ArticleAging cell2017
Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism.
Article in Aging cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 203 papers, 1 of them a synthesis 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.
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Who cites it
203 citing papers in PubMed, 1 synthesis or guideline pooled it, 340 citations in OpenAlex.
- Pooled it
- Article
- Cellular senescence and regulated cell death in cancer: mechanisms, cross-regulatory networks and therapeutic implications.Journal of hematology & oncology · 2026Review
- The role of senescence in kidney ageing, injury and fibrosis.Nature reviews. Nephrology · 2026Review
- The vicious cycle of SASP and inflammaging promotes aging and age-related diseases.Communications biology · 2026Review
- Closing the gap in aging science: unlocking the potential of nanoparticles in senescence therapy.Biogerontology · 2026Review
- Article
- Pharmacological targeting of the senescence-associated secretory phenotype in atherosclerosis: therapeutic potential of senolytics and senomorphics.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- NRF2 Deletion Results in Mobility Impairment in A53TSyn Model of Synucleinopathy.Antioxidants (Basel, Switzerland) · 2026Article
- Aging and cancer: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Skin aging: mechanisms, evaluation, and rejuvenation.The EMBO journal · 2026Review
- Flavonoid compounds from Shenrong Guben Huanshao Pill alleviates senescence-associated mitochondrial dysfunction through NDUFV2 and LDHB mediated metabolic reprogramming.Journal of pharmaceutical analysis · 2026Article
- Review
- Viral Mimicry of Alzheimer's Disease: Innate Sensing of Self-Nucleic Acids as a Driver of Glial Senescence.Journal of molecular neuroscience : MN · 2026Review
- Chronic Kidney Disease and Cellular Senescence.International journal of molecular sciences · 2026Review
- Homoharringtonine exhibits senotherapeutic activity that mitigates diet- and age-associated obesity and insulin resistance and extends lifespan in mice.Nature communications · 2026Article
- Improving surgical treatments for hepatocellular carcinoma.Nature reviews. Gastroenterology & hepatology · 2026Review
- A Review of Ionizing Radiation-Induced Senescence of Bone Marrow Mesenchymal Stem/Stromal Cells: Mechanisms and Therapeutic Strategies.Current issues in molecular biology · 2026Review
- Kidney Disease as a Driver of Immunosenescence: Mechanisms and Potential Interventions.Journal of the American Society of Nephrology : JASN · 2026Review
- Therapy-induced senescence in breast cancer and cardiovascular disease: a double-edged biological process.Frontiers in cardiovascular medicine · 2026Review
143 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
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Senescent cells contribute to age-related pathology and loss of function, and their selective removal improves physiological function and extends longevity. Rapamycin, an inhibitor of mTOR, inhibits cell senescence in vitro and increases longevity in several species. Nrf2 levels have been shown to decrease with aging and silencing Nrf2 gene induces premature senescence. Therefore, we explored whether Nrf2 is involved in the mechanism by which rapamycin delays cell senescence. In wild-type (WT) mouse fibroblasts, rapamycin increased the levels of Nrf2, and this correlates with the activation of autophagy and a reduction in the induction of cell senescence, as measured by SA-β-galactosidase (β-gal) staining, senescence-associated secretory phenotype (SASP), and p16 and p21 molecular markers. In Nrf2KO fibroblasts, however, rapamycin still decreased β-gal staining and the SASP, but rapamycin did not activate the autophagy pathway or decrease p16 and p21 levels. These observations were further confirmed in vivo using Nrf2KO mice, where rapamycin treatment led to a decrease in β-gal staining and pro-inflammatory cytokines in serum and fat tissue; however, p16 levels were not significantly decreased in fat tissue. Consistent with literature demonstrating that the Stat3 pathway is linked to the production of SASP, we found that rapamycin decreased activation of the Stat3 pathway in cells or tissue samples from both WT and Nrf2KO mice. Our data thus suggest that cell senescence is a complex process that involves at least two arms, and rapamycin uses Nrf2 to regulate cell cycle arrest, but not the production of SASP.
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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.