative to amalgam.

Bicuspid↗
PubMed2004

The histone acetyltransferase GCN5 modulates the retrograde response and genome stability determining yeast longevity.

Transcriptional silencing decreases at both subtelomeric and silent mating-type loci and increases at the ribosomal DNA locus during the replicative life span of the yeast Saccharomyces cerevisiae . Evidence exists that epigenetic changes in the regulatory state of chromatin may be a causal factor in determining yeast longevity and that histone deacetylases play a role. The significance of histone acetylation has been examined here in more detail. Deletion of the histone acetyltransferase gene GCN5 suppressed the extension of replicative life span afforded by the induction of the retrograde response, which signals mitochondrial dysfunction and leads to changes in nuclear gene expression. It was difficult to ascribe this effect to changes in transcriptional silencing in any of the three known types of heterochromatin. However, a promoter related effect was uncovered by the participation of GCN5 in the induction of the retrograde response. Gcn5p and the retrograde signal transducer Rtg2p are components of the histone acetyltransferase coactivator complex SLIK. Rtg2p blocks the production of extrachromosomal ribosomal DNA circles when it is not engaged in transmission of the retrograde signal. Deletion of GCN5 , which disrupts the integrity of SLIK, suppressed circle accumulation. The results indicate that Gcn5p and SLIK impact the interplay between the retrograde response signal and Rtg2p with consequences for the induction of the response and circle production. Rtg2p and Gcn5p in the SLIK complex link metabolism to stress responses, chromatin-dependent gene regulation, and genome stability in yeast aging.

Base Sequence↗
PubMed1987

Evaluation of pacemaker pulse generator and patient longevity in patients aged 1 day to 20 years.

The longevity of pediatric patients requiring pacemakers and the survival rates of the implanted generators were evaluated. From January 1970 to December 1985, 96 patients aged 1 day to 20 years underwent 162 pulse generator implantation procedures. Indication for initial implantation was surgically induced heart block in 52 patients, sick sinus syndrome in 20, congenital complete heart block with symptoms of low cardiac output in 19 and tachydysrhythmia control in 5. Modal age at initial implantation was less than 1 year; median age was 5 years. During this period 90 generators were removed from service: 49 (54%) because of generator failure, 22 (24%) because the patient died, 12 (13%) because of elective upgrade at the time of lead failure or cardiac surgery, 5 (6%) because of generator pocket infection and 2 (2%) because of manufacturer's recall. Pulse generators were separated into 4 groups based upon generator technology. Group I (n = 16) were asynchronous units with mercury-zinc batteries; group II (n = 18) were single-chamber demand units with mercury-zinc batteries; group III (n = 14) were single-chamber demand units with rechargeable batteries; and group IV (n = 114) were single- or dual-chamber demand units with lithium batteries. Patient survival rate was 84% at 6 months and 70% by 109 months. There was no further decrease to the end of the study period. Six-month generator survival rate was 82% for all groups, mostly a reflection of patient deaths.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1994

Poly(ethylene glycol) on the liposome surface: on the mechanism of polymer-coated liposome longevity.

The hypothetical model is built explaining the molecular mechanism of protective action of poly(ethylene glycol) on liposomes in vivo. The protective layer of the polymer on the liposome surface is considered as a statistical 'cloud' of polymer possible conformations in solution. Computer simulation was used to demonstrate that relatively a small number of liposome-grafted molecules of hydrophilic and flexible polymer can create a dense protective conformational cloud over the liposome surface preventing opsonizing protein molecules from contacting liposome. A more rigid polymer fails to form this dense protective cloud, even when hydrophilic. Computer simulation was also used to reveal possible heterogeneity of reactive sites on a polymer-coated liposome surface, and to estimate the optimal polymer-to-lipid ratio for efficient liposome protection. Experiments have been performed with the quenching of liposome-associated fluorescent label (nitrobenzoxadiazole or fluorescein) with protein (rhodamine-ovalbumin or anti-fluorescein antibody) from solution. It was shown that poly(ethylene glycol) grafting to liposomes hinders protein interaction with the liposome surface, whereas liposome-grafted dextran (more rigid polymer) in similar quantities does not affect protein-liposome interaction. Highly-reactive and low-reactive populations of chemically identical reactive sites have been found on polymer-coated liposomes. Experimental data satisfactory confirm the suggested mechanism for the longevity of polymer-modified liposome.

Binding Sites↗
PubMed1992

Longevity of synaptic depression in the hippocampal dentate gyrus.

This study used urethane-anesthetized rats to investigate the longevity of heterosynaptically evoked depression of the monosynaptic response generated by synapses between entorhinal cortical (EC) afferents and the cells of the dentate gyrus (DG). Brief, high-frequency activation of the converging ipsilateral EC-DG input depressed the synaptic response of the contralateral EC-DG synapses without prior experimentally induced potentiation. This depression lasted for hours. Such observations are consistent with a role for heterosynaptically induced long-term depression in the encoding functions of synapses.

Animals↗
PubMed1987

Necator americanus: temperature, pH, light, and larval development, longevity, and desiccation tolerance.

The effect of incubation temperature and pH on the hatch rate of eggs of Necator americanus, and the desiccation tolerance of the resulting infective stage-3 larvae were investigated in the laboratory under controlled conditions. Hatching did not occur below 15 C and above 35 C. A 21% hatch rate was obtained at 15 C while a 10.6% hatch rate was obtained at 35 C. The highest hatch rate (93.7%) was obtained at 30 C. The optimum pH for hatching was 6.0, but the larvae did not reach the infective stage. Incubation temperature of the eggs affected the longevity and desiccation tolerance of resultant infective larvae. Larvae hatched at 30 C and maintained at 26 C under bright fluorescent light had a 50% survival time (S50) of 4 days. In the dark or shade, the S50 for larvae raised at 30 C was 5 weeks, while that of larvae hatched at 20 C was 7 weeks. Incubation temperature also affected the desiccation tolerance of larvae. Larvae developed at 20 C were more resistant to desiccation at various relative humidity values than larvae hatched at 30 C.

Animals↗
PubMed1991

Longevity of adult ventricular rat heart muscle cells in serum-free primary culture.

The study had two aims: first, to improve the longevity of isolated adult cardiomyocytes in serum-free culture, and, second, to investigate whether catecholamines which promote hypertrophy in vivo can prolong survival of isolated adult rat cardiomyocytes in serum-free culture. The basic cell culture medium consists of serum-free medium 199 with 10(-7) M insulin. In this medium 50% of the initially plated cardiomyocytes survive in elongated form for 2 days. Omission of glutamine and supplementation of the basic medium with 5 mM creatine, 2 mM carnitine and 5 mM taurine extends survival of elongated cells to 14 days. In supplemented medium, normal cell ATP content is maintained (27 nmol/mg protein after 15 days), but cells gradually atrophy and reduce their protein mass. The trophic effects of catecholamines (epinephrine, norepinephrine, phenylephrine; 10 microM, added on day 3 of culture) were investigated. After addition of catecholamines the cells spread. Spreading can be prevented by prazosin (10 microM) and phentolamine (10 microM) but not by propranolol (10 microM), indicating that spreading is stimulated via the alpha 1-adrenoreceptor. Cells also spread in the presence of the phorbol ester phorbol myristate acetate (10 microM). Catecholamines reduce the progressive cell atrophy and protein loss. With 10 microM phenylephrine, cellular ATP content remained constant at 27 nmol/mg protein until day 15. The results indicate that agents which stimulate protein kinase C (alpha 1-agonists, phorbol esters) stimulate cell spreading, protein synthesis and long-term survival of cardiomyocytes in vitro.

Animals↗
PubMed1982

Optimum conditions for growth and longevity of chick embryo fibroblasts in culture.

Chick embryo fibroblasts are often used as a model of cellular ageing in vitro. It seems important to culture these cells in optimum conditions which may not be the same as those for mammalian cells. An incubation temperature of 40 degrees C and the use of chicken serum were found to be optimum for growth and longevity of chick embryo fibroblasts in culture.

Animals↗
PubMed1984

Genetically determined conidial longevity is positively correlated with superoxide dismutase, catalase, glutathione peroxidase, cytochrome c peroxidase, and ascorbate free radical reductase activities in Neurospora crassa.

Aging of post-mitotic cells, the conidia, of Neurospora crassa is defined as the time-dependent loss of viability under a constant laboratory environment which probably resembles the organism's tropical habitat; namely, at 30 degrees C, 85-100% relative humidity under white light. Median lifespan is defined as the age at which survival of a conidial population has declined to 50% of that of a fully viable population at birth. A collection of short (age-) and long-lived (age+) mutants were previously selected from the wild-type whose median lifespan is 22 days. Thus, five groups of strains with distinct lifespans of 7, 22, 36, 50 and 60 days were defined. The purposes of the present investigation were to determine if the activities of anti-oxygenic enzymes are correlated with lifespan and to elucidate the function of the cellular longevity determinant genes. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) were highly-correlated with lifespan; whereas glutathione reductase and non-specific peroxidase activities were not correlated. The short-lived mutants were also deficient in cytochrome c peroxidase (CPX) and ascorbate free radical reductase (AFR), but not deficient in dehydroascorbate reductase. (These latter three enzymes were not examined in age+ mutants.) By isoelectric focusing analysis, the deficiencies of SOD, CAT, and GPX activities of age- mutants were defined in terms of specific isozymes. The mutants were specifically deficient in a cyanide-resistant mitochondrial isozyme of SOD. Sixteen age- genes, called the age-1 complex, were previously mapped on one arm of the seven chromosomes. On the basis of mapping and complementation data, it was inferred that the genes are spatially and functionally redundant. The hypothesis of functional redundancy is also supported by the enzyme data. Of seven mutants examined, representing seven of the age- genes, all were deficient in SOD, CAT and CPX, and six were deficient in AFR. Of four mutants examined, representing four of the genes, all were deficient in GPX. The results indicate a molecular basis for the previously observed photosensitivity of the mutants.(ABSTRACT TRUNCATED AT 400 WORDS)

Catalase↗