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First published online October 12, 2006

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Ageing – ay, there's the Rheb

Stress – particularly oxidative stress – is probably a major contributing factor in ageing, cancer and neurodegenerative conditions. It damages DNA and other key macromolecules and must be combated by various cellular defence mechanisms. Another factor linked to ageing is target of rapamycin (TOR) signalling – a pathway in which insulin, the GTPase Rheb, the TOR protein and S6 kinase (S6K) regulate protein synthesis and cell growth. On p. 4285, Parthive Patel and Fuyuhiko Tamanoi demonstrate that the two are connected. By overexpressing Rheb, TOR or a constitutively active mutant of S6K, they show that increasing TOR signalling sensitizes flies to various stresses. When faced with oxidative stress caused by H₂O₂ or paraquat, for example, the flies become less mobile (through senescence of motor activity) and die prematurely. They are similarly sensitive to starvation-induced stress. The authors confirm this is due to TOR signalling by showing that an inactive S6K mutant can block the effects and that expression of TSC2 (a negative regulator of the pathway) confers resistance to stress. Since Rheb-TOR signalling is increased by elevated insulin levels and nutrient availability and in certain disease states, this link could be highly important in ageing and pathological conditions.

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Related articles in JCS:

Increased Rheb-TOR signaling enhances sensitivity of the whole organism to oxidative stress

Parthive H. Patel and Fuyuhiko Tamanoi
JCS 2006 119: 4285-4292. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?