Genetic suppression of cryoprotectant toxicity.

We report here a new, unbiased forward genetic method that uses transposon-mediated mutagenesis to enable the identification of mutations that confer cryoprotectant toxicity resistance (CTR). Our method is to select for resistance to the toxic effects of M22, a much-studied whole-organ vitrification solution. We report finding and characterizing six mutants that are resistant to M22.

Movement decline across lifespan of Caenorhabditis elegans mutants in the insulin/insulin-like signaling pathway.

Research in aging biology has identified several pathways that are molecularly conserved across species that extend lifespan when mutated. The insulin/insulin-like signaling (IIS) pathway is one of the most widely studied of these. It has been assumed that extending lifespan also extends healthspan (the period of life with minimal functional loss).

Dietary restriction in C. elegans: recent advances.

The nematode Caenorhabditis elegans continues to serve as a useful model of life extension caused by dietary restriction. Using this model, downstream effectors of dietary restriction-induced longevity have been elucidated, including neuropeptides and cell-surface receptors. Although it remains possible that different forms of dietary restriction may utilize both specific and overlapping mechanisms to promote longevity, the nematode model has revealed roles for autophagy, metabolic energy-sensing and the hypoxic response.

Predicting longevity in C. elegans: fertility, mobility and gene expression.

Expression level of an hsp-16.2::gfp transgene is a predictor of longevity in Caenorhabditis elegans. Here we examine fertility, movement and longevity, comparing high-expressing ("bright") and low-expressing ("dim") animals.

Expression of a single-copy hsp-16.2 reporter predicts life span.

The level of green fluorescent protein expression from an hsp-16.2-based transcriptional reporter predicts life span and thermotolerance in Caenorhabditis elegans. The initial report used a high-copy number reporter integrated into chromosome IV.

Genetic dissection of late-life fertility in Caenorhabditis elegans.

The large post-reproductive life span reported for the free-living hermaphroditic nematode, Caenorhabditis elegans, which lives for about 10 days after its 5-day period of self-reproduction, seems at odds with evolutionary theory. Species with long post-reproductive life spans such as mammals are sometimes explained by a need for parental care or transfer of information. This does not seem a suitable explanation for C elegans.

Quantifying phenotypic variation in isogenic Caenorhabditis elegans expressing Phsp-16.2::gfp by clustering 2D expression patterns.

Isogenic populations of animals still show a surprisingly large amount of phenotypic variation between individuals. Using a GFP reporter that has been shown to predict longevity and resistance to stress in isogenic populations of the nematode Caenorhabditis elegans, we examined residual variation in expression of this GFP reporter. We found that when we separated the populations into brightest 3% and dimmest 3% we also saw variation in relative expression patterns that distinguished the bright and dim worms.

Mortality shifts in Caenorhabditis elegans: remembrance of conditions past.

The analysis of age-specific mortality can yield insights into how anti-aging interventions operate that cannot be matched by simple assessment of longevity. Mortality, as opposed to longevity, can be used to assess the effects of an anti-aging intervention on a daily basis, rather than only after most animals have died. Various gerontogene mutations in Caenorhabditis elegans have been shown to increase longevity as much as tenfold and to decrease mortality at some ages even more.

Multiple mild heat-shocks decrease the Gompertz component of mortality in Caenorhabditis elegans.

Exposure to mild heat-stress (heat-shock) can significantly increase the life expectancy of the nematode Caenorhabditis elegans. A single heat-shock early in life extends longevity by 20% or more and affects life-long mortality by decreasing initial mortality only; the rate of increase in subsequent mortality (Gompertz component) is unchanged. Repeated mild heat-shocks throughout life have a larger effect on life span than does a single heat-shock early in life.

Coenzyme Q supports distinct developmental processes in Caenorhabditis elegans.

Coenzyme Q (Q) regulates aging in Caenorhabditis elegans, and its deficiency leads to a variety of pathologies in humans. We used a coq-8 deleted strain to study the role of Q in C. elegans development and how it influences life span.

The U-shaped response of initial mortality in Caenorhabditis elegans to mild heat shock: does it explain recent trends in human mortality?

U-shaped dose-response relationships (hormesis) have been documented in numerous biological, toxicological, and pharmacological investigations. For example, in response to a mild 35 degrees C heat shock, the longevity of Caenorhabditis elegans exhibits an inverted U-shaped dose-response. By applying the demographic concept of heterogeneity, we find that this U-shaped curve for longevity response is driven by a U-shaped dose-response of initial mortality.

Hormesis and aging in Caenorhabditis elegans.

Hormesis has emerged as an important manipulation for the study of aging. Although hormesis is manifested in manifold combinations of stress and model organism, the mechanisms of hormesis are only partly understood. The increased stress resistance and extended survival caused by hormesis can be manipulated to further our understanding of the roles of intrinsic and induced stress resistance in aging.

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

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.

Insulin regulation of heart function in aging fruit flies.

Insulin-IGF receptor (InR) signaling has a conserved role in regulating lifespan, but little is known about the genetic control of declining organ function. Here, we describe progressive changes of heart function in aging fruit flies: from one to seven weeks of a fly's age, the resting heart rate decreases and the rate of stress-induced heart failure increases. These age-related changes are minimized or absent in long-lived flies when systemic levels of insulin-like peptides are reduced and by mutations of the only receptor, InR, or its substrate, chico.

Hormesis in Caenorhabditis elegans dauer-defective mutants.

We have shown that increased longevity and stress resistance can be induced by sub-lethal exposure to stressors (hormesis). Here we ask whether genes of the dauer formation pathway that are known to modulate life span in Caenorhabditis elegans are required for this hormesis. We find that loss-of-function mutations in any of three genes (daf-16, daf-18, or daf-12) not only reduce or abolish the ability to form dauers but also block the hormetic response increasing life span following sub-lethal heat stress.

Meeting report--44th Annual Drosophila Research Conference.

The ability to compare the genetics of aging in multiple model organisms is a powerful tool to dissect the biology of aging. Although the fruit fly has only about half again as many genes as the nematode worm, its tissue organization is much more complex. The emerging importance of tissue specificity and endocrine signaling in aging makes the fly a natural choice for many researchers interested in unraveling the next level of complexity of the aging process.

Ginkgo biloba extract EGb 761 increases stress resistance and extends life span of Caenorhabditis elegans.

EGb 761, a standardized extract of Ginkgo biloba leaves, has been used in clinical trials for its beneficial effects on brain functions. In mammals, EGb 761 has been shown to enhance cognition, stress resistance, and longevity, but its molecular and cellular mechanisms are not known. In the present investigation, we used the model organism Caenorhabditis elegans to evaluate pharmacological effects of EGb 761 on aging.

Longevity genes in the nematode Caenorhabditis elegans also mediate increased resistance to stress and prevent disease.

More than 40 single-gene mutants in Caenorhabditis elegans have been demonstrated to lead to increased lifespan (a rigorous, operational test for being a gerontogene) of 20% or more; these are referred to collectively as 'Age' mutants. Age mutants must change key functions that are rate-limiting determinants of longevity; moreover, important genes can be identified independently of prior hypotheses as to actual mode of gene action in extending longevity and/or 'slowing' of ageing. These Age mutants define as many as nine (possibly) distinct pathways and/or modes of action, as defined by primary phenotype.

Multiple stressors in Caenorhabditis elegans induce stress hormesis and extended longevity.

We demonstrate here that the nematode Caenorhabditis elegans displays broad hormetic abilities. Hormesis is the induction of beneficial effects by exposure to low doses of otherwise harmful chemical or physical agents. Heat as well as pretreatment with hyperbaric oxygen or juglone (a chemical that generates reactive oxygen species) significantly increased subsequent resistance to the same challenge.

Heat shock changes the heterogeneity distribution in populations of Caenorhabditis elegans: does it tell us anything about the biological mechanism of stress response?

In this paper we analyze survival data of populations of sterilized nematodes, Caenorhabditis elegans, exposed to heat shocks of different duration at the beginning of their adult lives. There are clear hormesis effects after short exposure to heat and clear debilitation effects after long exposure. Intermediate durations result in a mixture of these two effects.

Hormesis and debilitation effects in stress experiments using the nematode worm Caenorhabditis elegans: the model of balance between cell damage and HSP levels.

In this article, we discuss mechanisms responsible for the effects of heat treatment on increasing subsequent survival in the nematode worm Caenorhabditis elegans. We assume that the balance between damage associated with exposure to thermal stress and the level of heat shock proteins produced plays a key role in forming the age-pattern of mortality and survival in stress experiments. We propose a stochastic model of stress, which describes the accumulation of damage in the cells of the worm as the worm ages.

Heating stress patterns in Caenorhabditis elegans longevity and survivorship.

Survival data from Caenorhabditis elegans strain TJ1060 (spe-9; fer-15) following brief exposure to 35 degrees C have been investigated. Three experiments with 3-day-old worms were conducted with heat duration ranging between 0 and 12 hours. A statistically significant increase in life expectancy was observed in the groups heated for less than 2 hours, as compared to the unheated control groups.

Relationship between increased longevity and stress resistance as assessed through gerontogene mutations in Caenorhabditis elegans.

We review the status of the hypothesis that interventions that increase the resistance to stress offer the potential for effective life prolongation and increased health. The work focuses on research in the nematode worm Caenorhabditis elegans and describes both published and unpublished results consistent with this hypothesis. Correlation between stress resistance and longevity among many gerontogene mutants is provided.

Ageing and survival after different doses of heat shock: the results of analysis of data from stress experiments with the nematode worm Caenorhabditis elegans.

Stress experiments performed on a population of sterilised nematode worms (Caenorhabditis elegans) show a clear hormesis effect after short exposure and clear debilitation effects after long exposure to heat shock. An intermediate duration of exposure results in a mixture of these two effects. In this latter case the survival curves for populations in the stress and control groups intersect.