Journal ArticleDOI
Invertebrate gerontology: the age mutations of Caenorhabditis elegans.
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TLDR
Rather than invertebrate ageing being determined by a ‘clock mechanism’, a picture is emerging of ageing as a non‐adaptive process determined, in part, by resistance to intrinsic stress mediated by stress‐response genes.Abstract:
Ageing is a complex phenomenon which remains a major challenge to modern biology. Although the evolutionary biology of ageing is well understood, the mechanisms that limit lifespan are unknown. The isolation and analysis of single-gene mutations which extend lifespan (Age mutations) is likely to reveal processes which influence ageing. Caenorhabditis elegans is the only metazoan in which Age mutations have been identified. The Age mutations not only prolong life, but also confer a complex array of other phenotypes. Some of these phenotypes provide clues to the evolutionary origins of these genes while others allude to mechanisms of lifespan-extension. Many of the Age genes interact and share a second common phenotype, that of stress resistance. Rather than invertebrate ageing being determined by a 'clock mechanism', a picture is emerging of ageing as a non-adaptive process determined, in part, by resistance to intrinsic stress mediated by stress-response genes.read more
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Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology
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Journal ArticleDOI
Genotype-environment interaction for quantitative trait loci affecting life span in Drosophila melanogaster.
Cristina Vieira,Elena G. Pasyukova,Elena G. Pasyukova,Zhao-Bang Zeng,J. B. Hackett,Richard F. Lyman,Trudy F. C. Mackay +6 more
TL;DR: The nature of genetic variation for Drosophila longevity in a population of recombinant inbred lines was investigated, providing support for the pleiotropy theory of senescence and the hypothesis that variation for longevity might be maintained by opposing selection pressures in males and females and variable environments.
Journal ArticleDOI
Type 5 Adenylyl Cyclase Disruption Increases Longevity and Protects Against Stress
Lin Yan,Dorothy E. Vatner,J. Patrick O'Connor,Andreas S. Ivessa,Hui Ge,Wei Chen,Shinichi Hirotani,Yoshihiro Ishikawa,Junichi Sadoshima,Stephen F. Vatner +9 more
TL;DR: A significant activation of the Raf/MEK/ERK signaling pathway and upregulation of cell protective molecules, including superoxide dismutase are demonstrated and suggest that AC is a fundamentally important mechanism regulating lifespan and stress resistance.
References
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Journal Article
Genetic Analysis of Life-Span in Caenorhabditis elegans
Abstract: Crosses between Bristol and Bergerac strains of the self-fertilizing hermaphroditic nematode Caenorhabditis elegans do not show the heterosis effects for life-span that complicate analysis of interstrain crosses with Drosophila or mice. Instead they yield F1 progeny with life-spans similar to those of the parent strains. By analysis of life-span variation among progeny F2 populations from such crosses and by two independent analyses of lifespans among recombinant inbred lines derived from F2 individuals by 18 rounds of self-fertilization, we estimate that the heritability of life-span in C. elegans is between 20% and 50%. Recombinant inbred lines show a range in mean life-spans of 10 days to 31 days compared to life-spans of about 18 days for each of the two parental strains. We conclude that life-span variation in C. elegans has a substantial genetic component and that this organism offers promising opportunities for selective breeding of longer-lived strains and genetic analysis of senescence. The extent to which genes determine life-span in animals remains controversial. For example, two recent studies suggest little or no genetic control of life-span in the Oregon R strain of Drosophila (1, 2). In contrast, another investigation led to estimates as high as 79% for heritability of life-span in mice (3). Direct genetic analysis of this question has been prevented so far by failure to identify specific life-span mutants. At the same time, selective breeding for naturally occurring life-span differences between laboratory strains of common experimental organisms has been hampered by heterosis effects: that is, the hybrid progeny from interstrain crosses live significantly longer than does either parent (3-5). An accepted explanation for the heterosis effects seen, for example, with Drosophila and mice is that being inbred, laboratory strains have become homozygous for recessive alleles that shorten life-span but are not selected against under laboratory conditions. Interbreeding of these strains restores heterozygosity in the F1 progeny, resulting in increased life-span. In hermaphroditic species that are predominantly or solely inbred, such as some snails (6) and nematodes (7), wild animals that are already homozygous at most or all loci might be expected to have evolved optimal life-spans. Therefore, maintenance of small laboratory populations should not markedly shorten life-span by inbreeding, and crosses between laboratory strains should show little or no heterosis effect. In this study we developed methods that improve the reproducibility of life-span determination in Caenorhabditis elegans. Using these methods we have demonstrated that no heterosis effects are observed in crosses between two strains, var. Bristol and var. Bergerac, which have been maintained as laboratory stocks since the 1940s. This characteristic simplifies estimation of life-span heritability, the component of life-span variation that is due to genetic rather than environmental facThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. ? 1734 solely to indicate this fact. tors. We have made heritability estimates from analysis of the increased variation in life-span among progeny F2 populations from interstrain crosses and from two separate analyses of lifespan in recombinant inbred (RI) lines derived from F2 individuals by repeated self-fertilization. The three analyses suggest that heritability of life-span is between 20% and 50%. The RI lines from these crosses include longer-lived strains that may be useful for further, more direct, genetic analysis of aging. MATERIALS AND METHODS Strains, Media, and General Techniques. Stocks of C. elegans were maintained at 20?C as described by Brenner (7) unless otherwise indicated. Wild-type strains included the N2 strain of var. Bristol (N7) and var. Bergerac (8) obtained from D. Hirsh. Escherichia coli strains used as food sources for C. elegans were OP50 (for growth on NGM agar plates) and B/r (for growth in liquid culture). Male and hermaphrodite master stocks were maintained for up to 8 months as dauerlarvae (9) on NGM plates sealed with Parafilm and kept at 16?C. Establishment of Survival Populations. Dauerlarvae were allowed to mature and reproduce for one generation on NGM agar plates, and at the fourth larval stage their F1 progeny were transferred to fresh NGM plates. Two days later these adult worms were used to start synchronous aging populations by transfer of appropriate parents (hermaphrodites and males for crosses; hermaphrodites alone for selfing) to fresh NGM plates preseeded with E. coli OP50. After 4-12 hr of egg laying, the adults were removed, and the synchronized F2 progeny were allowed to mature. This procedure was designed to eliminate possible effects of differences in parental age on progeny lifespan. After 3 days, F2 progeny in groups of 50 worms were suspended in S basal medium plus cholesterol (7) and transferred to Falcon plastic Petri plates containing 4 ml of the same medium with 109 E. coli B/r or OP50 per ml. Maintenance temperature and bacterial concentration were chosen to optimize fecundity (10). These survival populations were transferred daily for 5 successive days, by which time almost all worms are past reproductive age. Thereafter, populations were transferred thrice weekly until all worms had died. Criteria of Death. At each transfer of survival populations, the numbers of worms alive, dead, or lost were recorded. Criteria of death were: (a) lack of spontaneous movement, (b) no response when touched with a probe, (c) visible tissue degeneration, and (d) lack of osmotic turgor. Osmotic turgor was assayed by cutting worms that showed criteria a through C; cut living worms extrude body contents as a result of turgor pressure. The "lost" category included worms killed erroneously in checking for turgor pressure or unintentionally as a result of poor technique, worms killed by premature hatching of eggs Abbreviation: RI, recombinant inbred. t Current address: Dept. of Molecular Biology and Biochemistry, University of California, Irvine, CA 92717.
Journal ArticleDOI
Three mutants that extend both mean and maximum life span of the nematode, Caenorhabditis elegans, define the age-1 gene.
TL;DR: In this article, the authors studied four mutants in the nematode Caenorhabditis elegans (MK31, MK542, MK546) and found that they are allelic.
Journal Article
Three Mutants That Extend Both Mean and Maximum Life Span of the Nematode, Caenorhabditis elegans, Define the age-1 Gene
TL;DR: Three of four mutant strains studied in the nematode Caenorhabditis elegans contain recessive mutations that significantly lengthen life; MK542 and MK546 consistently fail to complement the long life phenotype of age-1 and are therefore allelic.
Journal ArticleDOI
A pheromone-induced developmental switch in Caenorhabditis elegans: Temperature-sensitive mutants reveal a wild-type temperature-dependent process.
James W. Golden,Donald L Riddle +1 more
TL;DR: Temperature-sensitive (ts) dauer-constitutive mutants form dauer larvae at a restrictive temperature regardless of environmental stimuli, and mutations appear to indirectly result in a ts phenotype by enhancing the expression of a wild-type ts developmental process.
Journal ArticleDOI
Thermotolerance of a long-lived mutant of Caenorhabditis elegans.
TL;DR: It is proposed that the enhanced ability of Age strains to cope with environmental stress may be mechanistically related to their lower age-specific mortality rates.