Article

Insulin/IGF-I-signaling pathway: An evolutionarily conserved mechanism of longevity from yeast to humans

University of Bologna, Bolonia, Emilia-Romagna, Italy
AJP Endocrinology and Metabolism (Impact Factor: 3.79). 12/2003; 285(5):E1064-71. DOI: 10.1152/ajpendo.00296.2003
Source: PubMed

ABSTRACT

Although the underlying mechanisms of longevity are not fully understood, it is known that mutation in genes that share similarities with those in humans involved in the insulin/insulin-like growth factor I (IGF-I) signal response pathway can significantly extend life span in diverse species, including yeast, worms, fruit flies, and rodents. Intriguingly, the long-lived mutants, ranging from yeast to mice, share some important phenotypic characteristics, including reduced insulin signaling, enhanced sensitivity to insulin, and reduced IGF-I plasma levels. Such genetic homologies and phenotypic similarities between insulin/IGF-I pathway mutants raise the possibility that the fundamental mechanism of aging may be evolutionarily conserved from yeast to mammals. Very recent findings also provide novel and intriguing evidence for the involvement of insulin and IGF-I in the control of aging and longevity in humans. In this study, we focus on how the insulin/IGF-I pathway controls yeast, nematode, fruit fly, and rodent life spans and how it is related to the aging process in humans to outline the prospect of a unifying mechanism in the genetics of longevity.

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    • "Therefore, signaling pathways involving in apoptosis/differentiation may play roles in metamorphosis. Insulin/insulin-like growth factor signaling pathway (IIS) is well conserved from yeast to humans (Barbieri et al., 2003), and plays important roles in diverse biological processes, such as growth, energy metabolism, and development. IIS contains secreted ligands Aquaculture 451 (2016) 377–384 Abbreviations: BC, blank control; Dilp, Drosophila insulin-like peptide; dsRNA, doublestranded RNA; FSW, filtered seawater; GABA, γ-aminobutyric acid; GFP, green fluorescent protein; hpf, hours post-fertilization; IB, insulin-like growth factors binding; IIS, insulin/ insulin-like growth factor signaling pathway; IGFBP7, insulin-like growth factor binding protein 7; IGFBPs, insulin-like growth factor binding proteins; IGFR, insulin-like growth factor receptor; ILPs, insulin-like peptides; Imp-L2, imaginal morphogenesis factor—late 2; InR, insulin receptor; MAPK, mitogen-activated protein kinases; NC, negative control; PBS, phosphate saline; PFA, paraformaldehyde; PI3K, phosphoinositide 3-kinase; PTTH, prothoracicotropic hormone; qRT-PCR, quantitative real time PCR; THs, thyroid hormones; WISH, whole mount in situ hybridization. "

    Full-text · Article · Jan 2016
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    • "This gene inhibits the insulin signaling pathway or those parallel to the signaling pathway of gene expression. In addition, miR- 71 is an effective regulator of the long-term survival and recovery of C. elegans from starvationinduced L1 diapause because of the functional relationship of the gene with the insulin/IGF-1 signaling (IIS) pathway (Michelangela et al., 2003; Sri Devi et al., 2009). We utilized TargetScan and mirWIP to predict the target genes of miR-71 in D. japonica. "
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    ABSTRACT: Planarians, which have a large population of stem cells called neoblasts, are molecularly tractable model systems used in the study of regeneration. However, planarians have strong resistance to hunger and have developed growth arrest strategies. For example, they can change their size and undergo growth regression during starvation periods. The results of the current study show that the microRNA, miR-71b, and the insulin/IGF-1 signaling pathway have important functions in the development of starvation-induced planarians. We demonstrate tissue-specific expression of miR-71b using in situ hybridization. By employing real-time polymerase chain reaction, we provide evidence that miR-71b is upregulated in starvation-induced planarians. Furthermore, we validate and verify the target genes of miR-71b.
    Preview · Article · Oct 2015 · Genetics and molecular research: GMR
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    • "Reductions in IGF-I activity with age are associated with reductions in SkM size and function. However, reduced signalling through the IIS pathway is also associated with increased lifespan and healthspan in model organisms (Clancy et al., 2001; Holzenberger et al., 2002; Barbieri et al., 2003; Tatar et al., 2003; Giannakou & Partridge, 2007; Piper et al., 2008; Selman et al., 2008; Vallejo et al., 2009; Kenyon, 2011; Selman et al., 2011). "
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    ABSTRACT: Advancing age is associated with a progressive loss of skeletal muscle (SkM) mass and function. Given the worldwide aging demographics, this is a major contributor to morbidity, escalating socio-economic costs and ultimately mortality. Previously, it has been established that a decrease in regenerative capacity in addition to SkM loss with age coincides with suppression of insulin/insulin-like growth factor signalling pathways. However, genetic or pharmacological modulations of these highly conserved pathways have been observed to significantly enhance life and healthspan in various species, including mammals. This therefore provides a controversial paradigm in which reduced regenerative capacity of skeletal muscle tissue with age potentially promotes longevity of the organism. This paradox will be assessed and considered in the light of the following: (i) the genetic knockout, overexpression and pharmacological models that induce lifespan extension (e.g. IRS-1/s6K KO, mTOR inhibition) versus the important role of these signalling pathways in SkM growth and adaptation; (ii) the role of the sirtuins (SIRTs) in longevity versus their emerging role in SkM regeneration and survival under catabolic stress; (iii) the role of dietary restriction and its impact on longevity versus skeletal muscle mass regulation; (iv) the crosstalk between cellular energy metabolism (AMPK/TSC2/SIRT1) and survival (FOXO) versus growth and repair of SkM (e.g. AMPK vs. mTOR); and (v) the impact of protein feeding in combination with dietary restriction will be discussed as a potential intervention to maintain SkM mass while increasing longevity and enabling healthy aging. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
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