ArticleAging2016
Gerosuppression by pan-mTOR inhibitors.
Article in Aging, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 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
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Targeting cellular senescence with Traditional Chinese Medicine: advances in neurodegenerative disorder treatment.Frontiers in neurology · 2026Pooled it
- Epigenetic program of ontogenesis and hyperfunction theory: reinterpreting the mechanisms of aging.Frontiers in aging · 2026Article
- Regulation of ribosomal gene expression and senescence by a PML-mTOR-RONIN nuclear complex in triple-negative breast cancer.Oncogene · 2025Article
- Cellular senescence in Alzheimer's disease: from physiology to pathology.Translational neurodegeneration · 2024Review
- Article
- In vitro heterochronic parabiosis identifies pigment epithelium-derived factor as a systemic mediator of rejuvenation by young blood.bioRxiv : the preprint server for biology · 2024Article
- Counteracting Immunosenescence-Which Therapeutic Strategies Are Promising?Biomolecules · 2023Review
- Targeting mTOR for Anti-Aging and Anti-Cancer Therapy.Molecules (Basel, Switzerland) · 2023Review
- Article
- Oral Lichen Planus and Oral Squamous Cell Carcinoma share key oncogenic signatures.Scientific reports · 2022Article
- Inhibition of mTOR in bovine monocyte derived macrophages and dendritic cells provides a potential mechanism for postpartum immune dysfunction in dairy cows.Scientific reports · 2022Article
- Cell senescence, rapamycin and hyperfunction theory of aging.Cell cycle (Georgetown, Tex.) · 2022Review
- The hyperfunction theory: An emerging paradigm for the biology of aging.Ageing research reviews · 2022Review
- Discovery of small molecule mechanistic target of rapamycin inhibitors as anti-aging and anti-cancer therapeutics.Frontiers in aging neuroscience · 2022Article
- Recent Advances in Dual PI3K/mTOR Inhibitors for Tumour Treatment.Frontiers in pharmacology · 2022Review
- Article
- Anti-aging: senolytics or gerostatics (unconventional view).Oncotarget · 2021Review
- Mycobacterium tuberculosis PE_PGRS20 and PE_PGRS47 Proteins Inhibit Autophagy by Interaction with Rab1A.mSphere · 2021Article
- The goal of geroscience is life extension.Oncotarget · 2021Article
- Translational Control during Cellular Senescence.Molecular and cellular biology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rapamycin slows organismal aging and delays age-related diseases, extending lifespan in numerous species. In cells, rapamycin and other rapalogs such as everolimus suppress geroconversion from quiescence to senescence. Rapamycin inhibits some, but not all, activities of mTOR. Recently we and others demonstrated that pan-mTOR inhibitors, known also as dual mTORC1/C2 inhibitors, suppress senescent phenotype. As a continuation of these studies, here we investigated in detail a panel of pan-mTOR inhibitors, to determine their optimal gerosuppressive concentrations. During geroconversion, cells become hypertrophic and flat, accumulate lysosomes (SA-beta-Gal staining) and lipids (Oil Red staining) and lose their re-proliferative potential (RPP). We determined optimal gerosuppressive concentrations: Torin1 (30 nM), Torin 2 (30 nM), AZD8055 (100 nM), PP242 (300 nM), both KU-006379 and GSK1059615 (1000 nM). These agents decreased senescence-associated hypertrophy with IC50s: 20, 18, 15, 200 and 400 nM, respectively. Preservation of RPP by pan-mTOR inhibitors was associated with inhibition of the pS6K/pS6 axis. Inhibition of rapamycin-insensitive functions of mTOR further contributed to anti-hypertrophic and cytostatic effects. Torin 1 and PP242 were more "rapamycin-like" than Torin 2 and AZD8055. Pan-mTOR inhibitors were superior to rapamycin in suppressing hypertrophy, senescent morphology, Oil Red O staining and in increasing so-called "chronological life span (CLS)". We suggest that, at doses lower than anti-cancer concentrations, pan-mTOR inhibitors can be developed as anti-aging drugs.
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What Socratic holds
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 Socratic graph.