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Journal ArticleDOI

Invertebrate gerontology: the age mutations of Caenorhabditis elegans.

Gordon J. Lithgow
- 01 Oct 1996 - 
- Vol. 18, Iss: 10, pp 809-815
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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.

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Citations
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Journal ArticleDOI

An automated high-throughput assay for survival of the nematode Caenorhabditis elegans.

TL;DR: A microtitre plate survival assay that uses uptake of the fluorescent dye SYTOX green as a marker of nematode death is developed and it is proposed that this novel method of survival analysis will accelerate the discovery of new pharmacological interventions in aging and oxidative stress.
Journal ArticleDOI

Molecular genetics of life span in C. elegans: how much does it teach us?

TL;DR: Three genes in the nematode worm Caenorhabditis elegans, age-1, daf-2 and clk-2, have now been cloned and encodes a protein of unknown biochemical function similar to the yeast metabolic regulator Cat5p/Coq7p.
Journal ArticleDOI

Aging-specific expression of Drosophila hsp22.

TL;DR: Comparison of hsp22 RNA and protein expression patterns suggests that aging-specific expression of hSp22 is regulated at both the transcriptional and the posttranscriptional levels, and indicates that functional heat shock response elements are required for hsp 22 induction during aging.
Journal ArticleDOI

Lifespan extension in genetically modified mice.

TL;DR: It is critical that a set of scientifically‐based criteria be followed to assure reliable results and establish statistically significant findings so other laboratories can replicate and build on the data.
Journal ArticleDOI

Aging, anti-aging, and hormesis.

TL;DR: The data indicate that aging is characterized by a stochastic accumulation of molecular damage and a progressive failure of maintenance and repair, and the genes involved in homeodynamic pathways are the most likely candidate virtual gerontogenes.
References
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Journal ArticleDOI

Aging: A Theory Based on Free Radical and Radiation Chemistry

TL;DR: It seems possible that one factor in aging may be related to deleterious side attacks of free radicals (which are normally produced in the course of cellular metabolism) on cell constituents.
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Pleiotropy, natural selection, and the evolution of senescence

TL;DR: August Weismann's theory is subject to a number of criticisms, the most forceful of which are: 1) The fallacy of identifying senescence with mechanical wear, 2) the extreme rarity, in natural populations, of individuals that would be old enough to die of the postulated death-mechanism, 3) the failure of several decades of gerontological research to uncover any deathmechanisms, and 4) the difficulties involved in visualizing how such a feature could be produced
Journal Article

Pleiotropy, Natural Selection, and the Evolution of Senescence

TL;DR: A new individual entering a population may be said to have a reproductive probability distribution as discussed by the authors, where the reproductive probability is zero from zygote to reproductive maturity, i.e., the individual will have no reproductive capability from birth to maturity.
Journal ArticleDOI

A C. elegans mutant that lives twice as long as wild type

TL;DR: Finding that mutations in the gene daf-2 can cause fertile, active, adult Caenorhabditis elegans hermaphrodites to live more than twice as long as wild type raises the possibility that the longevity of the dauer is not simply a consequence of its arrested growth, but instead results from a regulated lifespan extension mechanism that can be uncoupled from other aspects of dauer formation.
Journal ArticleDOI

The moulding of senescence by natural selection.

TL;DR: A basis for the theory that senescence is an inevitable outcome of evolution is established and the model shows that higher fertility will be a primary factor leading to the evolution of higher rates ofsenescence unless the resulting extra mortality is confined to the immature period.
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