title: IGF1R levels in the brain negatively correlate with longevity in 16 rodent species.
abstract: The insulin/insulin-like growth factor signaling (IIS) pathway is a major conserved regulator of aging. Nematode, fruit fly and mouse mutants with reduced IIS signaling exhibit extended lifespan. These mutants are often dwarfs leading to the idea that small body mass correlates with longevity within species. However, when different species are compared, larger animals are typically longer-lived. Hence, the role of IIS in the evolution of life history traits remains unresolved. Here we used comparative approach to test whether IGF1R signaling changes in response to selection on lifespan or body mass and whether specific tissues are involved. The IGF1R levels in the heart, lungs, kidneys, and brains of sixteen rodent species with highly diverse lifespans and body masses were measured via immunoblot after epitope conservation analysis. We report that IGF1R levels display strong negative correlation with maximum lifespan only in brain tissue and no significant correlations with body mass for any organ. The brain-IGF1R and lifespan correlation holds when phylogenetic non-independence of data-points is taken into account. These results suggest that modulation of IGF1R signaling in nervous tissue, but not in the peripheral tissues, is an important factor in the evolution of longevity in mammals.
authors: Department of Biology, University of Rochester, Rochester, NY 14627, USA.
authors: Jorge
authors: J
authors: Azpurua
authors: Jiang-Nan
authors: JN
authors: Yang
authors: Michael
authors: M
authors: Van Meter
authors: Zhengshan
authors: Z
authors: Liu
authors: Julie
authors: J
authors: Kim
authors: Aliny A B
authors: AA
authors: Lobo Ladd
authors: Antonio Augusto
authors: AA
authors: Coppi
authors: Vera
authors: V
authors: Gorbunova
authors: Andrei
authors: A
authors: Seluanov
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D017124:Conserved Sequence; D000939:Epitopes; D008969:Molecular Sequence Data; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012377:Rodentia / Q000145:classification* / Q000378:metabolism* / Q000502:physiology; D016415:Sequence Alignment; D013045:Species Specificity
chemical_list: D000939:Epitopes; D017526:Receptor, IGF Type 1
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