ArticleProceedings of the National Academy of Sciences of the United States of America2018
Effects of rapamycin on growth hormone receptor knockout mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Rapamycin, Not Metformin, Mirrors Dietary Restriction-Driven Lifespan Extension in Vertebrates: A Meta-Analysis.Aging cell · 2025Pooled it
- Traditional Chinese Medicine Formulas in Delaying Aging: From Theoretical Foundations to Molecular Mechanisms and Translational Perspectives.Journal of cellular and molecular medicine · 2026Review
- Midlife Growth Hormone Receptor Ablation Extends Healthy Lifespan and Induces Sex-Specific Hepatic Transcriptional Changes at Single-Cell Resolution.Aging cell · 2026Article
- Bench to bedside: is rapamycin headed for the docTOR?GeroScience · 2026Review
- Enhancing immunity during ageing by targeting interactions within the tissue environment.Nature reviews. Drug discovery · 2025Review
- GHR disruption in mature adult mice alters xenobiotic metabolism gene expression in the liver.Pituitary · 2023Article
- Targeting the biology of aging with mTOR inhibitors.Nature aging · 2023Review
- Disruption of Growth Hormone Receptor in Adipocytes Improves Insulin Sensitivity and Lifespan in Mice.Endocrinology · 2022Article
- Rapamycin treatment during development extends life span and health span of male mice andScience advances · 2022Article
- Activation of Rictor/mTORC2 signaling acts as a pivotal strategy to protect against sensorineural hearing loss.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Exosome Biogenesis and Lysosome Function Determine Podocyte Exosome Release and Glomerular Inflammatory Response during Hyperhomocysteinemia.The American journal of pathology · 2022Article
- Growth hormone receptor gene disruption in mature-adult mice improves male insulin sensitivity and extends female lifespan.Aging cell · 2021Article
- Therapeutic mTOR blockade in systemic autoimmunity: Implications for antiviral immunity and extension of lifespan.Autoimmunity reviews · 2021Review
- Effects of Rapamycin on Insulin Brain Endothelial Cell Binding and Blood-Brain Barrier Transport.Medical sciences (Basel, Switzerland) · 2021Article
- Regulation and metabolic functions of mTORC1 and mTORC2.Physiological reviews · 2021Review
- Extending lifespan by modulating the growth hormone/insulin-like growth factor-1 axis: coming of age.Pituitary · 2021Review
- Effect of rapamycin on aging and age-related diseases-past and future.GeroScience · 2021Review
- Decline in biological resilience as key manifestation of aging: Potential mechanisms and role in health and longevity.Mechanisms of ageing and development · 2021Review
- Growth hormone and aging.Reviews in endocrine & metabolic disorders · 2021Review
- Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
It is well documented that inhibition of mTORC1 (defined by Raptor), a complex of mechanistic target of rapamycin (mTOR), extends life span, but less is known about the mechanisms by which mTORC2 (defined by Rictor) impacts longevity. Here, rapamycin (an inhibitor of mTOR) was used in GHR-KO (growth hormone receptor knockout) mice, which have suppressed mTORC1 and up-regulated mTORC2 signaling, to determine the effect of concurrently decreased mTORC1 and mTORC2 signaling on life span. We found that rapamycin extended life span in control normal (N) mice, whereas it had the opposite effect in GHR-KO mice. In the rapamycin-treated GHR-KO mice, mTORC2 signaling was reduced without further inhibition of mTORC1 in the liver, muscle, and s.c. fat. Glucose and lipid homeostasis were impaired, and old GHR-KO mice treated with rapamycin lost functional immune cells and had increased inflammation. In GHR-KO MEF cells, knockdown of Rictor, but not Raptor, decreased mTORC2 signaling. We conclude that drastic reduction of mTORC2 plays important roles in impaired longevity in GHR-KO mice via disruption of whole-body homeostasis.
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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.