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      A stress-sensitive reporter predicts longevity in isogenic populations of Caenorhabditis elegans.

      Nature genetics
      Animals, Caenorhabditis elegans, genetics, physiology, Caenorhabditis elegans Proteins, Genes, Reporter, Green Fluorescent Proteins, Heat-Shock Proteins, Longevity, Promoter Regions, Genetic, Stress, Physiological

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          Abstract

          When both genotype and environment are held constant, 'chance' variation in the lifespan of individuals in a population is still quite large. Using isogenic populations of the nematode Caenorhabditis elegans, we show that, on the first day of adult life, chance variation in the level of induction of a green fluorescent protein (GFP) reporter coupled to a promoter from the gene hsp-16.2 predicts as much as a fourfold variation in subsequent survival. The same reporter is also a predictor of ability to withstand a subsequent lethal thermal stress. The level of induction of GFP is not heritable, and GFP expression levels in other reporter constructs are not associated with differences in longevity. HSP-16.2 itself is probably not responsible for the observed differences in survival but instead probably reflects a hidden, heterogeneous, but now quantifiable, physiological state that dictates the ability of an organism to deal with the rigors of living.

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          Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans.

          The nematode Caenorhabditis elegans is an important model for studying the genetics of ageing, with over 50 life-extension mutations known so far. However, little is known about the pathobiology of ageing in this species, limiting attempts to connect genotype with senescent phenotype. Using ultrastructural analysis and visualization of specific cell types with green fluorescent protein, we examined cell integrity in different tissues as the animal ages. We report remarkable preservation of the nervous system, even in advanced old age, in contrast to a gradual, progressive deterioration of muscle, resembling human sarcopenia. The age-1(hx546) mutation, which extends lifespan by 60-100%, delayed some, but not all, cellular biomarkers of ageing. Strikingly, we found strong evidence that stochastic as well as genetic factors are significant in C. elegans ageing, with extensive variability both among same-age animals and between cells of the same type within individuals.
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            Control, exploitation and tolerance of intracellular noise.

            Noise has many roles in biological function, including generation of errors in DNA replication leading to mutation and evolution, noise-driven divergence of cell fates, noise-induced amplification of signals, and maintenance of the quantitative individuality of cells. Yet there is order to the behaviour and development of cells. They operate within strict parameters and in many cases this behaviour seems robust, implying that noise is largely filtered by the system. How can we explain the use, rejection and sensitivity to noise that is found in biological systems? An exploration of the sources and consequences of noise calls for the use of stochastic models.
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              Biodemographic trajectories of longevity.

              Old-age survival has increased substantially since 1950. Death rates decelerate with age for insects, worms, and yeast, as well as humans. This evidence of extended postreproductive survival is puzzling. Three biodemographic insights--concerning the correlation of death rates across age, individual differences in survival chances, and induced alterations in age patterns of fertility and mortality--offer clues and suggest research on the failure of complicated systems, on new demographic equations for evolutionary theory, and on fertility-longevity interactions. Nongenetic changes account for increases in human life-spans to date. Explication of these causes and the genetic license for extended survival, as well as discovery of genes and other survival attributes affecting longevity, will lead to even longer lives.
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