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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

Attenuation of NF-κB Signaling Response to UVB Light during Cellular Senescence

TL;DR: The results show that the induction of NF-κB-mediated signaling by UVB light is highly attenuated in senescent fibroblasts, which may reduce the stress resistance during cellular senescence.
Journal ArticleDOI

Overexpressed Sod1p acts either to reduce or to increase the lifespans and stress resistance of yeast, depending on whether it is Cu(2+)-deficient or an active Cu,Zn-superoxide dismutase.

TL;DR: Yeast overexpressing SOD1, the gene for Cu, Zn‐superoxide dismutase (Cu,Zn‐Sod), was used to determine how Sod1p overexpression influences the chronological lifespan, the replicative lifespan and stress resistance, showing this chronological lifespan is ultimately limited by oxidative stress.
Journal ArticleDOI

Age-Specificity of Inbreeding load in Drosophila melanogaster and Implications For the Evolution of Late Life Mortality Plateaus

TL;DR: Testing the degree of age specificity of segregating alleles affecting fitness in Drosophila melanogaster found that allelic effects are age specific with effects extending over 1–2 weeks across all age classes, consistent with modified mutation-accumulation theory.
Journal ArticleDOI

Oxidation resistance 1 is essential for protection against oxidative stress and participates in the regulation of aging in Caenorhabditis elegans

TL;DR: A homolog (LMD-3) of human OXR1 is identified in the nematode Caenorhabditis elegans and it is suggested that it contributes to the protection against oxidative stress and aging in C. elegans.
Book ChapterDOI

Stress response and aging in Caenorhabditis elegans.

TL;DR: Mutants of C. elegans that exhibit extraordinarily long life-spans are proving a rich source of information on the molecular determinates of aging rate, including resistance to a variety of extrinsic environmental stresses.
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.
Journal ArticleDOI

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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