Invited Symposium: Molecular Mechanisms of Ageing
Murakami, S. (I.B.G., University of Colorado at Boulder, USA)
Cypser, J (I.B.G., University of Colorado at Boulder, USA)
Link, C (I.B.G., University of Colorado at Boulder, USA)
Rikke, B (I.B.G., University of Colorado at Boulder, USA)
Tedesco, P (I.B.G., University of Colorado at Boulder, USA)
Several mutants in Caenorhabditis elegans lead to increased life span; these are referred to as 'Age' mutants. All Age mutants must identify genes (called gerontogenes) that have been altered such that key functions limiting life span are identified. Age mutants increase the ability of the worm to respond to a variety of stresses: heat, UV, and reactive oxidants. Several of these gerontogenes code for proteins involved in signal transduction. tkr-1-overexpressing strains are stress resistant and long-lived. tkr-1 has significant homology with many mammalian RTKs, including C -kit and FGFR.. Not all RTKs are gerontogenes. Using tkr-1::GFP fusions, we find that tkr-1 is upregulated after exposure to heat, UV or starvation; thus, tkr-1 may be involved in a novel signal-transduction pathway modulating intracellular response to a variety of stresses. tkr-1 appears to represent a novel family of tyrosine kinases not before reported. A major evolutionary determinant of longevity is the ability to respond to stress. In mammals, both dietary restriction and hormesis are phenomena in which the endogenous level of resistance to stress has been upregulated; numerous studies show that both of these interventions can result in extended longevity. We have also shown that defective strains that fail to induce increased resistance to stress also modulate gerontogenes. The Age mutants may reveal important, evolutionarily-conserved components of longevity/stress-response pathways that have been conserved between nematodes and mammals.
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|Johnson, T.E.; Murakami, S.; Cypser, J; Link, C; Rikke, B; Tedesco, P; (1998). Genetic Manipulation of Longevity in C. elegans Through Increased Response to Stress. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/higuchi/johnson0498/index.html|
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