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[
1983]
In 1974, Sydney Brenner published an elegant paper that described the genetic system of Caenorhabditis elegans and led to its use in research on a wide variety of topics, including aging (Brenner, 1974). Its small size (1mm as an adult) and determinate cell lineage has allowed a description of the entire somatic cell lineage from the one-cell stage to the adult (Sulston and Horvitz, 1977; Deppe et al., 1978; Kimble and Hirsh, 1979; Suslton et al., personal communication). Its ease of culture makes it an organism of choice for studies of various aspects of anatomy and physiology, including muscle formation and function (Zengel and Epstein, 1980; Mackenzie and Epstein, 1980), cuticle formation (Cox et al, 1981), neuroanatomy (Ward et al, 1975; Ware et al, 1975; Sulston et al, 1975), and behavior (Dusenbery, 1980). Several genes have been cloned by recombinant DNA techniques ablation (Kimble, 1981; Laufer and von Ehrenstin, 1981) procedures, as well as most of the modern molecular techniques, are in use.
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Exp Gerontol,
1997]
Genetics is an important tool for identifying key molecular events that are involved in specifying biological functions. Genetic approaches have been used repeatedly to understand diverse biological phenomena: oncogenesis, development, and the cell cycle, but have only recently been applied to the analysis of organismic aging and senescence. The power of the genetic approach stems from two facts. First, genetic analyses allow the integration of phenomena that are analyzed at many levels of observation from the molecule to the intact organism, and second, genetics has the real power to reveal causality by factors that are not dependent upon the prejudice of the investigator. I discuss several areas where genetics has been fruitfully applied to the study of the aging processes: human genes identified by "segmental progeroid" mutations, neurological diseases of the elderly, the limited proliferative life span of human somatic cells in tissue culture, studies on the life span of the mouse, and genetic analysis of life span in shorter lived metazoans (Drosophila melanogaster and Caenorhabditis elegans), and the yeast Saccharomyces cerevisiae.
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Biogerontology,
2002]
This is a personal account of the early days in the genetic analysis of aging when it was difficult to persuade the world that there were genes that specified life prolongation. I describe the situation in 1980 and briefly describe the background of early work on the nematode Caenorhabditis elegans and my role in the revolution in aging research that has occurred in the last 20 years.
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[
Bioessays,
1998]
Sometimes genes are arranged nonrandomly on the chromosomes of eukaryotes. This review considers instances of gene clusters in which two genes or more are expressed from a single promoter. This includes cases in which a polycistronic pre-mRNA is processed to make monocistronic mRNAs in nematodes, as well as isolated examples of polycistronic mRNAs found in mammals, flies, and perhaps plants.
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[
BioEssays,
1993]
In trans-splicing, the pre-mRNA products of two different genes are spliced together to form a single, mature mRNA. In one type of trans-splicing, pre-mRNAs of many different genes receive a single, short leader, called spliced leader or SL. This type of trans-splicing was first discovered in the primitive eukaryotes, the trypanosomes, where it is apparently the only kind of nuclear mRNA splicing. Subsequently, it was discovered in nematodes (round worms), trematodes (flat worms), and euglena. Although this type of trans-splicing has never been found in any of the other well-studied organisms, Bruzik and Maniatis have recently reported that mammalian cells are capable of performing the reaction when they are provided with the appropriate pre-mRNAs.
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Trends Genet,
1995]
Caenorhabditis elegans engages in three distinct versions of nuclear pre-mRNA splicing: cis-splicing of introns and two kinds of trans-splicing that result in the addition of two different spliced leaders onto mRNAs. One leader (SL1) is used near the 5' ends of pre-mRNAs while the other (SL2) is used at internal trans-splice sites of polycistronic pre-mRNAs. Here, I consider bow these three types of splicing event are faithfully carried out.
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Exp Gerontol,
2003]
The nematode Caenorhabditis elegans has been the organism of choice for most aging research, especially genetic approaches to aging. More than 70 longevity genes have been identified, with more to come, and these genes have been the subjects of intense study. I identify the major reasons for this and discuss limitations of this organism for future progress in research on aging.
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Exp Gerontol,
2008]
This is the 25th anniversary of the discovery of extended longevity mutants in Caenorhabditis elegans. About one hundred papers describing results from studies on C. elegans in aging research appeared this year. Many themes were pursued including dietary restriction,
daf-9 action, the role of proteolysis and autophagy, and the continued search for more Age mutants. I use the word "modulate" not "regulate" so as to be consistent with the evolutionary theory of aging, which is also consistent with the empirical findings of all extended longevity (Age) mutants. These Age mutants universally result from deficits in known physiologic systems, rather than in some process designed to kill the animal in old age.
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Journal of Gerontology,
1988]
Genetic approaches have been used to gain insights into many complex biological phenomena, but until recently most attempts to use genetic approaches to understand aging or senescence processes in metazoans have met with little success. The first review in this series (Martin and Tucker, 1988) surveyed model organisms used in the genetic analysis of aging; here I will review the analysis of life span and of the aging process by means of genetics. Problems inherent in the genetic analysis of aging will be reviewed first. Successful applications of genetics to the phenomena of aging will next be highlighted. Finally, I will present examples of ways in which both molecular and classical genetic approaches can be fruitfully and realistically applied to the study of the aging processes. Where applicable, misinterpretations and possible future directions will be noted.
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Trends Genet,
1988]
Nematodes are the only organisms in which both cis- and trans-splicing of nuclear mRNAs are known to occur. Despite some unusual characteristics of introns in C. elegans, the nematode splicing machinery is quite similar to that described in other organisms. Nematodes contain a novel snRNP, the RNA moiety of which donates its 5' end to many different transcripts by trans-splicing. In the course of molecular analysis of developmentally interesting genes in the nematode Caenorhabditis elegans, some intriguing observations have been made regarding RNA splicing. Most interesting is the discovery that some, but not all, actin mRNAs receive a 22-nucleotide leader sequence by trans-splicing. In nematodes, the same mRNAs are substrates for both cis- and trans-splicing. This juxtaposition offers a unique opportunity to study the relationship between these two types of reactions. In this review we summarize some unique characteristics of cis-spliced introns in C. elegans as well as data suggesting that this nematode has a typical array of snRNPs. We describe the discovery of trans-splicing in the actin gene family and summarize results showing that many other mRNAs are also trans-spliced. Finally, observations bearing on the mechanism and function of trans-splicing in C. elegans are considered.