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[
1987]
To my knowledge, a theory of "developmentally programmed aging" has never been explicitly stated, although the notion that aging has some relationship to development has certainly been proposed many times. In the preceding chapter (36), Dr. Hayflick has made a brief description of the central idea of developmental programming within aging. In order to discuss relevant evidence in this chapter, I would like to propose the following, somewhat more specific and operational definition: The theory of developmentally programmed aging posits that aging involves events controlled in ways recognizably similar to those that operate during development. This definition is perhaps a little less extreme than it might have been, since it uses the phrase "aging involves events" rather than the phrase "aging is caused by events." However, I think it captures most of the usual connotations of "developmentally programmed aging," and it at least has the virtue of testability. Of course, to test the theory, as defined, requires evidence of several sorts. In particular, it requires (a) that we understand how some aging events are controlled, (b) that we understand how some developmental events are controlled, and (c) that we know how to recognize whether there is or is not similarity between the two. A central message of what follows is that we are really only at the beginning of being able to test this theory, although some lines of approach do appear
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[
1981]
This chapter is in part a review of the work of others and in part a summary of recent results from our own laboratory. It attempts to cover the currently available information on apparent neurotransmitters in the small soil nematode Caenorhabditis elegans, whose advantages of genetic manipulability and cellular simplicity have recently gained it some favor in investigations of genetic control mechanisms in neural development (for review, see Riddle, 1978). Particular attention is given to mutants that affect either the level or the action of apparent neurotransmitters, since it seems likely that such mutants may have the most to offer toward the understanding of human genetic neuropathies. The general features of C. elegans are described briefly at the outset, then each apparent neurotransmitter is considered in turn, and finally a few potential implications for other organisms
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[
International C. elegans Meeting,
1981]
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[
1977]
Radiochemical assays based on the selective extraction of either substrate or product from an aqueous reaction volume into an organic scintillator have been developed for acetylcholinesterase and choline acetyltransferase. These rapid, convenient assays have made it possible to screen large numbers of mutant lines for potential enzymatic defects. One mutant with a partial acetylcholinesterase defect and two more with choline acetyltransferase defective mutants have been identified. The acetylcholinesterase defective mutant lacks two of the four isozymic forms of acetylcholinesterase found in wild type C. elegans. Behaviorally, it is selectively defective in the propagation of contractile waves in the body region. Of the two mutants with choline acetyltransferase defects, one is remarkabley paralyzed and uncoordinated, while the other is behaviorally nearly normal.
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[
1985]
Studies of aging in nematodes are based largely on the hope that there are some general mechanisms of aging which can be expeditiously revealed in simple multicellular organisms. Although differing greatly from mammals in size, body plan, and some organ systems, nematodes nontheless strongly resemble other metazoans at the cellular, subcellular, and biochemical levels. Moreover, nematodes do exhibit some rather widespread aging phenomena, such as nutritional prolongation of life span, accumulation of age pigments, and enzyme alterations, and their short life span, cellular simplicity, and genetic manipulability can be real advantages in studying the mechanisms underlying these phenomena.
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[
International C. elegans Meeting,
1981]
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[
Worm Breeder's Gazette,
1977]
Starting with the published anatomy of the ventral nerve cord (White et al., 1976), we have developed a model for contractile wave propagation in C. elegans. This model attempts to rationalize the known circuitry of the ventral cord with several known features of C . elegans movement, most notably the ability of waves to propagate at different rates and in opposite directions, and the ability of the animal to reverse immediately from an existing waveform. The central features of the model are that the O motor neurons act inhibitorily to keep dorsal and ventral sides in anti-coordination, that both the A and the B motor neurons act excitatorily to facilitate wave propagation, that the A motor neurons are active during backward movement while the B motor neurons are active during forward movement, that the long, 'undifferentiated' portions of the A and B motor neurons adjacent to their neuromuscular outputs are stretch sensors, and that the alpha and interneurons act as 'command fibers' for the A and B motorneurons respectively. This model accounts satisfactorily for several otherwise difficult features of movement, and seems in accord with what is known about sensory inputs that can affect movement; it also makes an interesting suggestion about the lineage division which separates the VA and VB motorneurons. Building on Stretton's (personal communication) report of a commissural 'repeat unit' in Ascaris and Sulston's (1976) lineage study of the C. elegans central cord, we have examined the notion that the motor neurons of C. elegans and Ascaris might be very similar. Under this assumption, we predicted that the commissure repeat unit of Ascaris should contain Ascaris homologs of 1 DA, 1 DE, 1 DD, 2 VD and 2 DAS cells. By initial stimulation near the lateral line and by later use of preparations from which broad muscle strips had been removed to expose the commissures, we stimulated individual commissures or commissure pairs in Acaris and determined the nature of any observed effect on muscles (dorsal or Ventral, excitatory or inhibitory). The results strongly suggest that the DD and VD cells are inhibitory, whereas the DA and DAS cells are strongly excitatory and the DB cells are weakly so. These results are predicted by the model.
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[
International C. elegans Meeting,
1977]
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[
International C. elegans Meeting,
1979]
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[
International C. elegans Meeting,
1979]