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PubMed2000

Is there a trade-off between longevity and quality of life in Grossman's pure investment model?

The question is posed whether an individual maximizes lifetime or trades off longevity for quality of life in Grossman's pure investment (PI)-model. It is shown that the answer critically hinges on the assumed production function for healthy time. If the production function for healthy time produces a trade-off between life-span and quality of life, one has to solve a sequence of fixed time problems. The one offering maximal intertemporal utility determines optimal longevity. Comparative static results of optimal longevity for a simplified version of the PI-model are derived. The obtained results predict that higher initial endowments of wealth and health, a rise in the wage rate, or improvements in the technology of producing healthy time, all increase the optimal length of life. On the other hand, optimal longevity is decreasing in the depreciation and interest rate. From a technical point of view, the paper illustrates that a discrete time equivalent to the transversality condition for optimal longevity employed in continuous optimal control models does not exist.

Algorithms↗
PubMed1991

Elevated paraquat resistance can be used as a bioassay for longevity in a genetically based long-lived strain of Drosophila.

A long-lived (L) strain of Drosophila melanogaster, derived from a normal-lived (R) strain by artificial selection, has a significantly different adult longevity. Previous work has shown that 1) the two strains age in the same manner, 2) the major genes responsible for much of the L strain's extended longevity are located on the 3rd chromosome, and 3) the extended longevity phenotype is significantly modulated by the larval environment. In this report, we investigate the resistance of the L and R strains to the lethal effects of dietary paraquat. We show that, within the limitations of our described chromosomal and environmental manipulations, the extended longevity phenotype always accompanies the phenotype of elevated paraquat resistance. In addition, reversed selection applied to the L strain results in the simultaneous decrease of both life span and paraquat resistance. Thus, the presence or absence of the latter phenotype may be used as a bioassay for the presence or absence of the extended longevity phenotype, without any necessary implication of causality. Use of this bioassay should greatly speed up the genetic analysis of this system by allowing us to identify long-lived animals at a young age. Finally, we show that the age-related loss of elevated paraquat resistance in both strains precedes all the other age-related functional decrements which we have previously noted in this system.

Animals↗
PubMed2002

Metabolic aging and predicted longevity: results of a cross-sectional study in post-menopausal women.

BACKGROUND AND AIMS: The extent to which general characteristics of metabolic aging contribute to differences in life span among individuals remains uncertain. The objective of this study was to examine the association of age-related physiological and metabolic variables with predicted longevity in postmenopausal women. METHODS: Subjects were 33 healthy women aged 55-65 years. Total and resting energy expenditure, body temperature, immune function as assessed by a delayed-type hypersensitivity skin test (DTH), lipid profile, and reported dietary intake were measured. RESULTS: There were no significant associations between longevity, energy expenditure, body temperature, lipid profile, or dietary intake. However, there was a significant association of predicted longevity with DTH (partial r=0.44, p=0.023). CONCLUSIONS: These results suggest that immune function may predict familial differences in longevity, while energy expenditure, body temperature, lipid profile, and dietary intake are unrelated. Although the small sample size may have limited the ability to detect metabolic effects on longevity in this study, the general approach may be broadly applicable to examinations of metabolic aging in humans.

Aged↗
PubMed1982

Influence of preimaginal constant and alternating temperatures on growth rate and longevity of adults of five genotypes in Tribolium castaneum.

The longevity of adults of five genotypes of Tribolium castaneum differing in their body weights was measured at a single constant temperature, 35 degrees C, after they had developed at three constant temperatures, 25, 30 or 35 degrees C, and one alternating temperature 25/35 degrees C (mean = 30 degree C). Two genotypes had been naturally selected for heavy and light body weights, two had been artificially selected for extreme pupal weights and one was the pygmy mutant. The main results are as follows. (1) There is a negative correlation between growth rate and imaginal longevity for four of the five genotypes, when the variations in growth rate are due to the influence of constant developmental temperatures. (2) The genotype has a marked effect on mean longevity and on the slope of the regression of longevity on growth rate. (3) Growth rate is larger and longevity is longer when the larvae are raised at alternating 25/35 degrees C than when they are raised at a constant 30 degrees C. These results seem to confirm the developmental theory of ageing.

Animals↗
PubMedDate not supplied

Hypergravity and aging in Drosophila melanogaster: 7. New longevity data.

Longevity of mated and virgin Drosophila melanogaster flies was observed at various gravity levels (1-7.38 g). A slight longevity decrease was observed in the 1-5.14 g range for virgin males, and a larger one in the 5.14-7.38 g range. The effect of gravity was larger for females in the 1-5.14 g range, and at the highest gravity level, both sexes had roughly the same longevity, which however remained high (around 40 days). The longevity of mated flies was lower than that of virgins at 1 g, and only a slight longevity decrease was observed in the 1-7.38 g range in females, this decrease being larger for males. Hypergravity appears to have no dramatic effects on life span and to be of lower importance than the simple effect of mating. This study confirms previous results obtained in the 1-5.02 g range with virgin flies (Le Bourg and Lints, 1989).

Animals↗
PubMed2005

Influence of caste polyethism on longevity of workers in social insect colonies.

Different patterns of division of labor can affect the expected longevity of social insects workers. It has been earlier suggested that when tasks performed inside and outside colony are equally risky then the expected longevity of workers in colonies with caste polyethism is greater than that in colonies without polyethism. To verify these predictions I used a model assuming two sets of tasks, associated with different mortality rates. In the colony without polyethism the workers preformed safe and risky tasks in turn, while in the colony with caste polyethism the workers specialized in only one set of tasks. The outcomes suggest that the expected longevity of workers in colonies with caste polyethism cannot be greater than that in colonies without polyethism. Only if there is no aging and under some special and rare conditions are there no differences in expected longevity between colonies with and without caste polyethism. If aging is independent of activity, caste polyethism does not shorten longevity when all tasks in the colony are equally risky. The results can explain why caste polyethism is not as widespread among social insects as age polyethism.

Animals↗
PubMed2005

p66ShcA and ageing: modulation by longevity-promoting agent aurintricarboxylic acid.

Many mutations that extend the lifespan of the lower organisms such as C. elegans and Drosophila, are associated with signaling or apoptotic pathways. Recently, such a possibility was shown in mammals: p66ShcA-deficient mice were more resistant to oxidative stress and lived longer than the wild-type animals [Migliaccio, E., Giorgio, M., Mele, S., Pelicci, G., Reboldi, P., Randolfi, P.P., Lanfrancone, L., Pelicci, P.G., 1999. The p66Shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402, 309-313]. There is evidence to implicate p66ShcA in age-related degenerative pathology, including atherosclerosis, sarcopenia, and Alzheimer's disease. We hypothesized that a low level expression of p66ShcA could be associated with longevity. Also, we suggested that the level of p66ShcA could be modulated by a putative longevity-promoting agent aurintricarboxylic acid [aurintricarboxylic acid (ATA); Fraifeld, V., Wolfson, M., Sagi, O., Seidman, R., Asraf, H., Utko, N., Muradian, K., 2002. Effects of anti-apoptotic agent aurintricarboxylic acid on longevity and longevity-associated processes. Biogerontology 3, 48]. We have found that: (i) the level of p66ShcA decreases with advanced age. Thirty-six-month-old mice have the lowest, whereas newborns have the highest p66ShcA levels; (ii) ATA significantly decreases the p66ShcA level in mouse lungs. In addition, the lifespan-prolongation effect of ATA in a Drosophila model was further validated. The results support the suggested role for the p66ShcA as one of the lifespan determinants in mammals; p66ShcA therefore represents a potential target for pharmacological longevity-promoting intervention.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Biological evidence for inheritance of exceptional longevity.

Subjects with exceptional longevity have a lower incidence and/or significant delay in the onset of age-related disease, and their family members may inherit biological factors that modulate aging processes and disease susceptibility. In a case control study, we aim to determine phenotype and genotype of exceptional longevity in a genetically homogenous population (Ashkenazi Jews), and their offspring, while an age-matched control group of Ashkenazi Jews was used as control groups. We demonstrated that exceptional longevity and healthy aging in humans is an inherited phenotype across three generations. Moreover, we demonstrated that subjects with exceptional longevity and their offspring have significantly larger high-density lipoprotein (HDL) levels and particle sizes and low-density lipoprotein (LDL) levels that reflect on their health and cognitive function performance. This phenotype have led us to study candidate genes involved in lipoprotein metabolism, and to the implication of homozygosity for the 405 valine (V) allele of cholesteryl ester transfer protein (CETP). A markedly higher frequency of a functional CETP variant that led to increased particle sizes of HDL and LDL and thus a better health performance is the first example of a phenotype and an associated genotype in humans with exceptional longevity. Hopefully, this line of research will lead us to establish which genotype is necessary (although not necessary sufficient) for a prolonged disease-free aging.

Age Factors↗
PubMed2004

Hypothesis on transmission of longevity based on telomere length and state of integrity.

Different studies have demonstrated that offspring longevity depends on parental longevity and parental age at conception. The present paper suggests, based on the telomere theory of aging, that the longevity of the offspring is proportional to the telomere length and inversely proportional to the telomere state of integrity in the sperm cell and oocyte at conception. These two characteristics of telomeres depend on the age of parents. Telomeres become longer in gametes during the course of life, but at the same time they accumulate mutations (reduced state of integrity) that cause a faster loss of repetitive sequences. Because of these two mechanisms with opposing effects, there could exist an ideal age of the parents for the transmission of maximal longevity. The different longevity of men and women could partly be the result of different telomere dynamics of the sex chromosomes. The hypothesis also explains the risk of some birth defects associated with parental age at birth (telomeres are taken as a cause of birth defects).

Aging↗
PubMed2002

The nature of quantitative genetic variation for Drosophila longevity.

Longevity is a typical quantitative trait: the continuous variation in life span observed in natural populations is attributable to genetic variation at multiple quantitative trait loci (QTL), environmental sensitivity of QTL alleles, and truly continuous environmental variation. To begin to understand the genetic architecture of longevity at the level of individual QTL, we have mapped QTL for Drosophila life span that segregate between two inbred strains that were not selected for longevity. A mapping population of 98 recombinant inbred lines (RIL) was derived from these strains, and life span of virgin male and female flies measured under control culture conditions, chronic heat and cold stress, heat shock and starvation stress, and high and low density larval environments. The genotypes of the RIL were determined for polymorphic roo transposable element insertion sites, and life span QTL were mapped using composite interval mapping methods. A minimum of 19 life span QTL were detected by recombination mapping. The life span QTL exhibited strong genotype by sex, genotype by environment, and genotype by genotype (epistatic) interactions. These interactions complicate mapping efforts, but evolutionary theory predicts such properties of segregating QTL alleles. Quantitative deficiency mapping of four longevity QTL detected in the control environment by recombination mapping revealed a minimum of 11 QTL in these regions. Clearly, longevity is a complex quantitative trait. In the future, linkage disequilibrium mapping can be used to determine which candidate genes in a QTL region correspond to the genetic loci affecting variation in life span, and define the QTL alleles at the molecular level.

Animals↗
PubMed1997

HLA and longevity or aging among Shanghai Chinese.

Twenty-two centenarians and one hundred and seventy-nine nonagenarians (mean age 93 +/- 1.04 years) in the Shanghai Region of China were phenotyped for alleles of A (13 types), B (21 types) and C (6 types) loci of the human leukocyte antigen (HLA). The frequencies of HLA antigens were compared with 211 healthy adults whose ages ranged from 20 to 50 years. It was observed that A9 was highly associated with longevity (frequency in the longevity group is 38%, the control group 24%, P = 0.002). A30 showed marked inverse correlation (frequency in the longevity group is 8%, the control group 17%, P = 0.008). Cw3, Cw6 and Cw7 were also inversely correlated (P = 0.02, 0.04 and 0.02, respectively). Thus, it is likely that A9 may contribute to longevity while A30, Cw3, Cw6 and Cw7 may be associated with aging. The average superoxide dismutase (SOD) contents of erythrocytes in 48 cases with the HLA-A9 (without A30) antigen in the longevity group and in 13 cases with the HLA-A30 (without A9) antigen in the control group were 555 +/- 96 and 593 +/- 58 micrograms/gHb, respectively (t = 1.375, P > 0.05).

Adult↗
PubMed2000

Gerontogenes mediate health and longevity in nematodes through increasing resistance to environmental toxins and stressors.

More than 40 mutants in Caenorhabditis elegans have been demonstrated to lead to increased life span (a rigorous, operational test for being a gerontogene) of 20% or more ("Age" mutants). Age mutants alter rate-limiting determinants of longevity; moreover, important genes are identified independent of prior hypotheses as to actual mode of gene action in extending longevity and/or "slowing" aging. Age mutants define as many as nine (possibly) distinct pathways and/or modes of action, as defined by primary phenotype. Three well-studied mutants (age-1, clk-1, and spe-26) alter age-specific mortality rates in characteristic fashions; in age-1 mutants, especially, the changes in mortality rates are quite dramatic. All Age mutants (so far without exception) increase response to several (but not all) stresses, including heat, UV, and reactive oxidants. We have used directed strategies, as well as random mutagenesis, to identify novel genes increasing the worm's ability to resist stress. Two genes (daf-16 and old-1) yield over-expression strains that are stress resistant and long-lived. A variety of approaches to assess transcriptional alterations associated with increased longevity are underway. We suggest that the role of the Age genes in both longevity and stress resistance indicates that a major evolutionary determinant of longevity is the ability to respond to stress.

Aging↗
PubMed2003

Genome size and longevity in fish.

The wide variety of genome sizes (measured as C-value) observed across taxa is not related to organismal complexity or number of coding genes. Partial answers to this C-value enigma have been found by establishing associations between C-value and particular phenotypic characteristics. One such controversial association has been recently suggested between genome size and longevity in birds. In order to determine whether genome size is a general predictor of longevity, we have extended the analysis to the Actinoptergyian fish, a widely divergent group in terms of both longevity and genome size. We collected data on genome size, longevity and body mass for species covering fourteen orders of bony fish. Analysis of covariance using order as a cofactor shows a significant effect of genome size on longevity (corrected for body mass), with lifespan increasing as a function of genome size. Analysis of phylogenetically independent contrasts for orders with a large number of species with a well resolved phylogenetic relationship (Acipenseriformes, Cypriniformes, and Salmoniformes) found the same trend of longer lifespan with increases in genome size but the relationship was not significant. Our results consistently show an increase in lifespan for fish with larger genomes.

Analysis of Variance↗
PubMed2000

Forward and reverse selection for longevity in Drosophila is characterized by alteration of antioxidant gene expression and oxidative damage patterns.

Patterns of antioxidant gene expression and of oxidative damage were measured throughout the adult life span of a selected long-lived strain (La) of Drosophila melanogaster and compared to that of their normal-lived progenitor strain (Ra). Extended longevity in the La strain is correlated with enhanced antioxidant defense system gene expression, accumulation of CuZnSOD protein, and an increase in ADS enzyme activities. Extended longevity is strongly associated with a significantly increased resistance to oxidative stress. Reverse-selecting this long-lived strain for shortened longevity (RevLa strain) yields a significant decrease in longevity accompanied by reversion to normal levels of its antioxidant defense system gene expression patterns and antioxidant enzyme patterns. The significant effects of forward and reverse selection in these strains seem limited to the ADS enzymes; 11 other enzymes with primarily metabolic functions show no obvious effect of selection on their activity levels whereas six other enzymes postulated to play a role in flux control may actually be involved in NADPH reoxidation and thus support the enhanced activities of the ADS enzymes. Thus, alterations in the longevity of these Drosophila strains are directly correlated with corresponding alterations in; 1) the mRNA levels of certain antioxidant defense system genes; 2) the protein level of at least one antioxidant defense system gene; 3) the activity levels of the corresponding antioxidant defense system enzymes, and 4) the ability of the organism to resist the biological damage arising from oxidative stress.

Acatalasia↗
PubMed2000

A mild stress due to hypergravity exposure at young age increases longevity in Drosophila melanogaster males.

Drosophila melanogaster flies were exposed to hypergravity starting at two days of age, the range of gravity levels used being 2.58-7.38 g. No longevity change was observed for exposures of less than 14 days. The longevity of males increased if they were submitted to hypergravity for durations ranging from 14 to 24 days. This increase in longevity was never observed in females. The positive effect of exposure to hypergravity has been replicated in two laboratories using two wild-type strains and different rearing conditions. A short hypergravity exposure seems to be a mild stress, yielding positive effects on longevity. This is in accordance with two previous studies showing a slight longevity increase after heat shock in the nematode Caenorhabditis elegans and in Drosophila melanogaster.

Animals↗
PubMed2001

Neural-specific overexpression of drosophila plenty of SH3s (DPOSH) extends the longevity of adult flies.

Extended longevity mutants are extremely useful to understand the molecular mechanism of longevity determination. Here we report identification and characterization of the Drosophila Plenty of SH3s (DPOSH) gene, a candidate that might be associated with the extended longevity phenotype. DPOSH encodes a protein containing a RING finger domain and four SH3 domains. We showed that neural-specific overexpression of DPOSH could extend the mean longevity of adult flies by 14% at 25 degrees C without affecting viability or morphology. In contrast, forced expression of DPOSH in developing imaginal discs produced various phenotypes including lethality and morphological defects such as loss of crossvein, notched wing, and disordered hair polarity. Puckered, a target gene of JNK/SAPK pathway, was activated by overexpression of DPOSH and the forced expression phenotypes were suppressed by introducing a mutation of Drosophila JNK (bsk) or JNKK (hep), suggesting that the JNK/SAPK signaling pathway is one of the critical elements in the determination of longevity.

Adaptor Proteins, Signal Transducing↗
PubMed1993

Chromosomal localization and regulation of the longevity determinant genes in a selected strain of Drosophila melanogaster.

A controlled chromosome substitution experiment was performed on a strain (NDC-L) selected for long life to determine if the genes responsible for the extended-longevity phenotype could be localized to any particular chromosome(s). All 27 different possible combinations of the three major chromosomes of Drosophila melanogaster were constructed and longevities were determined on 3875 individual animals of both sexes and analysed. The results are statistically significant and demonstrate that mean longevity is specified primarily by recessive genes on the third chromosome (c3). The extended longevity phenotype (ELP) is only expressed in those lines which are homozygous for the NDC-L type c3. Loci on the first (c1) and second (c2) chromosomes interact, both positively (c1) and negatively (c2), respectively, such that c1 represses c2 which in turn represses c3. The ELP is fully expressed in the mutual presence and mutual absence of c1 and c2. The significance of these results is discussed in the context of broader categories of molecular genetic mechanisms suggested previously to be involved in the modulation of longevity in Drosophila.

Animals↗
PubMed2002

A centenarian-only approach for assessing gene-gene interaction in human longevity.

In this study, we introduce a centenarian-only approach to the assessment of gene-gene interaction that contributes to human longevity. This approach corresponds to the non-traditional case-only method in the genetic study of gene and disease associations. We first describe how the method can be implemented to screen for gene-gene interaction in human longevity. Then we apply the method to centenarian data collected from an Italian centenarian study in order to detect the interactions between the REN gene and the mitochondrial haplotypes. A significant interaction between REN gene allele 10 and the mitochondrial H haplotype, which may favour longevity, was found. Important features of the application in human longevity studies are highlighted and discussed. Since centenarians constitute a special population representing successful ageing, the centenarian-only approach will be an important tool in the search for major genes that contribute to human longevity.

Aged↗