Circulating proteomic signatures of chronological age

TY - JOUR

T1 - Circulating proteomic signatures of chronological age

AU - Menni, Cristina

AU - Kiddle, Steven J.

AU - Mangino, Massimo

AU - Viñuela, Ana

AU - Psatha, Maria

AU - Steves, Claire

AU - Sattlecker, Martina

AU - Buil, Alfonso

AU - Newhouse, Stephen

AU - Nelson, Sally

AU - Williams, Stephen

AU - Voyle, Nicola

AU - Soininen, Hilkka

AU - Kloszewska, Iwona

AU - Mecocci, Patrizia

AU - Tsolaki, Magda

AU - Vellas, Bruno

AU - Lovestone, Simon

AU - Spector, Tim D.

AU - Dobson, Richard

AU - Valdes, Ana M.

PY - 2014/8/14

Y1 - 2014/8/14

N2 - 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.

AB - 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.

KW - Aging

KW - Proteomics

KW - Early development

KW - blood biomarkers

KW - Nucleotide

KW - Aptamers

UR - http://europepmc.org/abstract/med/25123647

U2 - 10.1093/gerona/glu121

DO - 10.1093/gerona/glu121

M3 - Article

C2 - 25123647

SN - 1079-5006

VL - 70

SP - 809

EP - 816

JO - The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

JF - The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

IS - 7

ER -