Three components that have each been associated separately with the aging process in worm or rodent model systems have now been linked together by Nemoto and Finkel in a mammalian signaling pathway that may regulate longevity. An increase in intracellular oxidants decreased the activity of a forkhead transcription factor, whose inhibition has been implicated in aging. This effect required expression of the intracellular protein p66shc. Preservation of forkhead activity resulted in higher oxidant scavenging and a decrease on overall cellular oxidant levels. The use of reactive oxygen species as signaling agents may have important therapeautic implications.
S. Nemoto, T. Finkel, Redox regulation of forkhead proteins through a p66shc-dependent signaling pathway. Science 295: 2450-2452 (2002). [Abstract] [Full Text]
