Transposon-triggered innate immune response confers cancer resistance to the blind mole rat
Open accessAbstract
Blind mole rats (BMRs) are small rodents, characterized by an exceptionally long lifespan (>21 years) and resistance to both spontaneous and induced tumorigenesis. Here we report that cancer resistance in the BMR is mediated by retrotransposable elements (RTEs). Cells and tissues of BMRs express very low levels of DNA methyltransferase 1. Following cell hyperplasia, the BMR genome DNA loses methylation, resulting in the activation of RTEs. Upregulated RTEs form cytoplasmic RNA-DNA hybrids, which activate the cGAS-STING pathway to induce cell death. Although this mechanism is enhanced in the BMR, we show that it functions in mice and humans. We propose that RTEs were co-opted to serve as tumor suppressors that monitor cell proliferation and are activated in premalignant cells to trigger cell death via activation of the innate immune response. Activation of RTEs is a double-edged sword, serving as a tumor suppressor but contributing to aging in late life via the induction of sterile inflammation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Intracellular cues such as retrotransposable elements (e.g., LINE-1), cytosolic mitochondrial DNA, and circular DNA can activate cGAS-STING and trigger pro-inflammatory genes weeks or months after senescence induction.
“These include retrotransposable elements (for example, LINE-1), cytosolic mitochondrial DNA, or circular DNA—all of which can activate the cytosolic DNA-sensing (cGAS)-STING pathway, triggering the expression of pro-inflammatory genes79–81.”
From Cellular senescence and senolytics: the path to the clinic (2022) · cites this paper as [80]
The Results section (‘RTEs form Cytoplasmic RNA/DNA Hybrids and induce cGAS-STING’; page not provided) links LINE-1 and other retrotransposons to cGAS-STING activation and IFNB1/SASP gene expression in blind mole rat cells. The cited paper does not establish the same pathway for cytosolic mitochondrial DNA or circular DNA, or a weeks-to-months delay after senescence induction. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe SASP is dynamic, changes over time, and varies with the type of senescent cell and how senescence was induced.
“The SASP of senescent cells is not static; it can change over time78–80 and varies depending on the type of cells that became senescent and how senescence was induced16,44,59,60,81.”
From Cellular senescence and senolytics: the path to the clinic (2022) · cites this paper as [80]
The citation is attached to the claim that SASP varies by senescent cell type and mode of induction. The Results section and Extended Data Fig. 1 report SASP activation in over-proliferating blind mole rat cells, but do not compare SASP across senescent cell types or induction methods. I searched the indexed copy for those comparisons; no passage establishes the attributed variation. (LLM, conf=0.70)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 78 · Cited by 99
- Authors
- Zhao, Y., Oreskovic, E., Zhang, Q., Lu, Q., Gilman, A., Lin, Y. S., He, J., Zheng, Z., Lu, J. Y., Lee, J., Ke, Z., Ablaeva, J., Sweet, M. J., Horvath, S., Zhang, Z., Nevo, E., Seluanov, A., & Gorbunova, V.
- Affiliations
- University of Rochester (US)
- Albert Einstein College of Medicine (US)
- The University of Queensland (AU)
- University of California, Los Angeles (US)
- University of Haifa (IL)
- University of Rochester Medicine (US)
- Corresponding author
- Seluanov, Andrei
- Gorbunova, Vera
- ORCID
- Venue
- Nature Immunology
- Published
- 2021-09-23
- Volume
- 22
- Issue
- 10
- Pages
- 1219-1230
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC8488014
- OpenAlex
- W3200783369
- Cited by
- 99
- References
- 78
- Citations by year
- 2026: 20 · 2025: 25 · 2024: 14 · 2023: 16 · 2022: 21 · 2021: 3
- FWCI
- 4.83
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | Office of Extramural Research, National Institutes of Health (AG047200)
- U.S. Department of Health & Human Services | National Institutes of Health (AG051449, AG047200)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- blind mole rat, tumor resistance, transposable elements, DNA methylation, DNMT1, RNA-DNA hybrids, cGAS-STING pathway, innate immune response, tumor suppression, sterile inflammation, aging, cell death
- MeSH terms
- Animals, Cells, Cultured, DNA, DNA Transposable Elements, HeLa Cells, Humans, Immunity, Innate, Mice, Inbred C57BL, Mice, Nude, Neoplasms, Signal Transduction, Mole Rats, Cell Line, Tumor, Cell Proliferation, Mice, Rats, Carcinogenesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
