Circulating Proteomic Signatures of Chronological Age
Open accessAbstract
To elucidate the proteomic features of aging in plasma, the subproteome targeted by the SOMAscan assay was profiled in blood samples from 202 females from the TwinsUK cohort. Findings were replicated in 677 independent individuals from the AddNeuroMed, Alzheimer's Research UK, and Dementia Case Registry cohorts. Results were further validated using RNAseq data from whole blood in TwinsUK and the most significant proteins were tested for association with aging-related phenotypes after adjustment for age. Eleven proteins were associated with chronological age and were replicated at protein level in an independent population. These were further investigated at gene expression level in 384 females from the TwinsUK cohort. The two most strongly associated proteins were chordin-like protein 1 (meta-analysis β [SE] = 0.013 [0.001], p = 3.66 × 10(-46)) and pleiotrophin (0.012 [0.005], p = 3.88 × 10(-41)). Chordin-like protein 1 was also significantly correlated with birthweight (0.06 [0.02], p = 0.005) and with the individual Framingham 10-years cardiovascular risk scores in TwinsUK (0.71 [0.18], p = 9.9 × 10(-5)). Pleiotrophin is a secreted growth factor with a plethora of functions in multiple tissues and known to be a marker for cardiovascular risk and osteoporosis. Our study highlights the importance of proteomics to identify some molecular mechanisms involved in human health and aging.
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Studies using multiple proteomic technologies have shown that thousands of proteins change with age in human plasma and cerebrospinal fluid.
“Studies using multiple proteomic technologies have shown that thousands of proteins change with age in human plasma91–93 and cerebrospinal fluid94, which has recently led to the development of multiple proteomic ageing clocks.”
From Measuring biological age using omics data (2022) · cites this paper as [91]
Baird et al. and Menni et al. developed the first ageing clock models based on the SomaLogic aptamer-based proteomic platform using human cerebrospinal fluid and plasma samples, respectively, although associations with any ageing phenotypes or organ function were not examined.
“Pioneering studies by Baird et al.94 and Menni et al.91 developed the first ageing clock models based on the SomaLogic aptamer-based proteomic platform using human cerebrospinal fluid and plasma samples, respectively, although associations with any ageing phenotypes or organ function were not examined.”
From Measuring biological age using omics data (2022) · cites this paper as [91]
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Self-citation
- Authors
- Menni, C., Kiddle, S. J., Mangino, M., Viñuela, A., Psatha, M., Steves, C., Sattlecker, M., Buil, A., Newhouse, S., Nelson, S., Williams, S., Voyle, N., Soininen, H., Kloszewska, I., Mecocci, P., Tsolaki, M., Vellas, B., Lovestone, S., Spector, T. D., Dobson, R., & Valdes, A. M.
- Affiliations
- King's College London (GB)
- University of Geneva (CH)
- SomaLogic (United States) (US)
- University of Eastern Finland (FI)
- University of Perugia (IT)
- Aristotle University of Thessaloniki (GR)
- Inserm (FR)
- University of Oxford (GB)
- University of Nottingham (GB)
- Corresponding author
- Menni, Cristina
- Kiddle, Steven J.
- ORCID
- Venue
- The Journals of Gerontology: Series A
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-08-14
- Volume
- 70
- Issue
- 7
- Pages
- 809-816
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- PMC
- PMC4469006
- OpenAlex
- W2099876949
- Cited by
- 144
- References
- 42
- Citations by year
- 2026: 12 · 2025: 8 · 2024: 22 · 2023: 11 · 2022: 11 · 2021: 14 · 2020: 18 · 2019: 15 · 2018: 11 · 2017: 9 · 2016: 5 · 2015: 8
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- The Journals of Gerontology Series A (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, cc-by-nc)
- reroDoc Digital Library (submittedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc)
- Apollo
- European Conference on Computational Biology
- Funders
- National Institute for Health and Care Research (NF-SI-0512-10053, NF-SI-0514-10027)
- Medical Research Council (MR/M004422/1, MR/L011859/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Aging and Gerontology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- aging, chronological age, plasma proteome, circulating biomarkers, pleiotrophin, birth weight, cardiovascular risk, osteoporosis, gene expression
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Carrier Proteins, Eye Proteins, Female, United Kingdom, Humans, Male, Middle Aged, Nerve Tissue Proteins, Phenotype, Registries, Twins, Cohort Studies, Biomarkers, Cytokines, Insulin-Like Growth Factor Binding Protein 6, Proteomics, Matrix Metalloproteinase 12
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