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PubMed1993

Acquisition of Desiccation Tolerance and Longevity in Seeds of Arabidopsis thaliana (A Comparative Study Using Abscisic Acid-Insensitive abi3 Mutants).

Two new abscisic acid (ABA)-insensitive mutants of Arabidopsis thaliana affected in the abi3 locus are described. These new mutants are severely ABA insensitive. Like the earlier described abi3-1 and the ABA-deficient and -insensitive double mutant aba,abi3, these new mutants vary in the extent of ABA-correlated physiological responses. Mutant seeds fail to degrade chlorophyll during maturation and show no dormancy, and desiccation tolerance and longevity are poorly developed. Carbohydrate accumulation as well as synthesis of LEA or RAB proteins are often suggested to be essential for acquisition of desiccation tolerance. In this work two points are demonstrated. (a) Accumulation of carbohydrates as such does not correlate with acquisition of desiccation tolerance or longevity. It is suggested that a low ratio of mono- to oligosac-charides rather than the absolute amount of carbohydrates controls seed longevity or stability to desiccation tolerance. (b) Synthesis of a few assorted proteins, which is responsive to ABA in the later part of seed maturation, is not correlated with desiccation tolerance or longevity.

Journal Article↗
PubMed2005

Implant-supported facial prostheses provided by a maxillofacial unit in a U.K. regional hospital: longevity and patient opinions.

PURPOSE: The aim of this study was to acquire information on the types and longevity of implant-retained facial prostheses and the opinions of patients on several factors related to their prostheses. MATERIALS AND METHODS: A survey of 75 maxillofacial prosthetic patients currently under treatment and review at the Maxillofacial Unit, Morriston Regional Hospital was conducted through a 23-question postal questionnaire. These patients were selected as representative of a group of individuals receiving treatment or under review for the fabrication of maxillofacial prostheses. RESULTS: Of the prosthetic replacements, 83% were ear prostheses, 8% nose, 6% eye, and 2% combination prostheses. Of the 47 respondents, 8 (17%) reported that they were currently wearing their original prostheses. The remaining 39 (83%) respondents had all been provided with at least 1 replacement prosthesis. The mean lifetime of the prostheses was found to be 14 months (range: 4-36 months). The majority of replacement prostheses in this study were provided as a result of color fade or wear of the silicone material of the previous prosthesis. Individuals with no previous experience wearing a prosthesis had an unrealistic expectation of their prosthesis longevity, with a mean value of 17.8 months. In comparison, individuals with previous experience had reduced expectations, with a mean of 14.4 months. In terms of the patients' opinions of the overall quality of their prostheses, the results demonstrated that a large number of patients were satisfied. Thirty-five patients rated their prostheses as excellent and 9 as good. At 7-12 months, 4 patients rated their prostheses as excellent and 8 as good. At 13 months, 4 patients rated their prostheses as excellent and 5 as good. CONCLUSIONS: It is important that advice be given to patients on the expected average longevity of their prostheses, together with information on factors affecting the longevity (i.e., environmental staining, cosmetics, and cleaning regimes). In this study, 26% of the replacement prostheses were provided due to color fading of the original prosthesis. This highlights the need for continuing research in the development of materials used for the construction of facial prostheses with improved properties, and in particular, improved color stability.

Adolescent↗
PubMed2000

Benefits in projected pacemaker longevity and in pacing related costs conferred by automatic threshold tracking.

The aim of this study was to calculate the battery current drain of different VVI-VVIR pulse generators, with and without automatic adjustment of stimulation output, from the same manufacturer, and obtain projections on pacemaker longevity and pacing related costs. Twenty-five patients who had received a VVIR pacemaker (Microny SR+ 2425T) with Autocapture function, an algorithm able to provide automatic adaptation of device output coupled with continuously monitored capture threshold, were analyzed. Calculations of current drain and projections of device longevity were based on diagnostic data retrieved from device memory and on comparisons of multiple programmed settings of the same device (Microny SR+ 2425T with Autocapture, Low Output [output = 2 x Autocapture threshold, but not less than 2.4 V] versus Standard Output [5 V]). In addition, devices with Autocapture but with different battery capacities (0.35 Ah and 0.79 Ah, Microny and Regency, respectively) were compared to a standard device (battery capacity = 0.78 Ah) at 2.5-V and 5-V output settings. According to a series of assumptions, Autocapture increased device longevity by 53% (Microny) and by 245% (Regency) over a 15-year follow-up with a consequent reduction in pacing related costs of 25% (Microny) and of 57% (Regency) compared to the standard settings of a VVIR device from the same manufacturer. In conclusion, pacing with constant adaptation of generator output coupled with continuous monitoring of stimulation threshold has the potential to increase generator longevity and to reduce pacing related costs as compared to a standard device from the same manufacturer.

Aged↗
PubMed1992

Restoration longevity in an Australian Defence Force population.

Replacement of restorations comprises a considerable portion of the work of most dentists. Consequently, factors that affect restoration longevity can influence the pattern of dental practice in a given community. Based on the results of research into treatment provision in the General Dental Service in Scotland, it was considered possible that factors such as the frequency with which patients were examined, and the frequency with which they changed dentists, might influence restoration longevity in other populations. Therefore, the present study was initiated to investigate the effects of these two factors in a population of 100 long-term members of the Royal Australian Air Force. No statistically significant relationship could be found between examination frequency, or frequent changes in dental practitioner, and restoration longevity. It is proposed that the large differences found in restoration longevity between this study and the Scottish study upon which it was based, may be due in part to the differing modes of remuneration of the dentists in the two studies.

Adult↗
PubMed2005

Control of multidrug resistance gene mdr1 and cancer resistance to chemotherapy by the longevity gene sirt1.

Irreversible growth arrest (also called senescence) has emerged recently as a tumor suppressor mechanism and a key determinant of cancer chemotherapy outcome. Previous work from our laboratory suggested that the cellular ability to undergo or to escape senescence dictates its fate to become drug-sensitive or drug-resistant, respectively. In the present study, we made the hypothesis that longevity genes, by virtue of their ability to inhibit senescence, may contribute to the onset of drug resistance. We report that expression of the longevity gene sirt1 increased both at the RNA and protein levels in all the five drug-resistant cell lines tested when compared with their drug-sensitive counterparts. In addition, biopsies from cancer patients treated with chemotherapeutic agents also expressed high levels of this molecule. These changes were specific for sirt1 because the expression of other members of its family was not affected. More importantly, small interfering RNA-mediated down-regulation of sirt1 significantly reversed the resistance phenotype and reduced expression of the multidrug resistance molecule P-glycoprotein. This was further confirmed by ectopic overexpression of sirt1, which induced expression of P-glycoprotein and rendered cells resistant to doxorubicin. Collectively, these findings uncovered a novel function for the longevity gene sirt1 as a potential target for diagnosis and/or treatment of cancer resistance to chemotherapy. They also describe a proof of principle that signaling pathways implicated in longevity may share similarities with those leading to development of drug resistance in cancer.

Bone Neoplasms↗
PubMed1996

Liposome longevity and stability in circulation: effects on the in vivo delivery to tumors and therapeutic efficacy of encapsulated anthracyclines.

The effect of liposome composition on drug delivery to tumors and therapeutic efficacy of liposome-encapsulated anthracyclines was investigated in two murine tumor models: an ascitic tumor (J6456 lymphoma) and a solid carcinoma (M-109). Longevity in circulation correlated positively with high drug levels in the extracellular (ascitic) tumor fluid and with delayed peak tumor levels. Using polyethylene-glycol(PEG)-coated liposomes, liposome stability (drug retention) was found to be an important determinant of therapeutic efficacy, as indicated by the superior survival conferred by high Tm phosphatidylcholines (hydrogenated, dipalmitoyl) over low Tm (egg phosphatidyl-choline). Replacing PEG with another negatively-charged surface headgroup (phosphatidyl-glycerol, phosphatidyl-inositol) resulted in relatively shorter longevity in circulation of the liposome-associated drug, but no detectable differences in anti-tumor efficacy. When neither the surface charged headgroup nor the PEG coating are present, the resulting drug formulation was significantly less effective than PEG and phosphatidylinositol-based formulations in both tumor models. In conclusion, longevity in circulation, as obtained with PEG coating, tends to improve the therapeutic efficacy of liposome-encapsulated anthracyclines. The current therapeutic models were however unable to detect differences between the therapeutic activity of PEG and other liposome formulations with relatively small differences in circulation longevity.

Animals↗
PubMed1991

Estimating employment longevity of nursing personnel.

Health-care managers require estimates of employment longevity (time from hire to termination) for use in assessing future pension obligations, costs that are functions of longevity and experience such as fringe benefits, and workforce stability. Existing approaches for obtaining these estimates are problematic, complicated by time-varying data or infeasible data requirements, and may result in biased estimators. Renewal theory is presented as a model for estimating the complete distribution of the longevity of a population when the only data available is censored (i.e., time on the job of current employees). The model's ability to estimate nursing personnel longevity is demonstrated.

Employment↗
PubMed1990

Longevity of posterior restorations.

The efficacy of restorative dentistry is dependent on a number of factors, including material quality, operator proficiency and the oral hygiene of the patient. The sum effect of all factors can be measured by recording the longevity of the restorations. Many studies focus on the age of restorations at the time of failure, others include the longevity of restorations which remain in situ. The surveys may be either longitudinal, prospective or retrospective, or cross-sectional retrospective studies of dental records. They are all hampered by the lack of uniform criteria defining when to place and replace restorations and by variations in decision-making between clinicians. The present review paper shows that the longevity of amalgam restorations has been studied most frequently. About 50 per cent of all amalgam restorations exceed 8-10 years in age, cast gold restorations may last longer and multisurfaced composite restorations have a shorter life-span. Glass ionomer cements lack the physical properties needed for large posterior restorations. The results of detailed longevity studies should be the basis for selection of materials and techniques in operative/conservative treatment. The cost of dental treatment should be related to the expected lifetime of the tooth rather than to the immediate cost of a simple restoration.

Bicuspid↗
PubMed1994

Divergent roles of RAS1 and RAS2 in yeast longevity.

Individual cells of the yeast Saccharomyces cerevisiae have a limited replicative life-span. The role of the genes RAS1 and RAS2 in yeast longevity was examined. Over-expression of RAS2 led to a 30% increase in the life-span on average and postponed the senescence-related increase in generation time seen during yeast aging. No life-span extension was obtained by overexpression of RAS1. However, deletion of RAS1 prolonged the life-span. These results suggest that RAS1 and RAS2 play reciprocal roles in determining yeast longevity. RAS1 and RAS2 mRNA and protein levels declined with replicative age, suggesting a diminishing impact on yeast longevity. The major known pathway through which Ras proteins function in yeast involves stimulation of adenylate cyclase. No evidence for a life-span-extending effect of elevated intracellular cAMP was found. Indeed, high intracellular cAMP was associated with curtailed life-span. A similar decrease in life-span was found on disruption of BCY1, which codes for the regulatory subunit of protein kinase A, the downstream target of cAMP. Importantly, overexpression of an effector domain mutant of RAS2, defective in stimulation of adenylate cyclase, prolonged life-span to the same extent as the wild-type gene, suggesting that the cAMP pathway is neither sufficient nor necessary for increased longevity.

Adenylyl Cyclases↗
PubMed1996

Reprogramming pacemakers enhances longevity and is cost-effective.

BACKGROUND: Historically, the majority of pulse generators implanted in the United States remain at the nominal programmed settings from the time of implant. While these nominal settings typically allow a sufficient safety margin to prevent later loss of capture with potential chronic threshold rise, the pulse generator with significant use would not be expected to last longer than that predicted by the manufacturer. However, improvements in lead technology have resulted in significantly lower chronic capture thresholds, which would permit lower programmable output settings while still allowing acceptable safety margins. Such changes could result in a significant reduction in long-term battery drain and translate into longer generator life. METHODS AND RESULTS: One hundred eighty consecutive patients undergoing implantation of permanent pacemakers at our institution were studied to determine the impact of reprogramming on pulse generator longevity and cost. Of these patients, 122 completed 6 months of follow-up at our institution and had pulse generators implanted that were capable of measuring battery current. We compared the estimated longevity based on battery current at nominal settings with that based on settings achieved in follow-up. The final settings were determined by the patient's physician using standard safety margins. The predicted longevity was 6.95 +/- 1.59 years at nominal implant settings and 11.16 +/- 2.71 years at final programmed settings (P < .001). Therefore, reprogramming extends the estimated pulse generator longevity by 4.25 +/- 2.14 years (64%) at a mean cost of $110 per patient (+37 per year extended). CONCLUSIONS: Reprogramming of permanent pacemakers is efficacious and cost-effective.

Cost-Benefit Analysis↗
PubMedDate not supplied

Effects of varying intervals between heparin flushes on pediatric catheter longevity.

The effectiveness of 4-, 6-, and 8-hour heparin flushing intervals on the logevity of 22- and 24-gauge intermittent i.v. catheters was examined in 83 pediatric patients. Catheters lasted 18-20 hours longer with 6- and 8-hour flushing intervals than with 4-hour intervals. A comparison of 22- and 24-gauge catheters revealed that there was no difference in longevity based on size. Also, use of medications did not affect catheter longevity. Age differences in catheter longevity were noted (greater longevity in older children) and is a result that needs further research. Based on the results of this study, if longer flushing intervals were used, fewer i.v.'s would have to be restarted and nursing time caring for i.v.'s would be decreased.

Adolescent↗
PubMed2006

Is human longevity a consequence of cultural change or modern biology?

Increased longevity, expressed as the number of individuals surviving to older adulthood, represents a key way that Upper Paleolithic Europeans differ from earlier European (Neandertal) populations. Here, we address whether longevity increased as a result of cultural/adaptive change in Upper Paleolithic Europe, or whether it was introduced to Europe as a part of modern human biology. We compare the ratio of older to younger adults (OY ratio) in an early modern human sample associated with the Middle Paleolithic from Western Asia with OY ratios of European Upper Paleolithic moderns and penecontemporary Neandertals from the same region. We also compare these Neandertals to European Neandertals. The difference between the OY ratios of modern humans of the Middle and Upper Paleolithic is large and significant, but there is no significant difference between the Neandertals and early modern humans of Western Asia. Longevity for the West Asian Neandertals is significantly more common than for the European Neandertals. We conclude that the increase in adult survivorship associated with the Upper Paleolithic is not a biological attribute of modern humans, but reflects important cultural adaptations promoting the demographic and material representations of modernity.

Adult↗
PubMed2004

Power of non-parametric linkage analysis in mapping genes contributing to human longevity in long-lived sib-pairs.

This report investigates the power issue in applying the non-parametric linkage analysis of affected sib-pairs (ASP) [Kruglyak and Lander, 1995: Am J Hum Genet 57:439-454] to localize genes that contribute to human longevity using long-lived sib-pairs. Data were simulated by introducing a recently developed statistical model for measuring marker-longevity associations [Yashin et al., 1999: Am J Hum Genet 65:1178-1193], enabling direct power comparison between linkage and association approaches. The non-parametric linkage (NPL) scores estimated in the region harboring the causal allele are evaluated to assess the statistical power for different genetic (allele frequency and risk) and heterogeneity parameters under various sampling schemes (age-cut and sample size). Based on the genotype-specific survival function, we derived a heritability calculation as an overall measurement for the effect of causal genes with different parameter settings so that the power can be compared for different modes (dominant, recessive) of inheritance. Our results show that the ASP approach is a powerful tool in mapping very strong effect genes, both dominant and recessive. To map a rare dominant genetic variation that reduces hazard of death by half, a large sample (above 600 pairs) with at least one extremely long-lived (over age 99) sib in each pair is needed. Again, with large sample size and high age cut-off, the method is able to localize recessive genes with relatively small effects, but the power is very limited in case of a dominant effect. Although the power issue may depend heavily on the true genetic nature in maintaining survival, our study suggests that results from small-scale sib-pair investigations should be referred with caution, given the complexity of human longevity.

Age Factors↗
PubMed1985

Environmental and genetic factors that influence immunity and longevity in mice.

Many different theoretical approaches may be taken toward understanding the association between aging and immunologic malfunction. The leading theory is based on the natural phenomenon of thymic involution and argues that the T-dependent lymphoid system is genetically programmed to decline in effectiveness, possibly through altered endocrine and central nervous system controls. The "thymic time clock" theory of aging is strongly supported by the consistent finding of defective cellular immunity functions in aged humans and animals and an associated development of the age-related diseases. In several animal models, including autoimmune-prone strains, high spontaneous tumor incidence strains, and normal long-lived strains, it has been possible to forestall the development of the major diseases of aging and extend longevity by restricting diet. The predominant effect of dietary restriction is prolongation of immunologic vigor and retardation of the immunologic dysfunction that normally occurs with age. Studies on environmental factors affecting longevity such as these and others which demonstrate a complex interaction between genes influencing longevity underscore the complexity and challenge of aging research.

Aging↗
PubMed1994

Longevity and antioxidant enzymes, non-enzymatic antioxidants and oxidative stress in the vertebrate lung: a comparative study.

It has been proposed that antioxidants can be longevity determinants in animals. However, no comprehensive study has been conducted to try to relate free radicals with maximum life span. This study compares the lung tissue of various vertebrate species--amphibia, mammals and birds--showing very different and well known maximum life spans and life energy potentials. The lung antioxidant enzymes superoxide dismutase, catalase, Se-dependent and non-Se-dependent glutathione peroxidases, and glutathione reductase showed significantly negative correlations with maximum life span. The same was observed for the lung antioxidants, reduced glutathione and ascorbate. It is concluded that a generalized decrease in tissue antioxidant capacity is a characteristic of longevous species. It is suggested that a low rate of free radical recycling (free-radical generation and scavenging) can be an important factor involved in the evolution of high maximum animal longevities. A low free-radical production could be responsible for a low rate of damage at critical sites such as mitochondrial DNA.

Animals↗
PubMed2004

Association between longevity and cytokine gene polymorphisms. A study in Sardinian centenarians.

BACKGROUND AND AIMS: Human longevity seems to be directly correlated with optimal functioning of the immune system, suggesting that some genetic determinants of longevity reside in those polymorphisms for the immune system genes which regulate immune-inflammatory responses, in particular cytokine gene polymorphisms. The frequency of -174C single nucleotide polymorphism (SNP) in the promoter region of the interleukin (IL)-6 gene is increased in Italian male centenarians. Moreover, the frequency of -1082G SNP at the 5' flanking region of the IL-10 gene coding sequence is increased among male centenarians, and that of +874A SNP at the interferon (IFN)-gamma gene was found more frequently in female centenarians. These findings indicate that different alleles at different cytokine gene codings for pro- (IL-6, IFN-gamma) or anti-inflammatory (IL-10) cytokines may affect the individual life-span expectancy, influencing the type and intensity of immune-inflammatory responses against environmental stressors. METHODS: In the present study, we analyzed these IL-6, IL-10 and IFN-gamma gene polymorphisms in 112 (36 male, 76 female) centenarians from the island of Sardinia, whose population shows a genetic background quite different from that of mainland Italy, as well as in 137 sixty-year-old controls from the same geographic area. RESULTS: No significant differences were observed on analyzing IL-6, IL-10 and IFN-gamma polymorphism frequencies among centenarians and controls, either on the whole and when the data were analyzed according to gender. CONCLUSIONS: These data indicate that gene polymorphisms of cytokines playing a major regulatory role in the inflammatory response do not affect life expectancy in the Sardinian population. Thus, cytokine/longevity associations have a population-specific component, being affected by the population-specific gene pool as well as by gene-environment interactions, behaving as survival rather than longevity genes.

Aged↗
PubMed2003

Association analysis of the SHC1 gene locus with longevity in the Japanese population.

The SHC1 gene encodes a signaling and transforming protein that has been implicated in the aging process in worms and mammals. In this study we examined 230 Japanese centenarians and 180 healthy younger controls and looked at the SHC1 locus as a candidate region that may be associated with longevity. We identified 12 single nucleotide polymorphisms (SNPs) within a 10-kb region encompassing the entire SHC1 gene from the DNA of 30 centenarians and 24 healthy younger controls. Five SNPs, including three nonsynonymous sites, lay within coding elements, six were located within introns, and one was in the 3' untranslated region. All of these SNPs were relatively rare, with a minor allele frequency of less than 5% in our subjects. A pairwise linkage disequilibrium analysis using the r2 statistic showed that two of the SNP pairs are in tight linkage disequilibrium at this locus. We investigated the possible association of SHC1 with longevity using association analyses with allelotypes and haplotypes but found that the SNPs identified in SHC1 had no impact on longevity for Japanese centenarians.

Adaptor Proteins, Signal Transducing↗
PubMed2000

New polymorphisms in the human poly(ADP-ribose) polymerase-1 coding sequence: lack of association with longevity or with increased cellular poly(ADP-ribosyl)ation capacity.

Poly(ADP-ribose) polymerase-1 (PARP-1) encoded by the PARP-1 gene, is a ubiquitous and abundant DNA-binding protein involved in the cellular response to various genotoxic agents. In a previous study we showed that maximal oligonucleotide-stimulated poly(ADP-ribosyl)ation was significantly higher in permeabilised lymphoblastoid cell lines from a French population of centenarians compared with controls aged 20-70 years, supporting the notion that longevity is associated with a genetically determined, high poly(ADP-ribosyl)ation capacity. Here, we describe four new genetic polymorphisms, three of which represent silent nucleotide variants (C402T, T1011C, G1215A), and one of which leads to a valine762-to-alanine exchange (T2444C). We undertook an association study between two of these polymorphisms and human longevity or poly(ADP-ribosyl)ation capacity in permeabilised lymphoblastoid cells. By analysing 648 DNA samples from a French population (324 centenarians and 324 controls) by fluorescent-allele-specific PCR, we showed the absence of any significant enrichment of any of the genotypes in the study of centenarians versus controls. Furthermore, we studied genotype distributions from individuals who had previously been tested for poly(ADP-ribosyl)ation capacity. None of the genotype combinations at any polymorphic site studied could be related to a high or low level of poly(ADP-ribosyl)ation capacity. Together, these results strongly suggest that the longevity-related differences in the poly(ADP-ribosyl)ation capacity of human lymphoblastoid cell lines cannot be explained by genetic polymorphisms in the PARP-1 coding sequence and that other mechanisms have to be considered as potential regulators of specific poly(ADP-ribosyl)ation capacity.

Aged↗