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Circulating Proteomic Signatures of Chronological Age.

  • Menni C Department of Twin Research and Genetic Epidemiology, King's College London.
  • Kiddle SJ Institute of Psychiatry, King's College London. Medical Research Council Social, Genetic and Developmental Psychiatry Centre, King's College London.
  • Mangino M Department of Twin Research and Genetic Epidemiology, King's College London.
  • Viñuela A Department of Twin Research and Genetic Epidemiology, King's College London.
  • Psatha M Department of Twin Research and Genetic Epidemiology, King's College London.
  • Steves C Department of Twin Research and Genetic Epidemiology, King's College London.
  • Sattlecker M 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.
  • Buil A Department of Genetic Medicine and Development, University of Geneva Medical School, Switzerland.
  • Newhouse S 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.
  • Nelson S SomaLogic, Boulder, Colorado.
  • Williams S SomaLogic, Boulder, Colorado.
  • Voyle N Institute of Psychiatry, King's College London. Medical Research Council Social, Genetic and Developmental Psychiatry Centre, King's College London.
  • Soininen H Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Finland.
  • Kloszewska I Medical University of Lodz, Poland.
  • Mecocci P Institute of Gerontology and Geriatrics, University of Perugia, Italy.
  • Tsolaki M Department of Neurology III, Aristotle University, Thessaloniki, Greece.
  • Vellas B Institut national de la sante et de la recherche medicale University of Toulouse, France.
  • Lovestone S Department of Psychiatry, University of Oxford.
  • Spector TD Department of Twin Research and Genetic Epidemiology, King's College London.
  • Dobson R 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.
  • Valdes AM Department of Twin Research and Genetic Epidemiology, King's College London. Academic Rheumatology, University of Nottingham.
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  • 2014-08-16
Published in:
  • The journals of gerontology. Series A, Biological sciences and medical sciences. - 2015
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
English 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.
Language
  • English
Open access status
hybrid
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https://sonar.ch/global/documents/109338
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