title: Circulating levels of fibroblast growth factor-21 increase with age independently of body composition indices among healthy individuals.
abstract: BACKGROUND
  Circulating FGF21 levels are commonly elevated in disease states. There is limited information regarding concentrations of circulating FGF21 in the absence of disease, as well as age-related differences in body composition that may contribute to FGF21 regulation across groups.
  
  
  OBJECTIVE
  The objectives of this study were to assess FGF21 levels across age groups (childhood to elder adulthood), and investigate whether body composition indices are associated with age-related differences in circulating FGF21.
  
  
  METHODS
  We cross-sectionally analyzed serum concentrations of FGF21 in 184 healthy subjects aged 5-80y (45% male). Multiple linear regression was performed to assess the independent association of categorical age (children: 5-12y, young adults: 20-29y, adults: 30-50y, older adults: 55-64y, elder adults: 65-80y) with FGF21 concentration taking into account DXA-measured body composition indices [bone mineral density (BMD) and percent lean, trunk, and fat mass]. We also stratified analysis by tertile of FGF21.
  
  
  RESULTS
  Incremental increases in FGF21 levels were observed across age groups (youngest to highest). Age group was positively associated with FGF21 level independent of body composition indices (age group variable: β=0.25, 0.24, 0.24, 0.23, allP<0.0001, controlling for percent lean, BMD, percent fat, and percent trunk fat, respectively). By FGF21 tertile, age group was associated with FGF21 in the lowest tertile only (β=13.1, 0.19, 0.18, all P≤0.01, accounting for percent lean, fat and trunk fat, respectively), but not when accounting for BMD.
  
  
  CONCLUSIONS
  Our findings in a healthy population display an age-related increase in serum FGF21, highlighting a potential age effect in response to metabolic demand over the lifecourse. FGF21 levels increase with age independently of body composition. At lower levels of FGF21, BMD, but not other body composition parameters, attenuates the association between FGF21 level and age, suggesting the metabolic demand of the skeleton may provide a link between FGF21 and energy metabolism.
authors.affiliation: Department of Pediatrics, Division of Pediatric Endocrinology, Children's Hospital of Alabama (COA), University of Alabama at Birmingham (UAB), CPPII M30, 1601 4 Ave S, Birmingham, AL 35233; hankslj@uab.edu.
authors.forename: Lynae J
authors.initials: LJ
authors.lastname: Hanks
authors.affiliation: Department of Medicine, UAB, ZRB 614, 1720 2nd AVE S, Birmingham, AL 35294-0006; ogutierr@uab.edu.
authors.forename: Orlando M
authors.initials: OM
authors.lastname: Gutiérrez
authors.affiliation: Department of Cell, Developmental, and Integrative Biology, Center for Exercise Medicine, Geriatric Research, Education, and Clinical Center, Birmingham Veterans' Affairs (VA) Medical Center, UAB, MCLM 966, 1530 3 Ave S, Birmingham, AL 35294-0005; mbamman@uab.edu.
authors.forename: Marcas M
authors.initials: MM
authors.lastname: Bamman
authors.affiliation: Department of Pediatrics, Division of Pediatric Endocrinology, COA, UAB, CPPII M30, 1601 4 Ave S, Birmingham, AL 35233; aashraf@peds.uab.edu.
authors.forename: Ambika
authors.initials: A
authors.lastname: Ashraf
authors.affiliation: Department of Pediatrics, Division of Pediatric Endocrinology, COA, UAB, CPPII M30, 1601 4 Ave S, Birmingham, AL 35233; KMcCormick@peds.uab.edu.
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: McCormick
authors.affiliation: Department of Pediatrics, Division of General Pediatrics and Adolescent Medicine, COA, UAB, CPPI 310, 1601 4 Ave S, Birmingham, AL 35233-1711; kcasazza@peds.uab.edu.
authors.forename: Krista
authors.initials: K
authors.lastname: Casazza
keywords: Fibroblast growth factor 21; aging; body composition