title: A metabolic view on menopause and ageing.
abstract: The ageing of the global population calls for a better understanding of age-related metabolic consequences. Here we report the effects of age, sex and menopause on serum metabolites in 26,065 individuals of Northern European ancestry. Age-specific metabolic fingerprints differ significantly by gender and, in females, a substantial atherogenic shift overlapping the time of menopausal transition is observed. In meta-analysis of 10,083 women, menopause status associates with amino acids glutamine, tyrosine and isoleucine, along with serum cholesterol measures and atherogenic lipoproteins. Among 3,204 women aged 40-55 years, menopause status associates additionally with glycine and total, monounsaturated, and omega-7 and -9 fatty acids. Our findings suggest that, in addition to lipid alterations, menopause may contribute to future metabolic and cardiovascular risk via influencing amino-acid concentrations, adding to the growing evidence of the importance of amino acids in metabolic disease progression. These observations shed light on the metabolic consequences of ageing, gender and menopause at the population level.
authors.affiliation: 1] Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Biomedicum 1, Haartmaninkatu 8, Helsinki 00290, Finland [2] Institute for Molecular Medicine (FIMM), University of Helsinki, Biomedicum 2, Tukholmankatu 8, Helsinki 00290, Finland [3] Department of Obstetrics and Gynecology, Helsinki University Central Hospital and University of Helsinki, Haartmaninkatu 2, Helsinki 00290, Finland [4].
authors.forename: Kirsi
authors.initials: K
authors.lastname: Auro
authors.affiliation: 1] Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Biomedicum 1, Haartmaninkatu 8, Helsinki 00290, Finland [2] Institute for Molecular Medicine (FIMM), University of Helsinki, Biomedicum 2, Tukholmankatu 8, Helsinki 00290, Finland [3].
authors.forename: Anni
authors.initials: A
authors.lastname: Joensuu
authors.affiliation: Estonian Genome Center, University of Tartu, Riia 23b, Tartu 51010, Estonia.
authors.forename: Krista
authors.initials: K
authors.lastname: Fischer
authors.affiliation: 1] Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Biomedicum 1, Haartmaninkatu 8, Helsinki 00290, Finland [2] Institute for Molecular Medicine (FIMM), University of Helsinki, Biomedicum 2, Tukholmankatu 8, Helsinki 00290, Finland [3] Computational Medicine, Institute of Health Sciences, University of Oulu, Pentti Kaiteran katu 1, Oulu 90570, Finland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kettunen
authors.affiliation: 1] Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Biomedicum 1, Haartmaninkatu 8, Helsinki 00290, Finland [2] Institute for Molecular Medicine (FIMM), University of Helsinki, Biomedicum 2, Tukholmankatu 8, Helsinki 00290, Finland.
authors.forename: Perttu
authors.initials: P
authors.lastname: Salo
authors.affiliation: 1] Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Biomedicum 1, Haartmaninkatu 8, Helsinki 00290, Finland [2] Institute for Molecular Medicine (FIMM), University of Helsinki, Biomedicum 2, Tukholmankatu 8, Helsinki 00290, Finland.
authors.forename: Hannele
authors.initials: H
authors.lastname: Mattsson
authors.affiliation: Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Biomedicum 1, Haartmaninkatu 8, Helsinki 00290, Finland.
authors.forename: Marjo
authors.initials: M
authors.lastname: Niironen
authors.affiliation: 1] Institute for Molecular Medicine (FIMM), University of Helsinki, Biomedicum 2, Tukholmankatu 8, Helsinki 00290, Finland [2] Departmentof Public Health, Hjelt Institute, University of Helsinki, PO Box 41 Mannerheimintie 172, Helsinki 00014, Finland [3] Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, PO Box 30 (Mannerheimintie 166), Helsinki 00300, Finland.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.affiliation: 1] Chronic Disease Epidemiology and Prevention Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Mannerheimintie 166, Helsinki 00300, Finland [2] Department of General Practice and Primary Health Care, University of Helsinki, PL 20, Tukholmankatu 8B, Helsinki 00029, Finland [3] Vasa Central Hospital, Sandviksgatan 2-4, Vasa 65130, Finland [4] Folkhälsan Research Centre, Helsingfors Universitet, PB 63, Helsinki 00014, Finland [5] Unit of General Practice, Helsinki University Central Hospital, Haartmaninkatu 4, Helsinki 00290, Finland.
authors.forename: Johan G
authors.initials: JG
authors.lastname: Eriksson
authors.affiliation: Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere School of Medicine, Tampere University, Kalevantie 4, Tampere 33014, Finland.
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.affiliation: Department of Clinical Physiology and Nuclear Medicine, Research Centre of Applied and Preventive Cardiovascular Medicine, Turku University Hospital, University of Turku, Kiinamyllynkatu 4-8, Turku 20521, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Raitakari
authors.affiliation: Chronic Disease Epidemiology and Prevention Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Mannerheimintie 166, Helsinki 00300, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Jula
authors.affiliation: Department of Obstetrics and Gynecology, Helsinki University Central Hospital and University of Helsinki, Haartmaninkatu 2, Helsinki 00290, Finland.
authors.forename: Aila
authors.initials: A
authors.lastname: Tiitinen
authors.affiliation: 1] Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Biomedicum 1, Haartmaninkatu 8, Helsinki 00290, Finland [2] Institute for Molecular Medicine (FIMM), University of Helsinki, Biomedicum 2, Tukholmankatu 8, Helsinki 00290, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.affiliation: 1] Computational Medicine, Institute of Health Sciences, University of Oulu, Pentti Kaiteran katu 1, Oulu 90570, Finland [2] NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Yliopistonranta 1 PL 1627, Kuopio 70211, Finland.
authors.forename: Pasi
authors.initials: P
authors.lastname: Soininen
authors.affiliation: 1] Computational Medicine, Institute of Health Sciences, University of Oulu, Pentti Kaiteran katu 1, Oulu 90570, Finland [2] NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Yliopistonranta 1 PL 1627, Kuopio 70211, Finland.
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Kangas
authors.affiliation: Department of Clinical Physiology, Tampere University Hospital and University of Tampere School of Medicine, Tampere University, Kalevantie 4, Tampere 33014, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.affiliation: Chronic Disease Epidemiology and Prevention Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Mannerheimintie 166, Helsinki 00300, Finland.
authors.forename: Aki S
authors.initials: AS
authors.lastname: Havulinna
authors.affiliation: 1] Computational Medicine, Institute of Health Sciences, University of Oulu, Pentti Kaiteran katu 1, Oulu 90570, Finland [2] NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Yliopistonranta 1 PL 1627, Kuopio 70211, Finland [3] Oulu University Hospital, Kajaanintie 50, Oulu 90220, Finland [4] Computational Medicine, School of Social and Community Medicine and Medical Research Council Integrative Epidemiology Unit, University of Bristol, Senate House, Tyndall Avenue, Bristol, City of Bristol BS8 1TH, UK.
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
authors.affiliation: Chronic Disease Epidemiology and Prevention Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Mannerheimintie 166, Helsinki 00300, Finland.
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.affiliation: Estonian Genome Center, University of Tartu, Riia 23b, Tartu 51010, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.affiliation: 1] Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Biomedicum 1, Haartmaninkatu 8, Helsinki 00290, Finland [2] Institute for Molecular Medicine (FIMM), University of Helsinki, Biomedicum 2, Tukholmankatu 8, Helsinki 00290, Finland [3] Estonian Genome Center, University of Tartu, Riia 23b, Tartu 51010, Estonia.
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D000596:Amino Acids / Q000097:blood; D001769:Blood / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000378:metabolism; D015331:Cohort Studies; D004957:Estonia; D005260:Female; D005387:Finland; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008593:Menopause / Q000378:metabolism*; D008875:Middle Aged; D012307:Risk Factors; D044465:White People; D055815:Young Adult
chemical_list: D000596:Amino Acids; D008055:Lipids