iansmith
Dec11-03, 09:54 PM
DAF and TOR systems act in concert to regulate lifespan and growth | By Cathy Holding
Size and lifespan are under control of insulin and insulin-like growth factors (DAF2/IGFs)—that regulate proliferation and differentiation in many body systems—and also the Tor kinase family of proteins, which have a role in nutrient sensing and response to starvation. Both systems are highly conserved across species and time, but the observation that both act on longevity in Caenorhabditis elegans in similar ways at similar times prompted Tibor Vellai and colleagues at the University of Fribourg to investigate the possibility that they may act together. In the December 11 Nature, they report the concerted action of these two systems and a novel role for the Tor protein kinases in nutrition, metabolism, and longevity (Nature, 426:620, December 11, 2003).
Vellai et al. examined the effects of gene knockout induced both by breeding and by RNA inhibition in the nematode and observed that absence of TOR kinase activity resulted in arrest and survival at the L3 larval stage for 25 days, as opposed to the usual lifespan of only 10 days. The authors demonstrated that this was not due to reduction in mitochondrial activity. Worms deficient in DAF-2 also exhibited doubling of lifespan that could not be extended by RNA inhibition of TOR activity. Starvation and crowding in wildtype worms resulted in a development pause that was mimicked by knockout of DAF-2 and enhanced by inhibition of TOR, indicating a collaborative role for these two systems. Further studies indicated that TOR activity is downstream of the Forkhead transcription factor DAF-16 and interacts directly with the insulin endocrine system.
“Although the detailed signaling connections require clarification, our findings point to TOR as a possible mediator of lifespan regulation by insulin signaling and nutrient sensing,” the authors conclude.
Links for this article
N.S. Cutler et al., “The TOR signal transduction cascade controls cellular differentiation in response to nutrients,” Molecular Biology of the Cell, 12: 4103-4113, December 2001.
[PubMed Abstract]
University of Fribourg
http://www.unifr.ch/home/welcomeE.html
T. Vellai et al., “Influence of TOR kinase on lifespan in C. elegans,” Nature, 426:620, December 11, 2003.
http://www.nature.com/nature
http://www.biomedcentral.com/news/20031211/01
Size and lifespan are under control of insulin and insulin-like growth factors (DAF2/IGFs)—that regulate proliferation and differentiation in many body systems—and also the Tor kinase family of proteins, which have a role in nutrient sensing and response to starvation. Both systems are highly conserved across species and time, but the observation that both act on longevity in Caenorhabditis elegans in similar ways at similar times prompted Tibor Vellai and colleagues at the University of Fribourg to investigate the possibility that they may act together. In the December 11 Nature, they report the concerted action of these two systems and a novel role for the Tor protein kinases in nutrition, metabolism, and longevity (Nature, 426:620, December 11, 2003).
Vellai et al. examined the effects of gene knockout induced both by breeding and by RNA inhibition in the nematode and observed that absence of TOR kinase activity resulted in arrest and survival at the L3 larval stage for 25 days, as opposed to the usual lifespan of only 10 days. The authors demonstrated that this was not due to reduction in mitochondrial activity. Worms deficient in DAF-2 also exhibited doubling of lifespan that could not be extended by RNA inhibition of TOR activity. Starvation and crowding in wildtype worms resulted in a development pause that was mimicked by knockout of DAF-2 and enhanced by inhibition of TOR, indicating a collaborative role for these two systems. Further studies indicated that TOR activity is downstream of the Forkhead transcription factor DAF-16 and interacts directly with the insulin endocrine system.
“Although the detailed signaling connections require clarification, our findings point to TOR as a possible mediator of lifespan regulation by insulin signaling and nutrient sensing,” the authors conclude.
Links for this article
N.S. Cutler et al., “The TOR signal transduction cascade controls cellular differentiation in response to nutrients,” Molecular Biology of the Cell, 12: 4103-4113, December 2001.
[PubMed Abstract]
University of Fribourg
http://www.unifr.ch/home/welcomeE.html
T. Vellai et al., “Influence of TOR kinase on lifespan in C. elegans,” Nature, 426:620, December 11, 2003.
http://www.nature.com/nature
http://www.biomedcentral.com/news/20031211/01