Measuring biological age using omics data

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(12), P. 715 - 727

Published: June 17, 2022

Language: Английский

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Metabolic Signatures of Insulin Resistance in 7,098 Young Adults

Diabetes, Journal Year: 2012, Volume and Issue: 61(6), P. 1372 - 1380

Published: April 18, 2012

Metabolite associations with insulin resistance were studied in 7,098 young Finns (age 31 ± 3 years; 52% women) to elucidate underlying metabolic pathways. Insulin was assessed by the homeostasis model (HOMA-IR) and circulating metabolites quantified high-throughput nuclear magnetic resonance spectroscopy two population-based cohorts. Associations analyzed using regression models adjusted for age, waist, standard lipids. Branched-chain aromatic amino acids, gluconeogenesis intermediates, ketone bodies, fatty acid composition saturation associated HOMA-IR (P < 0.0005 20 metabolite measures). Leu, Ile, Val, Tyr displayed sex- obesity-dependent interactions, being significant women only if they abdominally obese. Origins of fasting levels dietary physical activity data. Here, protein energy intake Phe, Tyr, Gln but not index. We further tested 12 genetic variants regulating also contributed resistance. The determinants HOMA-IR, exception a variant GCKR metabolites, including acids 0.0005). Nonetheless, signatures extending beyond obesity lipid abnormalities reflected degree evidenced young, normoglycemic adults sex-specific fingerprints.

Language: Английский

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A metabolic profile of all-cause mortality risk identified in an observational study of 44,168 individuals

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Aug. 20, 2019

Abstract Predicting longer-term mortality risk requires collection of clinical data, which is often cumbersome. Therefore, we use a well-standardized metabolomics platform to identify metabolic predictors long-term in the circulation 44,168 individuals (age at baseline 18–109), whom 5512 died during follow-up. We apply stepwise (forward-backward) procedure based on meta-analysis results and 14 circulating biomarkers independently associating with all-cause mortality. Overall, these associations are similar men women across different age strata. subsequently show that prediction accuracy 5- 10-year model containing identified sex ( C -statistic = 0.837 0.830, respectively) better than conventional factors for 0.772 0.790, respectively). The profile as predictor or surrogate endpoint studies needs further investigation.

Language: Английский

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Metabolic Signatures of Adiposity in Young Adults: Mendelian Randomization Analysis and Effects of Weight Change

PLoS Medicine, Journal Year: 2014, Volume and Issue: 11(12), P. e1001765 - e1001765

Published: Dec. 9, 2014

Background Increased adiposity is linked with higher risk for cardiometabolic diseases. We aimed to determine what extent elevated body mass index (BMI) within the normal weight range has causal effects on detailed systemic metabolite profile in early adulthood. Methods and Findings used Mendelian randomization estimate of BMI 82 metabolic measures 12,664 adolescents young adults from four population-based cohorts Finland (mean age 26 y, 16–39 y; 51% women; mean ± standard deviation 24±4 kg/m2). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics biochemical assays. In cross-sectional analyses, was adversely associated markers throughout profile, including lipoprotein subclasses, fatty acid composition, amino acids, inflammatory markers, various hormones (p<0.0005 68 measures). Metabolite associations generally stronger men than women (median 136%, interquartile 125%–183%). A gene score predisposition BMI, composed 32 established genetic correlates, as instrument assess causality. Causal closely matched observational estimates (correspondence 87%±3%; R2 = 0.89), suggesting causative influences levels numerous 24 measures), lipid subclasses particle size, branched-chain aromatic inflammation-related glycoprotein acetyls. analyses certain potential sex differences warrant statistical power. changes change during 6 y follow-up examined 1,488 individuals. Change accompanied widespread changes, which had an association pattern similar that observations, yet greater 160%±2%; 0.92). Conclusions indicates adverse increased multiple across non-obese range. Consistent adiposity, paralleled extensive a broadly modifiable Please see later article Editors' Summary

Language: Английский

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Metabonomic, transcriptomic, and genomic variation of a population cohort

Molecular Systems Biology, Journal Year: 2010, Volume and Issue: 6(1)

Published: Jan. 1, 2010

Language: Английский

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Hyperglycemia and a Common Variant ofGCKRAre Associated With the Levels of Eight Amino Acids in 9,369 Finnish Men

Diabetes, Journal Year: 2012, Volume and Issue: 61(7), P. 1895 - 1902

Published: May 3, 2012

We investigated the association of glycemia and 43 genetic risk variants for hyperglycemia/type 2 diabetes with amino acid levels in population-based Metabolic Syndrome Men (METSIM) Study, including 9,369 nondiabetic or newly diagnosed type diabetic Finnish men. Plasma eight acids were measured proton nuclear magnetic resonance spectroscopy. Increasing fasting 2-h plasma glucose associated increasing several decreasing histidine glutamine. Alanine, leucine, isoleucine, tyrosine, glutamine predicted incident a 4.7-year follow-up METSIM their effects largely mediated by insulin resistance (except glutamine). also found significant correlations between sensitivity (Matsuda index) mRNA expression genes regulating degradation 200 subcutaneous adipose tissue samples. Only 1 single nucleotide polymorphisms hyperglycemia, glucose-increasing major C allele rs780094 GCKR, was significantly decreased alanine isoleucine elevated In conclusion, branched-chain, aromatic increased glycemia, reflecting, at least part, resistance. one polymorphism hyperglycemia levels.

Language: Английский

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A metabolic view on menopause and ageing

Nature Communications, Journal Year: 2014, Volume and Issue: 5(1)

Published: Aug. 21, 2014

Language: Английский

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Long-term Leisure-time Physical Activity and Serum Metabolome

Circulation, Journal Year: 2012, Volume and Issue: 127(3), P. 340 - 348

Published: Dec. 22, 2012

Long-term physical inactivity seems to cause many health problems. We studied whether persistent activity compared with has a global effect on serum metabolome toward reduced cardiometabolic disease risk.Sixteen same-sex twin pairs (mean age, 60 years) were selected from cohort of the basis their >30-year discordance for activity. Persistently (≥5 active and inactive groups in 3 population-based cohorts ages, 31-52 also (1037 age- sex-matched pairs). Serum was quantified by nuclear magnetic resonance spectroscopy. used permutation analysis estimate significance multivariate combined across all metabolic measures; univariate effects estimated paired testing twins matched cohorts, meta-analysis over substudies. Persistent associated profile (P=0.003), similar pattern observed population differing mean ages. Isoleucine, α1-acid glycoprotein, glucose lower physically than individuals (P<0.001 meta-analysis); fatty acid composition shifted less saturated profile; lipoprotein subclasses very-low-density (P<0.001) higher large very high-density particle concentrations. The findings persisted after adjustment body mass index.The numerous differences found between persistently circulating together indicate better individuals.

Language: Английский

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Association of branched‐chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer's disease: A prospective study in eight cohorts

Alzheimer s & Dementia, Journal Year: 2018, Volume and Issue: 14(6), P. 723 - 733

Published: March 5, 2018

Abstract Introduction Metabolite, lipid, and lipoprotein lipid profiling can provide novel insights into mechanisms underlying incident dementia Alzheimer's disease. Methods We studied eight prospective cohorts with 22,623 participants profiled by nuclear magnetic resonance or mass spectrometry metabolomics. Four were used for discovery replication undertaken in the other four to avoid false positives. For metabolites that survived replication, combined association results are presented. Results Over 246,698 person‐years, 995 745 cases of disease detected, respectively. Three branched‐chain amino acids (isoleucine, leucine, valine), creatinine two very low density (VLDL)‐specific subclasses associated lower risk. One high (HDL; concentration cholesterol esters relative total lipids large HDL) one VLDL (total ratio VLDL) subclass was increased Branched‐chain also decreased risk HDL Discussion Further studies clarify whether these molecules play a causal role pathogenesis merely markers early pathology.

Language: Английский

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Relationship between gut microbiota and circulating metabolites in population-based cohorts

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Dec. 20, 2019

Abstract Gut microbiota has been implicated in major diseases affecting the human population and also linked to triglycerides high-density lipoprotein levels circulation. Recent development metabolomics allows classifying particles into more details. Here, we examine impact of gut on circulating metabolites measured by Nuclear Magnetic Resonance technology 2309 individuals from Rotterdam Study LifeLines-DEEP cohort. We assess relationship between linear regression analysis while adjusting for age, sex, body-mass index, technical covariates, medication use, multiple testing. report an association 32 microbial families genera with very-low-density subfractions, serum lipid measures, glycolysis-related metabolites, ketone bodies, amino acids, acute-phase reaction markers. These observations provide insights role host metabolism support potential as a target therapeutic preventive interventions.

Language: Английский

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