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Variable effects of vitamin E on Drosophila longevity.

Vitamin E has been used widely in invertebrate experiments where it usually acts to prolong life span. Conversely in vertebrates it has been less successful. In some cases, experiments in rodents show no effect of vitamin E on longevity. Consequently, the suggestion has been made that anti-oxidants do not effect ageing in vertebrates. In more extensive experiments with Drosophila melanogaster, vitamin E exerted both life span extending and toxic effects. At 20 micro g/ml, the life span was increased by 16%, although there was no effect at higher or lower concentrations. At 200 micro g/ml, vitamin E protected Drosophila against paraquat toxicity. At this concentration, vitamin E had no effect on longevity in one set of experiments, and shortened the life span in another set. Apparent toxicity of vitamin E was also observed in behavior experiments. We suggest that inactivity of vitamin E that has been reported by some authors is due to antagonistic actions of a toxic effect and a beneficial anti-oxidant action. This complex response to vitamin E will limit its use for clinical and investigative work on ageing.

Aging↗

Longevity of silicone and polyurethane catheters in long-term enteral feeding via percutaneous endoscopic gastrostomy.

BACKGROUND: As percutaneous endoscopic gastrostomy (PEG) is often used for many months or years, the longevity of the feeding tubes plays an important role in the global outcome and costs of PEG. AIM: A retrospective study to evaluate the longevity of silicone and polyurethane PEG catheters. METHODS: The records of 297 patients who were fed via PEG for over 90 days were evaluated. The material of the PEG catheter, duration of follow-up, local complications, need to remove PEG because of tube deterioration or local complications and time from PEG placement to PEG removal were recorded and compared. RESULTS: Two hundred and twenty-eight patients had polyurethane and 69 had silicone PEG catheters. The follow-up ranged from 116 to 3207 days for the polyurethane group and from 98 to 1861 days for the silicone group. No differences were observed in either local complications or PEG removal because of local complications. Tube deterioration causing PEG removal occurred in 36 of the 228 polyurethane PEG catheters and in 25 of the 69 silicone PEG catheters (P = 0.0005). Tube deterioration occurred significantly earlier in the 25 silicone catheters than in the 36 polyurethane catheters. The mean time from PEG placement to PEG removal was 287 days (95% confidence interval, 239-335) for silicone tubes and 573.9 days (95% confidence interval, 425-723) for polyurethane tubes (P = 0.0024). CONCLUSION: Polyurethane PEG catheters seem to be more resistant to deterioration than silicone PEG catheters, and at present they should be preferred for long-term enteral feeding via PEG.

Adolescent↗

Clinical longevity of resin-bonded bridges bonded using a vinyl-thiol primer.

The purpose of this study is to clinically confirm the adhesive effect of a vinyl-thiol primer (V-Primer) for precious alloys. Further, we examined the failure of resin-bonded bridges (RBBs) in order to improve the clinical longevity of RBBs, and to analyse the causes of failure. Twenty-six RBBs were bonded with V-primer and Super Bond C & B between May 1987 and December 1997 in the Dental Clinic of the Health Sciences University of Hokkaido. The RBBs were made of silver-palladium-gold alloy or metal-ceramic gold alloys. V-primer was effective in bonding Super Bond C & B to the RBBs made of silver-palladium-gold alloys. Ten prostheses had functioned satisfactorily for 8-11 years. However, six of the 26 RBBs had become detached. In four of the six failed RBBs, the type of bond failure was a mixture fracture in the resin-enamel interface. Our results suggest that: (1) V-primer is effective on RBBs made of silver-palladium-gold alloys. (2) Mechanical retention is necessary for retainers to improve the longevity of RBBs when the V-primer is applied to RBBs made of precious alloys without copper. (3) The RBB should not be applied to abutment teeth that have differences in tooth mobility.

Adhesives↗

Symposium on mechanisms of ageing and longevity.

The Symposium on 'Mechanisms of Ageing and Longevity' was held at the Royal Free Campus, Royal Free and University College Medical School, London, on 17 September 1999. It was organised and sponsored by the Anatomical Society of Great Britain and Northern Ireland with generous contributions from BBSRC, AgeNet and Research into Ageing.THE SYMPOSIUM WAS ORGANISED AS A RESULT OF RECENT DISCOVERIES IN TWO PRINCIPAL AREAS: the genetics of longevity regulation in the nematode worm, Caenorhabditis elegans, and the cell biology of ageing in mammalian cells. Papers were presented covering the role of insulin-like signalling, free radical damage and caloric restriction in ageing of invertebrate and mammalian systems. One of the principal aims was to examine the idea that a genetically conserved signalling pathway might regulate ageing processes at both a cellular and an organismal level.

Journal Article↗

Functional capacity and fertilizing longevity of frozen-thawed scimitar-horned oryx (Oryx dammah) spermatozoa in a heterologous in vitro fertilization system.

This study was conducted to determine if cryopreservation and thawing reduces the quality of scimitar-horned oryx spermatozoa and thus might be responsible for sub-optimal artificial insemination (Al) efficiency. Functional capacity of frozen thawed oryx spermatozoa was compared in a heterologous bovine in vitro fertilization (IVF) system after being prepared by four methods. Fertilizing longevity was also assessed after thawing and pre-incubating spermatozoa for 12 or 24 h before IVF. Sperm characteristics (viability, morphology, acrosomal and capacitation status) were superior for samples prepared by Percoll centrifugation and standard swim-up compared with microdrop swim-up and wash methods. Regardless of variation in sperm characteristics over time, fertilization success and embryo development were high and did not differ among treatments. Fertilization and cleavage success for spermatozoa pre-incubated for 12 h before IVF were comparable with that achieved with non-incubated spermatozoa. Even 24 h after thawing, spermatozoa were capable of fertilizing oocytes, but percentage fertilization and embryo cleavage were significantly lower than for spermatozoa pre-incubated for 12 h. Overall, functional capacity of oryx spermatozoa after thawing appears comparable with that of domestic bull spermatozoa. When used for Al, frozen-thawed oryx spermatozoa should be capable of fertilizing oocytes in females ovulating 12 or even 24 h after insemination, providing sperm transport mechanisms are adequate. The functional capacity and fertilizing longevity of oryx sperm after thawing is high, and therefore unlikely to be responsible for decreased Al efficiency in the scimitar-horned oryx.

Animals↗

Gene elements that affect the longevity of rbcL sequence-containing transcripts in Chlamydomonas reinhardtii chloroplasts.

The chloroplast gene rbcL encodes the large subunit of the CO(2)-fixing enzyme ribulose-bisphosphate carboxylase. In previous work a target for photo-accelerated degradation of Chlamydomonas reinhardtii rbcL transcripts in vivo was found to lie within the first 63 nucleotides, and a sequence element required for increasing the longevity of transcripts of rbcL-reporter genes was found to occur between nucleotides 170 and 350. Photo-accelerated degradation of rbcL transcripts has been found to require nucleotides 21 to 41. Transcript nucleotides lying between 329 and 334 and between 14 and 27 are essential for stabilizing transcripts in vivo; mutations in either region reduce the longevity of transcripts. It is postulated that the effectiveness of photo-accelerated endonuclease attacks on the nucleotide 21 to 41 region is reduced by physical blockage or distortion of the target sequence by interacting proteins that associate with nucleotides in the 14 to 27 and 329 to 334 regions of the transcripts. Both the nucleotide +329 to +334 stabilizing sequence of rbcL and a transcription enhancing sequence that lies between +126 and +170 encode well conserved (cyanobacteria through angiosperms) amino acid sequences; the evolution of expression control elements within the protein coding sequence of rbcL is considered.

Animals↗

Cytokinin-mediated control of leaf longevity by AHK3 through phosphorylation of ARR2 in Arabidopsis.

Cytokinins are plant hormones with profound roles in growth and development, including control of leaf longevity. Although the cytokinin signal is known to be perceived by histidine kinase receptors, the underlying molecular mechanism and specificity of the receptors leading to delayed leaf senescence have not yet been elucidated. Here, we found that AHK3, one of the three cytokinin receptors in Arabidopsis, plays a major role in controlling cytokinin-mediated leaf longevity through a specific phosphorylation of a response regulator, ARR2. This result was obtained through identification of a gain-of-function Arabidopsis mutant that shows delayed leaf senescence because of a missense mutation in the extracellular domain of AHK3. A loss-of-function mutation in AHK3, but not of the other cytokinin receptors, conferred a reduced sensitivity to cytokinin in cytokinin-dependent delay of leaf senescence and abolished cytokinin-dependent phosphorylation of ARR2. Consistently, transgenic overexpression of wild-type, but not an unphosphorylatable mutant ARR2, led to delayed senescence of leaves.

Aging↗

Mitochondrial longevity in vitro: the retention of respiratory control.

Isolated mitochondria were maintained metabolically active and coupled, i.e., capable of respiratory control, for several hours at 25 degrees C. An increase in respiratory control generally occurred during the first 4-8 hr of incubation followed thereafter by a decline. Longevity is a dynamic function as evidenced by its dependency on substrate and cofactors, thiamine pyrophosphate, in particular. Magnesium was also essential to longevity; coenzyme A, bovine serum albumin, and reducing agents were not. The findings are discussed in terms of cytoplasmic-mitochondrial interrelationships and mitochondrial autonomy.

Adenine Nucleotides↗

The dihydrolipoamide acetyltransferase is a novel metabolic longevity factor and is required for calorie restriction-mediated life span extension.

Calorie restriction (CR) extends life span in a wide variety of species. Recent studies suggest that an increase in mitochondrial metabolism mediates CR-induced life span extension. Here we present evidence that Lat1 (dihydrolipoamide acetyltransferase), the E2 component of the mitochondrial pyruvate dehydrogenase complex, is a novel metabolic longevity factor in the CR pathway. Deleting the LAT1 gene abolishes life span extension induced by CR. Overexpressing Lat1 extends life span, and this life span extension is not further increased by CR. Similar to CR, life span extension by Lat1 overexpression largely requires mitochondrial respiration, indicating that mitochondrial metabolism plays an important role in CR. Interestingly, Lat1 overexpression does not require the Sir2 family to extend life span, suggesting that Lat1 mediates a branch of the CR pathway that functions in parallel to the Sir2 family. Lat1 is also a limiting longevity factor in nondividing cells in that overexpressing Lat1 extends cell survival during prolonged culture at stationary phase. Our studies suggest that Lat1 overexpression extends life span by increasing metabolic fitness of the cell. CR may therefore also extend life span and ameliorate age-associated diseases by increasing metabolic fitness through regulating central metabolic enzymes.

Cell Cycle↗

Elevated CO22 and Leaf Longevity in the C44 Grassland-Dominant Andropogon gerardii.

In central U.S. grasslands, plant and ecosystem responses to elevated CO2 are most pronounced when water availability is limited. In a northeast Kansas grassland, responses to elevated CO2 in leaf area, number, development, and longevity were quantified for the tallgrass prairie dominant, Andropogon gerardii. Plants were grown in open-top chambers (OTCs) modified to limit water availability and to maximize responses to elevated CO2. In OTCs with elevated (x2 ambient) levels of CO2, aboveground biomass production and leaf water potentials were increased significantly compared with those of plants in OTCs with ambient CO2. There were no differences in leaf area or leaf number per tiller in A. gerardii in elevated compared with ambient OTCs. However, leaf area in adjacent unchambered plots with greater water availability was significantly higher than in the OTCs. The time required for developing leaves to achieve maximum leaf area was reduced by 29%, and the period of time until leaves senesced was increased by 20% for plants exposed to elevated compared with ambient CO2. Thus, leaves of this C4 grass species expanded more rapidly (6 d) and remained green longer (9 d) when exposed to elevated CO2. Such CO2-mediated increases in leaf longevity in the dominant species may allow this grassland to respond more opportunistically to temporally variable rainfall patterns in high-CO2 environments. These responses should be included in leaf-based simulation models that attempt to mechanistically link physiological alterations to predicted canopy responses to increased CO2.

Journal Article↗

Reproductive longevity and increased life expectancy.

BACKGROUND: Female life expectancy in developed countries has increased by 30 years in the twentieth century. AIM: To determine if there has been an increase in reproductive longevity. METHODS: We analysed age-specific fertility data from birth statistics for the USA, Canada, Japan, France, Sweden, the UK and Australia. RESULTS: Since 1940, birth rates for women aged 35 and over have declined. Among women aged 50 years and older, there has been no increase in births. Fertility rates in 1990 were 0.0 to 0.044 per 1000 women, with total numbers ranging from 0 to 60 births. CONCLUSION: The fertile years have not been prolonged in the cohort of women whose life expectancy has increased so dramatically this century. This suggests that reproductive senescence is tightly controlled and not extended by factors that enhance female longevity. Other physiological mechanisms may also be fixed within narrow age limits.

Adult↗

Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans.

The nematode Caenorhabditis elegans responds to overcrowding and scarcity of food by arresting development as a dauer larva, a nonfeeding, long-lived, stress-resistant, alternative third-larval stage. Previous work has shown that mutations in the genes daf-2 (encoding a member of the insulin receptor family) and age-1 (encoding a PI 3-kinase) result in constitutive formation of dauer larvae (Daf-c), increased adult longevity (Age), and increased intrinsic thermotolerance (Itt). Some daf-2 mutants have additional developmental, behavioral, and reproductive defects. We have characterized in detail 15 temperature-sensitive and 1 nonconditional daf-2 allele to investigate the extent of daf-2 mutant defects and to examine whether specific mutant traits correlate with each other. The greatest longevity seen in daf-2 mutant adults was approximately three times that of wild type. The temperature-sensitive daf-2 mutants fell into two overlapping classes, including eight class 1 mutants, which are Daf-c, Age, and Itt, and exhibit low levels of L1 arrest at 25.5 degrees. Seven class 2 mutants also exhibit the class 1 defects as well as some or all of the following: reduced adult motility, abnormal adult body and gonad morphology, high levels of embryonic and L1 arrest, production of progeny late in life, and reduced brood size. The strengths of the Daf-c, Age, and Itt phenotypes largely correlated with each other but not with the strength of class 2-specific defects. This suggests that the DAF-2 receptor is bifunctional. Examination of the null phenotype revealed a maternally rescued egg, L1 lethal component, and a nonconditional Daf-c component. With respect to the Daf-c phenotype, the dauer-defective (Daf-d) mutation daf-12(m20) was epistatic to daf-2 class 1 alleles but not the severe class 2 alleles tested. All daf-2 mutant defects were suppressed by the daf-d mutation daf-16(m26). Our findings suggest a new model for daf-2, age-1, daf-12, and daf-16 interactions.

Adaptation, Physiological↗

SOD2 functions downstream of Sch9 to extend longevity in yeast.

Signal transduction pathways inactivated during periods of starvation are implicated in the regulation of longevity in organisms ranging from yeast to mammals, but the mechanisms responsible for life-span extension are poorly understood. Chronological life-span extension in S. cerevisiae cyr1 and sch9 mutants is mediated by the stress-resistance proteins Msn2/Msn4 and Rim15. Here we show that mitochondrial superoxide dismutase (Sod2) is required for survival extension in yeast. Deletion of SOD2 abolishes life-span extension in sch9Delta mutants and decreases survival in cyr1:mTn mutants. The overexpression of Sods--mitochondrial Sod2 and cytosolic CuZnSod (Sod1)--delays the age-dependent reversible inactivation of mitochondrial aconitase, a superoxide-sensitive enzyme, and extends survival by 30%. Deletion of the RAS2 gene, which functions upstream of CYR1, also doubles the mean life span by a mechanism that requires Msn2/4 and Sod2. These findings link mutations that extend chronological life span in S. cerevisiae to superoxide dismutases and suggest that the induction of other stress-resistance genes regulated by Msn2/4 and Rim15 is required for maximum longevity extension.

Aconitate Hydratase↗

Rtg2 protein links metabolism and genome stability in yeast longevity.

Mitochondrial dysfunction induces a signaling pathway, which culminates in changes in the expression of many nuclear genes. This retrograde response, as it is called, extends yeast replicative life span. It also results in a marked increase in the cellular content of extrachromosomal ribosomal DNA circles (ERCs), which can cause the demise of the cell. We have resolved the conundrum of how these two molecular mechanisms of yeast longevity operate in tandem. About 50% of the life-span extension elicited by the retrograde response involves processes other than those that counteract the deleterious effects of ERCs. Deletion of RTG2, a gene that plays a central role in relaying the retrograde response signal to the nucleus, enhances the generation of ERCs in cells with (grande) or in cells without (petite) fully functional mitochondria, and it curtails the life span of each. In contrast, overexpression of RTG2 diminishes ERC formation in both grandes and petites. The excess Rtg2p did not augment the retrograde response, indicating that it was not engaged in retrograde signaling. FOB1, which is known to be required for ERC formation, and RTG2 were found to be in converging pathways for ERC production. RTG2 did not affect silencing of ribosomal DNA in either grandes or petites, which were similar to each other in the extent of silencing at this locus. Silencing of ribosomal DNA increased with replicative age in either the presence or the absence of Rtg2p, distinguishing silencing and ERC accumulation. Our results indicate that the suppression of ERC production by Rtg2p requires that it not be in the process of transducing the retrograde signal from the mitochondrion. Thus, RTG2 lies at the nexus of cellular metabolism and genome stability, coordinating two pathways that have opposite effects on yeast longevity.

DNA, Ribosomal↗

Stomatal responses to drought at a Mediterranean site: a comparative study of co-occurring woody species differing in leaf longevity.

We studied stomatal responses to decreasing predawn water potential (Psipd) and increasing leaf-to-air water vapor pressure difference (VPD) of co-occurring woody Mediterranean species with contrasting leaf habits and growth form. The species included two evergreen oaks (Quercus ilex subsp. ballota (Desf.) Samp. and Q. suber L.), two deciduous oaks (Q. faginea Lam. and Q. pyrenaica Willd.) and two deciduous shrubs (Pyrus bourgaeana Decne. and Crataegus monogyna Jacq.). Our main objective was to determine if stomatal sensitivity is related to differences in leaf life span and leaf habit. The deciduous shrubs had the least conservative water-use characteristics, with relatively high stomatal conductance and low stomatal sensitivity to soil and atmospheric drought. As a result, Psipd decreased greatly in both species during the growing season, resulting in early leaf abscission in the summer. The deciduous oaks showed intermediate water-use characteristics, having maximum stomatal conductances and CO2 assimilation rates similar to or even higher than those of the deciduous shrubs. However, they had greater stomatal sensitivity to soil drying and showed less negative Psipd values than the deciduous shrubs. The evergreen oaks, and especially the species with the greatest leaf longevity, Q. ilex, exhibited the most conservative water-use behavior, having lower maximum stomatal conductances and greater sensitivity to VPD than the deciduous species. As a result, Psipd decreased less during the growing season in the evergreens than in the deciduous species, which may contribute to greater leaf longevity by avoiding irreversible damage during the summer drought. However, the combination of low maximum CO2 assimilation rates and high stomatal sensitivity to drought must have a negative impact on the final carbon budget of leaves with a long life span.

Crataegus↗

Mammalian metabolism, longevity and parasite species richness.

Basal metabolic rate (BMR) scales allometrically with body mass in mammals, but the reasons why some species have higher or lower metabolic rates than predicted from their body mass remain unclear. We tested the idea that parasite species richness may be a contributory factor by performing a comparative analysis on 23 species of mammals for which data were available on parasite species richness, BMR, body mass and two potentially confounding variables, i.e. host density and host longevity. Parasite species richness was positively correlated with BMR and negatively correlated with host longevity independent of body mass.

Animals↗

LAG2, a gene that determines yeast longevity.

Saccharomyces cerevisiae has a limited life span, measured by the reproductive capacity of the individual cell. Several genes that are differentially expressed during the yeast life span have been isolated. One of these genes, LAG2, has been characterized for its role in longevity. LAG2 is preferentially expressed in young cells. It encodes a predicted 680 amino acid protein with a putative transmembrane helix. The sequences does not show significant similarity to any other DNA or protein sequences in the databases. Deletion of LAG2 in a haploid strain did not affect growth, but it resulted in a 50% decrease in the mean and maximum life span. When LAG2 was overexpressed, the mean and maximum life span of the yeasts was extended by about 36% and 54%, respectively. These results indicate that this is a longevity-assurance gene in yeast.

Amino Acid Sequence↗

Homologs of the yeast longevity gene LAG1 in Caenorhabditis elegans and human.

LAG1 is a longevity gene, the first such gene to be identified and cloned from the yeast Saccharomyces cerevisiae. A close homolog of this gene, which we call LAC1, has been found in the yeast genome. We have cloned the human homolog of LAG1 with the ultimate goal of examining its possible function in human aging. In the process, we have also cloned a homolog from the nematode worm Caenorhabditis elegans. Both of these homologs, LAG1Hs and LAG1Ce-1, functionally complemented the lethality of a lag1delta lac1delta double deletion, despite low overall sequence similarity to the yeast proteins. The proteins shared a short sequence, the Lag1 motif, and a similar transmembrane domain profile. Another, more distant human homolog, TRAM, which lacks this motif, did not complement. LAG1Hs also restored the life span of the double deletion, demonstrating that it functions in establishing the longevity phenotype in yeast. LAG1Hs mapped to 19p12, and it was expressed in only three tissues: brain, skeletal muscle, and testis. This gene possesses a trinucleotide (CTG) repeat within exon 1. This and its expression profile raise the possibility that it may be involved in neurodegenerative disease. This possibility suggests at least one way in which LAG1Hs might be involved in human aging.

Aging↗