'The rate of living' hypothesis of aging speculates that the metabolic rate of a species ultimately determines its life expectancy. Using the nematode worm Caenorhabditis elegans as model system, mutation in twp-1 (t&barbelow;ime w&barbelow;arp) gene was found to significantly delay biological timing and remarkably increase mean and maximum life span. The rate of living in twp-1 is dramatically delayed in all the biological processes we tested, including rates of rhythmic adult behaviors, development, and reproduction. Oxygen consumption, which indicates metabolic rate of an organism, is reduced to approximately two-fold in twp-1 mutant. According to my study, twp-1 and dauer genes, daf-2 and daf-16, interact to determine biological timing and adult life span. twp-1 mutation prolongs life span in a way that is at least partially different from dauer formation mutants, whose longevity might due to their high resistance to stresses, especially oxidative stress. twp-1 gene is cloned and found to encode iron-sulfur protein (ISP) in complex III, which is the major site of mitochondrial superoxide radical production, of the mitochondrial respiratory chain. This suggests that twp-1 may live long because they produce less reactive oxygen species (ROS), and thus, result in less oxidative damage. mts-1 (mitochondrial twp-1 suppressor) mutation can fully or partially rescue most of the biological timing in twp-1 mutant, including both developmental and behavioral rates, but except life span. mts-1 encodes another subunit of complex III, cytochrome b, which normally interact with ISP during function. mts-1 might somehow restore the activity of complex III, and consequently, accelerate the rate of living. Paraquat, a herbicide that induces the formation of superoxide, was used to provide an acute oxidative stress to animals. twp-1; mts-1 was found to be highly resistant to paraquat, indicating that twp-1 animals are well capable of coping with oxidative stress. According to o
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.32991 |
| Date | January 2001 |
| Creators | Feng, Jinliu, 1974- |
| Contributors | Hekimi, Siegfried (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Biology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001847001, proquestno: MQ75306, Theses scanned by UMI/ProQuest. |
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