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Crit Rev Biochem Mol Biol,
2014]
Members of the class B1 family of G-protein coupled receptors (GPCRs) whose ligands are neuropeptides have been implicated in regulation of circadian rhythms and sleep in diverse metazoan clades. This review discusses the cellular and molecular mechanisms by which class B1 GPCRs, especially the mammalian VPAC2 receptor and its functional homologue PDFR in Drosophila and C. elegans, regulate arousal and daily rhythms of sleep and wake. There are remarkable parallels in the cellular and molecular roles played by class B1 intercellular signaling pathways in coordinating arousal and circadian timekeeping across multiple cells and tissues in these very different genetic model organisms.
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Mech Ageing Dev,
2002]
In 1967, as we became interested in the biology of aging, we were faced with the following basic biological paradox: organisms are endowed with the capacity to detect and repair damage encountered at the molecular and cellular levels and yet functional capacity declines with time. In accordance with Strehler's suggestion (Time, Cells, and Aging, 2nd ed., Academic Press, New York, 1962), we adopted the basic premise that the underlying mechanisms of aging are common to all multi-cellular organisms. A search for a suitable experimental organism that fulfills the basic criteria for an appropriate model for aging research (Exp. Gerontol. 5 (1970) 7; Mech. Ageing Dev. 117 (2000) 21) led us to the selection of nematodes as a model for our initial series of experiments. Nematodes have thus been used in aging research for three decades. This review critically examines the major merits and shortcomings of this model organism for aging research and argues for greater appreciation of the need to understand the biology of the nematode life cycle not only as it is maintained in the laboratory, but also as it evolved and lives in nature.