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Pharmacological analysis of aging in...

Evason, Kimberley Jane.

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Pharmacological analysis of aging in Caenorhabditis elegans.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Pharmacological analysis of aging in Caenorhabditis elegans./
作者:	Evason, Kimberley Jane.
面頁冊數:	152 p.
附註:	Adviser: Kerry Kornfeld.
Contained By:	Dissertation Abstracts International68-06B.
標題:	Biology, Molecular. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3268026
ISBN:	9780549070610

Pharmacological analysis of aging in Caenorhabditis elegans.
Evason, Kimberley Jane.

Pharmacological analysis of aging in Caenorhabditis elegans. - 152 p.

Adviser: Kerry Kornfeld.

Thesis (Ph.D.)--Washington University in St. Louis, 2007.

The molecular mechanisms that regulate aging are beginning to be discovered, and it is clear that many key features of human aging are conserved in shorter-lived species including C. elegans. To investigate mechanisms that regulate aging, we identified and characterized pharmacological compounds that extend C. elegans lifespan.

ISBN: 9780549070610Subjects--Topical Terms:

1017719
Biology, Molecular.

Pharmacological analysis of aging in Caenorhabditis elegans.
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245 1 0 $a Pharmacological analysis of aging in Caenorhabditis elegans.
300 $a 152 p.
500 $a Adviser: Kerry Kornfeld.
500 $a Source: Dissertation Abstracts International, Volume: 68-06, Section: B, page: 3558.
502 $a Thesis (Ph.D.)--Washington University in St. Louis, 2007.
520 $a The molecular mechanisms that regulate aging are beginning to be discovered, and it is clear that many key features of human aging are conserved in shorter-lived species including C. elegans. To investigate mechanisms that regulate aging, we identified and characterized pharmacological compounds that extend C. elegans lifespan.
520 $a The anticonvulsant medications ethosuximide and trimethadione extended C. elegans lifespan and delayed age-related degenerative changes. These heterocyclic ring compounds affected C. elegans neuromuscular behaviors, including body movement and egg laying. A structurally similar compound that is not an anticonvulsant did not extend lifespan. The level of ethosuximide inside C. elegans cultured with a life-extending dose of drug was similar to the therapeutic level in humans treated for seizures. Ethosuximide and trimethadione extended lifespan of worms with mutations in genes that affect known aging pathways, indicating the anticonvulsant action is different from the action of these mutations. Our studies suggest that ethosuximide extends lifespan by altering neural activity, and support the hypothesis that the nervous system regulates aging. In addition, ethosuximide and trimethadione delayed reproductive aging without decreasing progeny production, suggesting that early reproduction does not cause reproductive or somatic aging.
520 $a The mood stabilizer and anticonvulsant valproic acid extended C. elegans lifespan and delayed some age-related degenerative changes. This carboxylic acid caused different non-aging phenotypes than ethosuximide, including enhancement of dauer formation. Worms cultured with valproic acid and ethosuximide lived longer than worms treated with either drug alone. Together, this evidence supports the hypothesis that valproic acid has a mechanism of action that is different from that of ethosuximide and trimethadione.
520 $a To identify genes that mediate the effects of ethosuximide and trimethadione, we conducted a forward genetic screen for mutations that cause resistance to these compounds. We isolated 52 mutants that were resistant to the lethality caused by high doses of ethosuximide or trimethadione. Some of these mutants were long-lived and/or resistant to the lifespan extension caused by the drugs, suggesting the affected genes might regulate aging and/or mediate the lifespan extension of the anticonvulsants. The molecular characterization of such genes may elucidate how the drugs extend lifespan and how normal aging is regulated.
590 $a School code: 0252.
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650 4 $a Health Sciences, Pharmacology. $3 1017717
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710 2 $a Washington University in St. Louis. $3 1017519
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790 $a 0252
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791 $a Ph.D.
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