ArticleAging cell2015
Suppression of IGF-I signals in neural stem cells enhances neurogenesis and olfactory function during aging.
Article in Aging cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 83 citations in OpenAlex.
- Effects of Moxibustion on the Levels of Insulin-Like Growth Factor 1: A Pilot Study.Cell transplantation · 2018Trial
- Insulin-like growth factor receptor signaling in physiology and disease.Signal transduction and targeted therapy · 2026Review
- Lipidomic profiling reveals age-dependent changes in plasma membrane lipids that affect neural stem cell aging.Science advances · 2026Article
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- Neural stem cell secretome: a secret key to unlocking the power of regeneration in the adult and aging brain.Aging brain · 2025Article
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- Underlying Mechanisms and Treatment of Cellular Senescence-Induced Biological Barrier Interruption and Related Diseases.Aging and disease · 2024Review
- Review
- Implications of Hypothalamic Neural Stem Cells on Aging and Obesity-Associated Cardiovascular Diseases.Cells · 2023Review
- Redox-dependent Igfbp2 signaling controls Brca1 DNA damage response to govern neural stem cell fate.Nature communications · 2023Article
- IGF-1 receptor regulates upward firing rate homeostasis via the mitochondrial calcium uniporter.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Systems genetics in the rat HXB/BXH family identifies Tti2 as a pleiotropic quantitative trait gene for adult hippocampal neurogenesis and serum glucose.PLoS genetics · 2022Article
- Mini-batch optimization enables training of ODE models on large-scale datasets.Nature communications · 2022Article
- Bioenergetic Impairment in the Neuro-Glia-Vascular Unit: An Emerging Physiopathology during Aging.Aging and disease · 2021Review
- Olfactory impairment in men and mice related to aging and amyloid-induced pathology.Pflugers Archiv : European journal of physiology · 2021Review
- Oncogenic State and Cell Identity Combinatorially Dictate the Susceptibility of Cells within Glioma Development Hierarchy to IGF1R Targeting.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- Aging and Rejuvenation of Neural Stem Cells and Their Niches.Cell stem cell · 2020Review
- Rejuvenating subventricular zone neurogenesis in the aging brain.Current opinion in pharmacology · 2020Review
- Systemic GDF11 stimulates the secretion of adiponectin and induces a calorie restriction-like phenotype in aged mice.Aging cell · 2020Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Downregulation of insulin-like growth factor (IGF) pathways prolongs lifespan in various species, including mammals. Still, the cellular mechanisms by which IGF signaling controls the aging trajectory of individual organs are largely unknown. Here, we asked whether suppression of IGF-I receptor (IGF-1R) in adult stem cells preserves long-term cell replacement, and whether this may prevent age-related functional decline in a regenerating tissue. Using neurogenesis as a paradigm, we showed that conditional knockout of IGF-1R specifically in adult neural stem cells (NSC) maintained youthful characteristics of olfactory bulb neurogenesis within an aging brain. We found that blocking IGF-I signaling in neural precursors increased cumulative neuroblast production and enhanced neuronal integration into the olfactory bulb. This in turn resulted in neuro-anatomical changes that improved olfactory function. Interestingly, mutants also displayed long-term alterations in energy metabolism, possibly related to IGF-1R deletion in NSCs throughout lifespan. We explored Akt and ERK signaling cascades and revealed differential regulation downstream of IGF-1R, with Akt phosphorylation preferentially decreased in IGF-1R(-/-) NSCs within the niche, and ERK pathway downregulated in differentiated neurons of the OB. These challenging experimental results were sustained by data from mathematical modeling, predicting that diminished stimulation of growth is indeed optimal for tissue aging. Thus, inhibiting growth and longevity gene IGF-1R in adult NSCs induced a gain-of-function phenotype during aging, marked by optimized management of cell renewal, and enhanced olfactory sensory function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.