Metabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty
Global ageing poses a substantial economic burden on health and social care costs. Enabling a greater proportion of older people to stay healthy for longer is key to the future sustainability of health, social and economic policy. Frailty and associated decrease in resilience plays a central role in poor health in later life. In this study, we present a population level assessment of the metabolic phenotype associated with frailty. Analysis of serum from 1191 older individuals (aged between 56 and 84 years old) and subsequent longitudinal validation (on 786 subjects) was carried out using liquid and gas chromatography-mass spectrometry metabolomics and stratified across a frailty index designed to quantitatively summarize vulnerability. Through multivariate regression and network modelling and mROC modeling we identified 12 significant metabolites (including three tocotrienols and six carnitines) that differentiate frail and non-frail phenotypes. Our study provides evidence that the dysregulation of carnitine shuttle and vitamin E pathways play a role in the risk of frailty.
2019
2019-11-08 03:31:22
1033
metabolomics, frailty, ageing, LC-MS, serum
r6
Nicholas
Rattray
70
Drupad
Trivedi
70
Yun
Xu
70
Tarani
Chandola
70
Caroline
Johnson
70
Alan
Marshall
70
Krisztina
Mekli
70
Zahra
Rattray
70
Gindo
Tampubolon
70
Bram
Vanhoutte
70
Iain R.
White
70
Frederick
Wu
70
Neil
Pendleton
70
James
Nazroo
70
Royston
Goodacre
70
COBISS_ID
3
5478907
DOI
15
doi:10.1038/s41467-019-12716-2
NUK URN
18
URN:SI:UNG:REP:FJYX4KQN
s41467-019-12716-2.pdf
2461246
Predstavitvena datoteka
2019-11-08 03:32:53
0
Izvorni URL
2019-11-08 03:34:22