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J Gerontol A Biol Sci Med Sci. 2015 Jul;70(7):809-16. doi: 10.1093/gerona/glu121. Epub 2014 Aug 14.

Circulating Proteomic Signatures of Chronological Age.

Author information

1
Department of Twin Research and Genetic Epidemiology, King's College London.
2
Institute of Psychiatry, King's College London. Medical Research Council Social, Genetic and Developmental Psychiatry Centre, King's College London.
3
Institute of Psychiatry, King's College London. National Institute for Health Research Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London.
4
Department of Genetic Medicine and Development, University of Geneva Medical School, Switzerland.
5
SomaLogic, Boulder, Colorado.
6
Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Finland.
7
Medical University of Lodz, Poland.
8
Institute of Gerontology and Geriatrics, University of Perugia, Italy.
9
Department of Neurology III, Aristotle University, Thessaloniki, Greece.
10
Institut national de la sante et de la recherche medicale University of Toulouse, France.
11
Department of Psychiatry, University of Oxford.
12
Department of Twin Research and Genetic Epidemiology, King's College London. Academic Rheumatology, University of Nottingham.

Abstract

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.

KEYWORDS:

Aging; Aptamers.; Blood biomarkers; Early development; Nucleotide; Proteomics

PMID:
25123647
PMCID:
PMC4469006
DOI:
10.1093/gerona/glu121
[Indexed for MEDLINE]
Free PMC Article
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