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Interdisciplinary Topics in Gerontology,
1985]
The free-living, self-fertilizing hermaphroditic nematode Caenorhabditis elegans is one of the most promising and well-characterized invertebrate organisms available for the study of aging. The ease of culture and availability of a sophisticated system of genetic analysis together with the ability to grow large quantities of aged worms for biochemical analysis make this an attractive experimental system. C. elegans has recently become the subject of intense study in many areas of biology including genetics, development, muscle structure and function, gene expression, neural development, and aging. Beacuse a fixed number of cells is maintained after maturation, C. elegans is an ideal experimental system for the study of aging of post-mitotic cells. In addition, C. elegans has a transparent body with a simple anatomy that has been characterized in exquisite detail. This multicellular eucaryote develops from a single-celled zygote into a functional larva containing 558 cells comprising muscle, nerve, intestinal, hypodermal and gonadal tissues. The entire somatic cell lineage, from the singel-celled zygote to the adult containing 959 somatic cells, has been recorded. Of greatest import is that C. elegans is a genetically manipulable organism that facilitates the combination of biochemical and mutational analyses. One of the greatest series of aging studies in nematodes was that of Gershon who proposed the use of the nematode Caenorhabditis briggsae as an experimental system for the study of aging and who later described changes in enzymatic activity as well as the accumulation of lipofuszin granules and the effect of antioxidants on life span. C. briggsae and other nematode species have been used in detailed studies describing age-correlated alterations in specific activity of enzymes and protein degradation as well as in many other descriptive and analytical stuudies on aging. None of the species previously used, however, have been as well-characterized as C. elegans either genetically or anatomically. The inception of C. elegans as an experimental system for intense biological study originated with its genetic characterization by Brenner. Since then, C. elegans has been used to study the many biological processes described above including aging. Environmental effects on life span, changes in DNA structure and repair, nematode behavior, genetic recombination frequency, O2 consumption, and lipofuszin accumulation over the life span have also been studied. Mutations affecting life span have been isolated, long-lived strains have been developed using seletive breeding techniques. These studies and pertinent others are reviewed following the general description of
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International Review of Cytology,
1986]
The problem of cell-specific gene expression has long been a major concern to developmental biologists. Why and how specific genes are expressed only in certain differentiated cells and not in others are of vital importance. Many well-documented examples of differentiated cell types expressing quantitative and/or qualitative changes in gene expression now exist. For example, Galau et al. (1976) demonstrated that different sets of genes are expressed during development and in different adult tissues of the sea urchin. More recently, Angerer and Davidson (1984) have used in situ hybridization of specific DNA probes to demonstrate the expression of lineage-specific genes long before morphological differentiation. Other examples include the ovalbumin gene, known to be expressed only in hormone-stimulated oviducts, and the globin genes expressed at various developmental stages in differentiating erythrocytes. Many other examples of cell-specific gene expression are known, including the silk moth chorion proteins, the glue proteins in Drosophila, and a-amylase in mammals. Detailed molecular analysis of genes has provided important information on the mechanisms of gene expression. For example, numerous studies have examined the role of chromatin structure as well as the significance of specific sequences in the transcription and translation of eukaryotic genes. Furthermore, studies of the globin, actin, immunoglobulin, histone, and silk moth chorion genes have demonstrated the existence of gene families with suggested importance for the evolution of new functions for old genes. In addition, the detailed study of multigene families has provided vital information on the mechanisms of cell-specific gene expression as seen, for example, in the temporal and spatial regulation of different members of the actin gene family....
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Exp Gerontol,
2017]
Methionine restriction (MR) extends lifespan across different species. The main responses of rodent models to MR are well-documented in adipose tissue (AT) and liver, which have reduced mass and improved insulin sensitivity, respectively. Recently, molecular mechanisms that improve healthspan have been identified in both organs during MR. In fat, MR induced a futile lipid cycle concomitant with beige AT accumulation, producing elevated energy expenditure. In liver, MR upregulated fibroblast growth factor 21 and improved glucose metabolism in aged mice and in response to a high-fat diet. Furthermore, MR also reduces mitochondrial oxidative stress in various organs such as liver, heart, kidneys, and brain. Other effects of MR have also been reported in such areas as cardiac function in response to hyperhomocysteinemia (HHcy), identification of molecular mechanisms in bone development, and enhanced epithelial tight junction. In addition, rodent models of cancer responded positively to MR, as has been reported in colon, prostate, and breast cancer studies. The beneficial effects of MR have also been documented in a number of invertebrate model organisms, including yeast, nematodes, and fruit flies. MR not only promotes extended longevity in these organisms, but in the case of yeast has also been shown to improve stress tolerance. In addition, expression analyses of yeast and Drosophila undergoing MR have identified multiple candidate mediators of the beneficial effects of MR in these models. In this review, we emphasize other in vivo effects of MR such as in cardiovascular function, bone development, epithelial tight junction, and cancer. We also discuss the effects of MR in invertebrates.