Cited by 175Genetics, Aging, and Longevity in Model OrganismsSingle-cell and spatial transcriptomicsGenomics and Chromatin Dynamics

Age-Related Gene Expression Signature in Rats Demonstrate Early, Late, and Linear Transcriptional Changes from Multiple Tissues

Open access
Shavlakadze, Tea, Morris, Melody, Fang, Jian, Wang, Sharon X., Zhu, Jiang, Zhou, Weihua, Tse, Herman W., Mondragon-Gonzalez, Ricardo +2 more·2019·Cell Reports

Published version of a preprint

Abstract

To understand the changes in gene expression that occur as a result of age, which might create a permissive or causal environment for age-related diseases, we produce a multi-time point age-related gene expression signature (AGES) from liver, kidney, skeletal muscle, and hippocampus of rats, comparing 6-, 9-, 12-, 18-, 21-, 24-, and 27-month-old animals. We focus on genes that changed in one direction throughout the lifespan of the animal, either early in life (early logistic changes), at mid-age (mid-logistic), late in life (late-logistic), or linearly, throughout the lifespan of the animal. The pathways perturbed because of chronological age demonstrate organ-specific and more-global effects of aging and point to mechanisms that could potentially be counter-regulated pharmacologically to treat age-associated diseases. A small number of genes are regulated by aging in the same manner in every tissue, suggesting they may be more-universal markers of aging.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.celrep.2019.08.043

Cites

43 of 43 references verified0 citation errors · 0 not checkable

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.

A few free checks a day · papers already verified open instantly · results are public

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?

  • We detected upregulation of complement, interferon and TNF/NF-κB pathways in senescent cells, which are robustly activated with ageing across vertebrate tissues, including humans.

    “We detected upregulation of complement, interferon and TNF/NF-κB pathways in senescent cells, which are robustly activated with ageing across vertebrate tissues, including humans36–38.”

    From Senescence atlas reveals an aged-like inflamed niche that blunts muscle regeneration (2023) · cites this paper as [38]

    The pathway analysis reports age-related upregulation of complement and interferon pathways in four rat tissues, and the Discussion (p. 18) reports increased TNF-alpha-induced genes in those tissues. The paper also notes related findings in human kidney and for complement in humans (pp. 16, 18), but it does not establish robust activation of all three pathways across vertebrate tissues, including human tissues generally; its NF-κB evidence is an enriched motif in aging rat liver (p. 12). (LLM, conf=0.85)

    Experimental — accuracy not yet measured
  • Presence of a type I IFN signature in brain cells, in particular microglia, is increasingly associated with ageing and neurodegenerative disease in various species.

    “The presence of a type I IFN signature in brain cells, in particular in microglia, is increasingly being associated with ageing and neurodegenerative disease in various species13,15,39,44–50.”

    From cGAS–STING drives ageing-related inflammation and neurodegeneration (2023) · cites this paper as [45]

    The pathway-analysis passage (Figures 4A–B; page not specified) reports that interferon-alpha and -gamma response pathways increased with age in rat hippocampus. The brain discussion (near p. 16) suggests age-related glial activation, but the paper does not establish a type I IFN signature specifically in microglia or link that signature to neurodegenerative disease across species. (LLM, conf=0.85)

    Experimental — accuracy not yet measured
  • Comparison of transcriptomes of ageing tissues from various species (including humans) with those of Sen cells from injured young muscles found an increase in inflammatory pathways (interferon, complement and cytokine and TNF/NF-κB signalling), consistent with previously published datasets.

    “We next compared the transcriptomes of ageing tissues from various species (including humans) with those of Sen cells from injured young muscles, and found an increase in inflammatory pathways (interferon, complement and cytokine and TNF/NF-κB signalling) (Fig. 5b), consistent with previously published datasets36–38.”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Shavlakadze, T., Morris, M., Fang, J., Wang, S. X., Zhu, J., Zhou, W., Tse, H. W., Mondragon-Gonzalez, R., Roma, G., & Glass, D. J.
Affiliations
Novartis Institutes for BioMedical Research (CH)
Corresponding author
  • Shavlakadze, Tea
  • Glass, David J.
Venue
Cell Reports
Publisher
Elsevier BV
Published
2019-09
Volume
28
Issue
12
Pages
3263-3273.e3
ISSN
2211-1247 (ISSN-L)
OpenAlex
W2974147992
Cited by
170
References
43
Citations by year
2026: 17 · 2025: 11 · 2024: 33 · 2023: 34 · 2022: 26 · 2021: 29 · 2020: 18 · 2019: 2
FWCI
6.83
Type
journal article
Language
en
Open access
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Novartis
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
aging, gene expression signatures, age-related gene expression, multi-tissue transcriptomics, liver, kidney, skeletal muscle, hippocampus, age-related diseases, age markers, organ-specific aging, rats

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