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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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Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology

TL;DR: This work discloses that expression of Hsps can occur in nature, all species have hsp genes but they vary in the patterns of their expression, and Hsp expression can be correlated with resistance to stress, and species' thresholds for HSP expression are correlated with levels of stress that they naturally undergo.
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Phosphoinositide 3-kinases: a conserved family of signal transducers.

TL;DR: Phosphoinositide 3-kinases generate lipids that are implicated in receptor-stimulated signalling and in the regulation of membrane traffic and their potential signalling pathways have been elucidated and PI3K function is now being characterised in several model organisms.
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The role of oxidative damage and stress in aging.

TL;DR: The most direct test of the Free Radical/Oxidative Stress Theory of Aging is to specifically alter the age-related increase in oxidative damage and determine how this alteration affects life span.
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Genotype-environment interaction for quantitative trait loci affecting life span in Drosophila melanogaster.

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.
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Type 5 Adenylyl Cyclase Disruption Increases Longevity and Protects Against Stress

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 ArticleDOI

Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress.

TL;DR: The results suggest that ability to respond to stress limits the life expectancy of C. elegans and might do so in other metazoa as well, and the relationship between increased thermotolerance and increased life-span is investigated.
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TL;DR: The free radical theory of aging postulates that aging changes are caused by free radical reactions, and data indicate that average life expectancy at birth may be increased by 5 or more years, by nutritious low caloric diets supplemented with one or more free radical reaction inhibitors.
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The Evolution of Ageing and Longevity

TL;DR: This ‘disposable soma’ theory of the evolution of ageing also proposes that a high level of accuracy is maintained in immortal germ line cells, or alternatively, that any defective germ cells are eliminated.
Journal ArticleDOI

Aging and resistance to oxidative damage in Caenorhabditis elegans.

TL;DR: Results support the free radical theory of aging by suggesting that the increased resistance to oxidative stress may be among the causes of increased longevity in both strain TJ401 and in the dauer larva.
Journal ArticleDOI

A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues.

TL;DR: An assay that selectively amplifies a specific deletion of the mitochondrial genome has been used to study the extent of the deletion's accumulation in a variety of human tissues, and three cellular parameters that are correlated with the level of the delete are identified.
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