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Circulating Proteomic Signatures of Chronological Age.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Menni, Cristina 
Kiddle, Steven J 
Mangino, Massimo 
Viñuela, Ana 
Psatha, Maria 

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.

Description

Keywords

Aging, Aptamers., Blood biomarkers, Early development, Nucleotide, Proteomics, Adult, Aged, Aged, 80 and over, Aging, Biomarkers, Carrier Proteins, Cohort Studies, Cytokines, Eye Proteins, Female, Humans, Insulin-Like Growth Factor Binding Protein 6, Male, Matrix Metalloproteinase 12, Middle Aged, Nerve Tissue Proteins, Phenotype, Proteomics, Registries, Twins, United Kingdom

Journal Title

J Gerontol A Biol Sci Med Sci

Conference Name

Journal ISSN

1079-5006
1758-535X

Volume Title

70

Publisher

Oxford University Press (OUP)
Sponsorship
Medical Research Council (G0801464)
Medical Research Council (G0801464/1)