ArticleAutophagy2022
Spermidine overrides INSR (insulin receptor)-IGF1R (insulin-like growth factor 1 receptor)-mediated inhibition of autophagy in the aging heart.
Article in Autophagy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Established and emerging roles of lysosomal dysfunction in cardiac aging.Nature cardiovascular research · 2026Review
- Small-molecule IGF1R inhibitors extend healthspan in a mouse model.bioRxiv : the preprint server for biology · 2026Article
- Galangin 3-methyl ether alleviates mouse hypertrophic cardiomyopathy via targeting HDAC2 and subsequently inactivating the PI3K-AKT signaling pathway.Acta pharmacologica Sinica · 2026Article
- The Evolution of Gallic Acid in Aged White Tea and Its Potential Anti-Aging Mechanisms: An Integrated Study Combining Network Pharmacology and Computer Simulation.Food science & nutrition · 2025Article
- IGF1R deficiency mitigates acute lung injury by promoting anti-inflammatory transcriptional profiles.Respiratory research · 2025Article
- A Novel Research Paradigm for Sarcopenia of Limb Muscles: Lessons From the Perpetually Working Diaphragm's Anti-Aging Mechanisms.Journal of cachexia, sarcopenia and muscle · 2025Article
- Geroscience in heart failure: the search for therapeutic targets in the shared pathobiology of human aging and heart failure.The journal of cardiovascular aging · 2025Article
- ULK1 methylation promotes TGF-β1-induced endometrial fibrosis via the FOXP1/DNMT1 axis.The Kaohsiung journal of medical sciences · 2025Article
- Methamphetamine Increases Tubulo-Vesicular Areas While Dissipating Proteins from Vesicles Involved in Cell Clearance.International journal of molecular sciences · 2024Article
- Preliminary investigation into the genetic etiology of short stature in children through whole exon sequencing of the core family.Open life sciences · 2024Article
- Polyamines: their significance for maintaining health and contributing to diseases.Cell communication and signaling : CCS · 2023Review
- The role of autophagy in cardiovascular disease: Cross-interference of signaling pathways and underlying therapeutic targets.Frontiers in cardiovascular medicine · 2023Review
- Cardiac PI3K p110α attenuation delays aging and extends lifespan.Cell stress · 2022Article
- Targeting IGF1R signaling for brain aging and Alzheimer's disease.Aging pathobiology and therapeutics · 2022Article
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Authors and funding
4 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although attenuated IGF1R (insulin-like growth factor 1 receptor) signaling has long been viewed to promote longevity in model organisms, adverse effects on the heart have been the subject of major concern. We observed that IGF1R is overexpressed in cardiac tissues from patients with end-stage non-ischemic heart failure, coupled to the activation of the IGF1R downstream effector AKT/protein kinase B and inhibition of ULK1 (unc-51 like autophagy activating kinase 1). Transgenic overexpression of human IGF1R in cardiomyocytes from mice initially induces physiological cardiac hypertrophy and superior function, but later in life confers a negative impact on cardiac health, causing macroautophagy/autophagy inhibition as well as impaired oxidative phosphorylation, thus reducing life expectancy. Treatment with the autophagy inducer and caloric restriction mimetic spermidine ameliorates most of these IGF1R-induced cardiotoxic effects in vivo. Moreover, inhibition of IGF1R signaling by means of a dominant-negative phosphoinositide 3-kinase (PI3K) mutant induces cardioprotective autophagy, restores myocardial bioenergetics and improves late-life survival. Hence, our results demonstrate that IGF1R exerts a dual biphasic impact on cardiac health, and that autophagy mediates the late-life geroprotective effects of IGF1R inhibition in the heart.
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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.