ArticleAging cell2015
Chronic mTOR inhibition in mice with rapamycin alters T, B, myeloid, and innate lymphoid cells and gut flora and prolongs life of immune-deficient mice.
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 86 papers, 2 of them syntheses that pooled it.
What it found
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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.
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
86 citing papers in PubMed, 2 syntheses or guidelines pooled it, 121 citations in OpenAlex.
- Rapamycin, Not Metformin, Mirrors Dietary Restriction-Driven Lifespan Extension in Vertebrates: A Meta-Analysis.Aging cell · 2025Pooled it
- Rapamycin not dietary restriction improves resilience against pathogens: a meta-analysis.GeroScience · 2023Pooled it
- Rapamycin Prevents Surgery-Induced Immune Dysfunction in Patients with Bladder Cancer.Cancer immunology research · 2019Trial
- A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort: Immunological, physical performance, and cognitive effects.Experimental gerontology · 2018Trial
- The gut microbiome and allograft outcomes: implications for heart transplantation.The Journal of clinical investigation · 2026Review
- Short-term mTOR inhibition by rapamycin improves cardiac and endothelial function in older men: a proof-of concept pilot study.GeroScience · 2026Article
- Organelle resilience as a comparative blueprint for longevity.EMBO molecular medicine · 2026Review
- Therapy-induced senescent cancer cells as bidirectional regulators of antitumor immunity and resistance in the tumor microenvironment.Cell death & disease · 2026Review
- Aging modulation of the immune system and immunotherapy efficacy in cancer.Frontiers in immunology · 2026Review
- Long-term rapamycin treatment suppresses IL-17-producing gamma delta T cells and blunts neuroinflammation in aging.PloS one · 2026Article
- Anti-PD-L2 immunotherapy is efficacious against melanoma in aged hosts through IL-17 and IFNγ signalling.Nature communications · 2025Article
- Rewinding the Clock: Emerging Pharmacological Strategies for Human Anti-Aging Therapy.International journal of molecular sciences · 2025Review
- Immunoregulatory mechanisms in the aging microenvironment: Targeting the senescence-associated secretory phenotype for cancer immunotherapy.Acta pharmaceutica Sinica. B · 2025Review
- Postbiotics: A Promising Approach to Combat Age-Related Diseases.Life (Basel, Switzerland) · 2025Review
- Rapamycin immunomodulation utilizes time-dependent alterations of lymph node architecture, leukocyte trafficking, and gut microbiome.JCI insight · 2025Article
- Review
- Effects of Long-term low-dose intermittent rapamycin administration on glucose metabolism and immune system of SAMP8 and SAMR1 mice.Frontiers in immunology · 2025Article
- Adhesive lipophilic gels delivering rapamycin prevent oral leukoplakia from malignant transformation.Materials today. Bio · 2024Article
- Targeting Cell Senescence and Senolytics: Novel Interventions for Age-Related Endocrine Dysfunction.Endocrine reviews · 2024Review
- mTOR and SGLT-2 Inhibitors: Their Synergistic Effect on Age-Related Processes.International journal of molecular sciences · 2024Review
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
The mammalian (mechanistic) target of rapamycin (mTOR) regulates critical immune processes that remain incompletely defined. Interest in mTOR inhibitor drugs is heightened by recent demonstrations that the mTOR inhibitor rapamycin extends lifespan and healthspan in mice. Rapamycin or related analogues (rapalogues) also mitigate age-related debilities including increasing antigen-specific immunity, improving vaccine responses in elderly humans, and treating cancers and autoimmunity, suggesting important new clinical applications. Nonetheless, immune toxicity concerns for long-term mTOR inhibition, particularly immunosuppression, persist. Although mTOR is pivotal to fundamental, important immune pathways, little is reported on immune effects of mTOR inhibition in lifespan or healthspan extension, or with chronic mTOR inhibitor use. We comprehensively analyzed immune effects of rapamycin as used in lifespan extension studies. Gene expression profiling found many and novel changes in genes affecting differentiation, function, homeostasis, exhaustion, cell death, and inflammation in distinct T- and B-lymphocyte and myeloid cell subpopulations. Immune functions relevant to aging and inflammation, and to cancer and infections, and innate lymphoid cell effects were validated in vitro and in vivo. Rapamycin markedly prolonged lifespan and healthspan in cancer- and infection-prone mice supporting disease mitigation as a mechanism for mTOR suppression-mediated longevity extension. It modestly altered gut metagenomes, and some metagenomic effects were linked to immune outcomes. Our data show novel mTOR inhibitor immune effects meriting further studies in relation to longevity and healthspan extension.
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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.