Age-Related Gene Expression Signature in Rats Demonstrate Early, Late, and Linear Transcriptional Changes from Multiple Tissues
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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.
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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 measuredPresence 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 measuredComparison 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.”
From Senescence atlas reveals an aged-like inflamed niche that blunts muscle regeneration (2023) · cites this paper as [38]
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- 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.
- ORCID
- 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
- gold
- doi.org
- Licence
- 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
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