Reduced IGF-1 Signaling Delays Age-Associated Proteotoxicity in Mice

Ehud Cohen, Johan F. Paulsson, Pablo Blinder, Tal Burstyn-Cohen, Deguo Du, Gabriela Estepa, Anthony Adame, Hang M. Pham, Martin Holzenberger, Jeffery W. Kelly, Eliezer Masliah, Andrew Dillin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The insulin/insulin growth factor (IGF) signaling (IIS) pathway is a key regulator of aging of worms, flies, mice, and likely humans. Delayed aging by IIS reduction protects the nematode C. elegans from toxicity associated with the aggregation of the Alzheimer's disease-linked human peptide, Aβ. We reduced IGF signaling in Alzheimer's model mice and discovered that these animals are protected from Alzheimer's-like disease symptoms, including reduced behavioral impairment, neuroinflammation, and neuronal loss. This protection is correlated with the hyperaggregation of Aβ leading to tightly packed, ordered plaques, suggesting that one aspect of the protection conferred by reduced IGF signaling is the sequestration of soluble Aβ oligomers into dense aggregates of lower toxicity. These findings indicate that the IGF signaling-regulated mechanism that protects from Aβ toxicity is conserved from worms to mammals and point to the modulation of this signaling pathway as a promising strategy for the development of Alzheimer's disease therapy.

Original languageEnglish
Pages (from-to)1157-1169
Number of pages13
Issue number6
StatePublished - 11 Dec 2009
Externally publishedYes




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