Meta-analysis of age-related gene expression profiles identifies common signatures of aging
Open accessAbstract
Motivation: Numerous microarray studies of aging have been conducted, yet given the noisy nature of gene expression changes with age, elucidating the transcriptional features of aging and how these relate to physiological, biochemical and pathological changes remains a critical problem. Results: We performed a meta-analysis of age-related gene expression profiles using 27 datasets from mice, rats and humans. Our results reveal several common signatures of aging, including 56 genes consistently overexpressed with age, the most significant of which was APOD, and 17 genes underexpressed with age. We characterized the biological processes associated with these signatures and found that age-related gene expression changes most notably involve an overexpression of inflammation and immune response genes and of genes associated with the lysosome. An underexpression of collagen genes and of genes associated with energy metabolism, particularly mitochondrial genes, as well as alterations in the expression of genes related to apoptosis, cell cycle and cellular senescence biomarkers, were also observed. By employing a new method that emphasizes sensitivity, our work further reveals previously unknown transcriptional changes with age in many genes, processes and functions. We suggest these molecular signatures reflect a combination of degenerative processes but also transcriptional responses to the process of aging. Overall, our results help to understand how transcriptional changes relate to the process of aging and could serve as targets for future studies. Availability: http://genomics.senescence.info/uarrays/signatures.html Contact: jp@senescence.info Supplementary information: Supplementary data are available at Bioinformatics online.
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These SASP cells showed enrichment of previously published gene sets indicative of human and cellular aging.
“as well as enrichment of previously published gene sets indicative of human49 and cellular aging50 (Table 2).”
From A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues (2022) · cites this paper as [49]
NF-κB pathway activation is a recognized transcriptional signature driving chronic inflammation in aged skin, muscle, bone and nervous system.
“Activation of the NF-κB pathway is a known transcriptional signature that mediates chronic inflammation in aged skin, skeletal muscle, bone and nervous system163, although the direct effects of NF-κB activation on stem function in these tissues is still under investigation.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [163]
Zahn et al. reported aging-driven upregulation of ribosomal genes in human brain and muscle tissues and later upregulation in mouse neuronal tissues but downregulation in non-neuronal tissues.
“Zahn et al. reported an aging-driven upregulation of ribosomal genes in human brain and muscle tissues 37 and, in a later study, reported an aging-driven upregulation of ribosomal genes in mouse neuronal tissues 6 but a downregulation of the same genes in non-neuronal tissues 6 .”
From Single-cell transcriptomic profiling of the aging mouse brain (2019) · cites this paper as [6]
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“These findings are similar to those of a meta-analysis of agerelated gene expression profiles using datasets from mice, rats, and humans (de Magalhaes et al., 2009).”
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- Authors
- de Magalhães, J. P., Curado, J., & Church, G. M.
- Affiliations
- 1 Department of Genetics, Harvard Medical School, Boston, MA 02115, USA and 2Escola Superior de Biotecnologia, 4200 Porto, Portugal
- Harvard University (US)
- ORCID
- Church, George M.
- Venue
- Bioinformatics
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-02-02
- Volume
- 25
- Issue
- 7
- Pages
- 875-881
- ISSN
- 1367-4803 (ISSN-L)
- 1367-4811
- PMC
- PMC2732303
- OpenAlex
- W2108700752
- Cited by
- 737
- References
- 50
- Citations by year
- 2026: 24 · 2025: 30 · 2024: 39 · 2023: 57 · 2022: 47 · 2021: 60 · 2020: 57 · 2019: 49 · 2018: 50 · 2017: 45 · 2016: 38 · 2015: 56 · 2014: 34 · 2013: 49 · 2012: 40
- FWCI
- 3.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Bioinformatics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- 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 › Gene expression and cancer classification
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- aging, age-related gene expression, gene expression signatures, apolipoprotein D, inflammation, immune response genes, lysosomes, collagen genes, energy metabolism, mitochondrial genes, apoptosis, cell cycle, cellular senescence, meta-analysis of microarray data
- MeSH terms
- Aging, Animals, Humans, Transcription, Genetic, Gene Expression Profiling, Mice, Rats
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