title: Metabolic profiles of biological aging in American Indians: the Strong Heart Family Study.
abstract: Short telomere length, a marker of biological aging, has been associated with age-related metabolic disorders. Telomere attrition induces profound metabolic dysfunction in animal models, but no study has examined the metabolome of telomeric aging in human. Here we studied 423 apparently healthy American Indians participating in the Strong Family Heart Study. Leukocyte telomere length (LTL) was measured by qPCR. Metabolites in fasting plasma were detected by untargeted LC/MS. Associations of LTL with each metabolite and their combined effects were examined using generalized estimating equation adjusting for chronological age and other aging-related factors. Multiple testing was corrected using the q-value method (q<0.05). Of the 1,364 distinct m/z features detected, nineteen metabolites in the classes of glycerophosphoethanolamines, glycerophosphocholines, glycerolipids, bile acids, isoprenoids, fatty amides, or L-carnitine ester were significantly associated with LTL, independent of chronological age and other aging-related factors. Participants with longer (top tertile) and shorter (bottom tertile) LTL were clearly separated into distinct groups using a multi-marker score comprising of all these metabolites, suggesting that these newly detected metabolites could be novel metabolic markers of biological aging. This is the first study to interrogate the human metabolome of telomeric aging. Our results provide initial evidence for a metabolic control of LTL and may reveal previously undescribed new roles of various lipids in the aging process.
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health, New Orleans, LA 70112; USA.
authors.forename: Jinying
authors.initials: J
authors.lastname: Zhao
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.forename: Karan
authors.initials: K
authors.lastname: Uppal
authors.forename: ViLinh T
authors.initials: VT
authors.lastname: Tran
authors.forename: Tianwei
authors.initials: T
authors.lastname: Yu
authors.forename: Jue
authors.initials: J
authors.lastname: Lin
authors.forename: Tet
authors.initials: T
authors.lastname: Matsuguchi
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Blackburn
authors.forename: Dean
authors.initials: D
authors.lastname: Jones
authors.forename: Elisa T
authors.initials: ET
authors.lastname: Lee
authors.affiliation: Medstar Research Institute and Georgetown and Howard Universities Centers for Translational Sciences, Washington, DC 20007.
authors.forename: Barbara V
authors.initials: BV
authors.lastname: Howard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006331:Heart Diseases / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D055442:Metabolome / Q000235:genetics*; D008875:Middle Aged; D016615:Telomere / Q000235:genetics; D059505:Telomere Homeostasis / Q000235:genetics; D055815:Young Adult
chemical_list: D015415:Biomarkers