title: Long-term IGF-I exposure decreases autophagy and cell viability.
abstract: 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.
authors.affiliation: Department of Pathology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bitto
authors.forename: Chad
authors.initials: C
authors.lastname: Lerner
authors.forename: Claudio
authors.initials: C
authors.lastname: Torres
authors.forename: Michaela
authors.initials: M
authors.lastname: Roell
authors.forename: Marco
authors.initials: M
authors.lastname: Malaguti
authors.forename: Viviana
authors.initials: V
authors.lastname: Perez
authors.forename: Antonello
authors.initials: A
authors.lastname: Lorenzini
authors.forename: Silvana
authors.initials: S
authors.lastname: Hrelia
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ikeno
authors.forename: Michelle Elizabeth
authors.initials: ME
authors.lastname: Matzko
authors.forename: Roger
authors.initials: R
authors.lastname: McCarter
authors.forename: Christian
authors.initials: C
authors.lastname: Sell
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D002470:Cell Survival; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism
chemical_list: D007334:Insulin-Like Growth Factor I