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Long-Term IGF-I Exposure Decreases Autophagy and Cell Viability
Journal article   Open access   Peer reviewed

Long-Term IGF-I Exposure Decreases Autophagy and Cell Viability

Alessandro Bitto, Chad Lerner, Claudio Torres, Michaela Roell, Marco Malaguti, Viviana Perez, Antonello Lorenzini, Silvana Hrelia, Yuji Ikeno, Michelle Elizabeth Matzko, …
PloS one, v 5(9), pp 1-10
07 Sep 2010
PMID: 20830296
url
https://doi.org/10.1371/journal.pone.0012592View
Published, Version of Record (VoR)CC BY V4.0 Open

Abstract

Aging Cell Biology Cell Signaling Cellular Death and Stress Responses Developmental Biology
A reduction in IGF-I signaling has been found to increase lifespan in multiple organisms despite the fact that IGF-I is a trophic factor for many cell types and has been found to have protective effects against multiple forms of damage in acute settings. The increase in longevity seen in response to reduced IGF-I signaling suggests that there may be differences between the acute and chronic impact of IGF-I signaling. We have examined the possibility that long-term stimulation with IGF-I may have a negative impact at the cellular level using quiescent human fibroblasts. We find that fibroblast cells exposed to IGF-I for 14 days have reduced long-term viability as judged by colony forming assays, which is accompanied by an accumulation of senescent cells. In addition we observe an accumulation of cells with depolarized mitochondria and a reduction in autophagy in the long-term IGF-I treated cultures. An examination of mice with reduced IGF-I levels reveals evidence of enhanced autophagy and fibroblast cells derived from these mice have a larger mitochondrial mass relative to controls indicating that changes in mitochondrial turnover occurs in animals with reduced IGF-I. The results indicate that chronic IGF-I stimulation leads to mitochondrial dysfunction and reduced cell viability.

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Domestic collaboration
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Web of Science research areas
Biochemistry & Molecular Biology
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