title: Circulating Proteomic Signatures of Chronological Age.
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.
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London.
authors.forename: Cristina
authors.initials: C
authors.lastname: Menni
authors.affiliation: Institute of Psychiatry, King's College London. Medical Research Council Social, Genetic and Developmental Psychiatry Centre, King's College London.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Kiddle
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mangino
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London.
authors.forename: Ana
authors.initials: A
authors.lastname: Viñuela
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London.
authors.forename: Maria
authors.initials: M
authors.lastname: Psatha
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London.
authors.forename: Claire
authors.initials: C
authors.lastname: Steves
authors.affiliation: 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.
authors.forename: Martina
authors.initials: M
authors.lastname: Sattlecker
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School, Switzerland.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Buil
authors.affiliation: 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.
authors.forename: Stephen
authors.initials: S
authors.lastname: Newhouse
authors.affiliation: SomaLogic, Boulder, Colorado.
authors.forename: Sally
authors.initials: S
authors.lastname: Nelson
authors.affiliation: SomaLogic, Boulder, Colorado.
authors.forename: Stephen
authors.initials: S
authors.lastname: Williams
authors.affiliation: Institute of Psychiatry, King's College London. Medical Research Council Social, Genetic and Developmental Psychiatry Centre, King's College London.
authors.forename: Nicola
authors.initials: N
authors.lastname: Voyle
authors.affiliation: Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Finland.
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.affiliation: Medical University of Lodz, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Kloszewska
authors.affiliation: Institute of Gerontology and Geriatrics, University of Perugia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mecocci
authors.affiliation: Department of Neurology III, Aristotle University, Thessaloniki, Greece.
authors.forename: Magda
authors.initials: M
authors.lastname: Tsolaki
authors.affiliation: Institut national de la sante et de la recherche medicale University of Toulouse, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vellas
authors.affiliation: Department of Psychiatry, University of Oxford.
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London.
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: 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.
authors.forename: Richard
authors.initials: R
authors.lastname: Dobson
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London. Academic Rheumatology, University of Nottingham.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Valdes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000097:blood; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D005136:Eye Proteins / Q000097:blood; D005260:Female; D006801:Humans; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000097:blood; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000097:blood; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000097:blood; D010641:Phenotype; D040901:Proteomics; D012042:Registries; D014427:Twins; D006113:United Kingdom
chemical_list: D015415:Biomarkers; C486602:CHRDL1 protein, human; D002352:Carrier Proteins; D016207:Cytokines; D005136:Eye Proteins; D018976:Insulin-Like Growth Factor Binding Protein 6; D009419:Nerve Tissue Proteins; C066845:pleiotrophin; D053508:Matrix Metalloproteinase 12
keywords: Aging; Aptamers.; Blood biomarkers; Early development; Nucleotide; Proteomics