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[
Biogerontology,
2019]
Aging is a natural and unavoidable part of life. However, aging is also the primary driver of the dominant human diseases, such as cardiovascular disease, cancer, and neurodegenerative diseases, including Alzheimer's disease. Unraveling the sophisticated molecular mechanisms of the human aging process may provide novel strategies to extend 'healthy aging' and the cure of human aging-related diseases. Werner syndrome (WS), is a heritable human premature aging disease caused by mutations in the gene encoding the Werner (WRN) DNA helicase. As a classical premature aging disease, etiological exploration of WS can shed light on the mechanisms of normal human aging and facilitate the development of interventional strategies to improve healthspan. Here, we summarize the latest progress of the molecular understandings of WRN protein, highlight the advantages of using different WS model systems, including Caenorhabditis elegans, Drosophila melanogaster and induced pluripotent stem cell (iPSC) systems. Further studies on WS will propel drug development for WS patients, and possibly also for normal age-related diseases.
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[
Cells,
2021]
Werner syndrome (WS) is a rare recessive genetic disease characterized by premature aging. Individuals with this disorder develop normally during childhood, but their physiological conditions exacerbate the aging process in late adolescence. WS is caused by mutation of the human WS gene (<i>WRN</i>), which encodes two main domains, a 3'-5' exonuclease and a 3'-5' helicase. <i>Caenorhabditis elegans</i> expresses human WRN orthologs as two different proteins: MUT-7, which has a 3'-5' exonuclease domain, and <i>C</i><i>. elegans</i> WRN-1 (CeWRN-1), which has only helicase domains. These unique proteins dynamically regulate olfactory memory in <i>C. elegans</i>, providing insight into the molecular roles of WRN domains in humans. In this review, we specifically focus on characterizing the function of MUT-7 in small interfering RNA (siRNA) synthesis in the cytoplasm and the roles of siRNA in directing nuclear CeWRN-1 loading onto a heterochromatin complex to induce negative feedback regulation. Further studies on the different contributions of the 3'-5' exonuclease and helicase domains in the molecular mechanism will provide clues to the accelerated aging processes in WS.
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[
J Exp Zool,
1999]
A memorable workshop, focused on causal mechanisms in metazoan evolution and sponsored by NASA, was held in early June 1998, at MBL. The workshop was organized by Mike Levine and Eric H. Davidson, and it included the PI and associates from 12 different laboratories, a total of about 30 people. Each laboratory had about two and one half hours in which to represent its recent research and cast up its current ideas for an often intense discussion. In the following we have tried to enunciate some of the major themes that emerged, and to reflect on their implications. The opinions voiced are our own. We would like to tender apologies over those contributions we have not been able to include, but this is not, strictly speaking, a meeting review. Rather we have focused on those topics that bear more directly on evolutionary mechanisms, and have therefore slighted some presentations (including some of our own), that were oriented mainly toward developmental processes. J. Exp. Zool. (Mol. Dev. Evol. ) 285:104-115, 1999.
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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....