Transcriptomic profiles of aging in purified human immune cells
Open accessAbstract
BACKGROUND: Transcriptomic studies hold great potential towards understanding the human aging process. Previous transcriptomic studies have identified many genes with age-associated expression levels; however, small samples sizes and mixed cell types often make these results difficult to interpret. RESULTS: Using transcriptomic profiles in CD14+ monocytes from 1,264 participants of the Multi-Ethnic Study of Atherosclerosis (aged 55-94 years), we identified 2,704 genes differentially expressed with chronological age (false discovery rate, FDR ≤ 0.001). We further identified six networks of co-expressed genes that included prominent genes from three pathways: protein synthesis (particularly mitochondrial ribosomal genes), oxidative phosphorylation, and autophagy, with expression patterns suggesting these pathways decline with age. Expression of several chromatin remodeler and transcriptional modifier genes strongly correlated with expression of oxidative phosphorylation and ribosomal protein synthesis genes. 17% of genes with age-associated expression harbored CpG sites whose degree of methylation significantly mediated the relationship between age and gene expression (p < 0.05). Lastly, 15 genes with age-associated expression were also associated (FDR ≤ 0.01) with pulse pressure independent of chronological age. Comparing transcriptomic profiles of CD14+ monocytes to CD4+ T cells from a subset (n = 423) of the population, we identified 30 age-associated (FDR < 0.01) genes in common, while larger sets of differentially expressed genes were unique to either T cells (188 genes) or monocytes (383 genes). At the pathway level, a decline in ribosomal protein synthesis machinery gene expression with age was detectable in both cell types. CONCLUSIONS: An overall decline in expression of ribosomal protein synthesis genes with age was detected in CD14+ monocytes and CD4+ T cells, demonstrating that some patterns of aging are likely shared between different cell types. Our findings also support cell-specific effects of age on gene expression, illustrating the importance of using purified cell samples for future transcriptomic studies. Longitudinal work is required to establish the relationship between identified age-associated genes/pathways and aging-related diseases.
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An analysis of age influence on the transcriptome in total CD4+ T cells identified relatively few gene expression differences with no striking pathway enrichment.
“An analysis of the influence of age on the transcriptome in total CD4+ T cells identified relatively few gene expression differences with no striking pathway enrichment”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Reynolds et al., 2015
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- Authors
- Reynolds, L. M., Ding, J., Taylor, J. R., Lohman, K., Soranzo, N., de la Fuente, A., Liu, T. F., Johnson, C., Barr, R. G., Register, T. C., Donohue, K. M., Talor, M. V., Cihakova, D., Gu, C., Divers, J., Siscovick, D., Burke, G., Post, W., Shea, S., Jacobs, D. R., Hoeschele, I., McCall, C. E., Kritchevsky, S. B., Herrington, D., Tracy, R. P., & Liu, Y.
- Affiliations
- Wake Forest University Health Sciences (US)
- Center for Advanced Studies Research and Development in Sardinia (IT)
- University of Washington (US)
- Columbia University (US)
- Johns Hopkins University (US)
- Washington University in St. Louis (US)
- New York Academy of Medicine (US)
- University of Minnesota (US)
- Virginia Tech (US)
- University of Vermont (US)
- Corresponding author
- Liu, Yongmei
- ORCID
- Reynolds, Lindsay M
- Ding, Jingzhong
- Taylor, Jackson R
- Soranzo, Nicola
- Johnson, Craig
- Barr, R Graham
- Register, Thomas C
- Talor, Monica V
- Gu, Charles
- Divers, Jasmin
- Siscovick, David
- Burke, Gregory
- Post, Wendy
- Shea, Steven
- Jacobs, David R
- McCall, Charles E
- Kritchevsky, Stephen B
- Herrington, David
- Tracy, Russell P
- Liu, Yongmei
- Venue
- BMC Genomics
- Published
- 2015-04-22
- Volume
- 16
- Issue
- 1
- Pages
- 333-333
- ISSN
- 1471-2164 (ISSN-L)
- PMC
- PMC4417516
- OpenAlex
- W2158033629
- Cited by
- 62
- References
- 81
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 10 · 2020: 9 · 2019: 6 · 2018: 8 · 2017: 12 · 2016: 1 · 2015: 2
- FWCI
- 3.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Genomics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
- Columbia Academic Commons (Columbia University)
- Funders
- Wake Forest University
- National Institutes of Health (5r01hl101250-05, KL2TR001874)
- National Institute on Aging (T32AG033534)
- National Heart, Lung, and Blood Institute (R01-HL-101250, RR-024156, R01HL077612)
- National Institute of General Medical Sciences (R01GM102497)
- National Institute of Allergy and Infectious Diseases (R01AI065791)
- National Center for Research Resources (UL1RR024156, UL1RR025005, RR024156, UL1-RR-024156 and UL1-RR-025005)
- National Center for Advancing Translational Sciences
- 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
- human aging, age-related gene expression, CD14+ monocytes, CD4+ T cells, ribosomal protein synthesis, oxidative phosphorylation, autophagy, CpG methylation, chromatin remodeling genes, pulse pressure
- MeSH terms
- Aged, Aged, 80 and over, Aging, Autophagy, Female, Humans, Male, Middle Aged, Monocytes, Oxidative Phosphorylation, Ribosomes, T-Lymphocytes, Protein Biosynthesis, CpG Islands, Lipopolysaccharide Receptors, DNA Methylation, Transcriptome
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