Properties of ethylmethane sulfonate-induced mutations affecting life-history traits in Caenorhabditis elegans and inferences about bivariate distributions of mutation effects.
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The homozygous effects of ethylmethane sulfonate (EMS)-induced mutations in Caenorhabditis elegans are compared across life-history traits. Mutagenesis has a greater effect on early than late reproductive output, since EMS-induced mutations tend to cause delayed reproduction. Mutagenesis changes the mean and variance of longevity much less than reproductive output traits. Mutations that increase total or early productivity are not detected, but the net effect of mutations is to increase and decrease late productivity to approximately equal extents. Although most mutations decrease longevity, a mutant line with increased longevity was found. A flattening of mortality curves with age is noted, particularly in EMS lines. We infer that less than one-tenth of mutations that have fitness effects in natural conditions are detected in the laboratory, and such mutations have moderately large effects ( approximately 20% of the mean). Mutational correlations for life-history traits are strong and positive. Correlations between early or late productivity and longevity are of similar magnitude. We develop a maximum-likelihood procedure to infer bivariate distributions of mutation effects. We show that strong mutation-induced genetic correlations do not necessarily imply strong directional correlations between mutational effects, since correlation is also generated by lines carrying different numbers of mutations. (+info)
Rearing of Lymnaea columella (Say, 1817), intermediate host of Fasciola hepatica (Linnaeus, 1758).
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The intermediate host of Fasciola hepatica, Lymnaea columella, collected in Belo Horizonte, Minas Gerais, Brazil, was reared in our laboratory. The aim of the current study was to standardize a rearing and maintenance technique. Two kinds of diet were tested: fresh lettuce (A) and rodent ration + 10% CaCO3 plus fresh lettuce (B). The age for the beginning of oviposition ranged from 27 to 57 days. Ten days after oviposition at 24.7 degrees C, 100% eclosion occurred. The complete life cycle varied from 37 to 67 days. The average numbers of eggs per egg mass were 26.3 and 31.1 with diets (A) and (B), respectively. The lettuce and ration fed snails presented a increased growth although the difference was not statistically significant (p > 0.05). The mortality rate varied from 40 to 64% after 90 days. The maximum longevity was 183 days, 21.5 mm length and 11 mm wide. The methodology to mass breed and maintain these snails was found to be suitable in the laboratory (+info)
Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae.
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Calorie restriction extends life-span in a wide variety of organisms. Although it has been suggested that calorie restriction may work by reducing the levels of reactive oxygen species produced during respiration, the mechanism by which this regimen slows aging is uncertain. Here, we mimicked calorie restriction in yeast by physiological or genetic means and showed a substantial extension in life-span. This extension was not observed in strains mutant for SIR2 (which encodes the silencing protein Sir2p) or NPT1 (a gene in a pathway in the synthesis of NAD, the oxidized form of nicotinamide adenine dinucleotide). These findings suggest that the increased longevity induced by calorie restriction requires the activation of Sir2p by NAD. (+info)
Increase of maximum life-span in Sweden, 1861-1999.
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A fundamental question in aging research is whether humans and other species possess an immutable life-span limit. We examined the maximum age at death in Sweden, which rose from about 101 years during the 1860s to about 108 years during the 1990s. The pace of increase was 0.44 years per decade before 1969 but accelerated to 1. 11 years per decade after that date. More than 70 percent of the rise in the maximum age at death from 1861 to 1999 is attributable to reductions in death rates above age 70. The rest are due to increased numbers of survivors to old age (both larger birth cohorts and increased survivorship from infancy to age 70). The more rapid rise in the maximum age since 1969 is due to the faster pace of old-age mortality decline during recent decades. (+info)
Regulation of C. elegans life-span by insulinlike signaling in the nervous system.
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An insulinlike signaling pathway controls Caenorhabditis elegans aging, metabolism, and development. Mutations in the daf-2 insulin receptor-like gene or the downstream age-1 phosphoinositide 3-kinase gene extend adult life-span by two- to threefold. To identify tissues where this pathway regulates aging and metabolism, we restored daf-2 pathway signaling to only neurons, muscle, or intestine. Insulinlike signaling in neurons alone was sufficient to specify wild-type life-span, but muscle or intestinal signaling was not. However, restoring daf-2 pathway signaling to muscle rescued metabolic defects, thus decoupling regulation of life-span and metabolism. These findings point to the nervous system as a central regulator of animal longevity. (+info)
Inheritance of human longevity in Iceland.
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The idea that human longevity is influenced by genetic factors has recently received strong support from work on other species. On the basis of partial population studies and selected kinships, significant correlations between the ages of parents and offspring have been reported, and some but not all twin studies have confirmed that human longevity is moderately inherited. However, studies based upon a relatively small proportion of a population are susceptible to sampling error and selection bias. Here we report the use of a comprehensive population-based computerised genealogy database to examine multigenerational relationships among those who live to the 95th percentile in Iceland. We have developed a clustering tool which can generate large extended pedigrees connecting individuals from any list using the genealogy database. First degree relatives of those living to the 95th percentile are almost twice as likely to live to the 95th percentile compared with controls. Furthermore, we have developed an algorithm which we have named the Minimum Founder Test (MFT) to examine the degree of relatedness of any population-based list of individuals to estimate whether a trait has a familial component. The data indicate that there is a significant genetic component to longevity. In addition, age-specific death rates are significantly lower in the offspring of long-lived parents compared with controls, especially after age 70. (+info)
Aging and longevity genes.
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The genetics of aging has made substantial strides in the past decade. This progress has been confined primarily to model organisms, such as filamentous fungi, yeast, nematodes, fruit flies, and mice, in which some thirty-five genes that determine life span have been cloned. These genes encode a wide array of cellular functions, indicating that there must be multiple mechanisms of aging. Nevertheless, some generalizations are already beginning to emerge. It is now clear that there are at least four broad physiological processes that play a role in aging: metabolic control, resistance to stress, gene dysregulation, and genetic stability. The first two of these at least are common themes that connect aging in yeast, nematodes, and fruit flies, and this convergence extends to caloric restriction, which postpones senescence and increases life span in rodents. Many of the human homologs of the longevity genes found in model organisms have been identified. This will lead to their use as candidate human longevity genes in population genetic studies. The urgency for such studies is great: The population is graying, and this research holds the promise of improvement in the quality of the later years of life. (+info)
The effects of diet, ad Libitum feeding, and moderate and severe dietary restriction on body weight, survival, clinical pathology parameters, and cause of death in control Sprague-Dawley rats.
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A 2-year study was conducted in Sprague-Dawley rats to compare the effects of ad libitum (AL) feeding and dietary restriction (DR) on body weight, survival, cause of death, and clinical pathology parameters. Three groups of 120 rats/sex each received the following daily rations of a maintenance rodent diet: ad libitum (AL group); 75% of adult AL food consumption (25% DR group); and 45% of adult AL food consumption (55% DR group). Among the 3 groups, there were generally no differences in relative (food intake per gram of body weight) food consumption. Compared to the AL group, decreased body weight gain occurred in DR groups and was associated with an increase in survival proportional to the DR rate. The main cause of death was pituitary adenomas in all groups. Decreases in total leukocyte, segmented neutrophil, lymphocyte, and platelet counts occurred in the 55% DR group. In serum biochemistry, there were decreases in total protein, albumin, total and HDL cholesterol, and total calcium, and increases in alkaline phosphatase activities and chloride in 55% DR females, as well as decreases in triglycerides in the 55% DR group and in 25% DR females. Results of urinalyses showed decreases in urine volume and protein, and increases in urinary pH in both DR groups. In conclusion, a DR rate of approximately 25% appears to be appropriate for Sprague-Dawley rats in toxicity and carcinogenicity assays to improve survival without impairing growth and routine clinical pathology parameters. (+info)