title: Adipose endocrine function, insulin-like growth factor-1 axis, and exceptional survival beyond 100 years of age.
abstract: BACKGROUND
  Observational studies have demonstrated similarities between the underpinning of frailty and biological features of centenarians, suggesting that adaptability to age-related multiple physiological decline may be a core component of successful aging. The aim of this study is to determine whether hormonal pathways potentially involved in energy homeostasis contribute to survival beyond 100 years of age.
  
  
  METHODS
  We assessed a total of 252 centenarians (mean [standard deviation (SD)] age, 101.5 (1.8) years, range 100-108 years) using a complete set of biomarkers of adipose endocrine function and the insulin-like growth factor-1 (IGF-1) axis. Conventional risk factors at baseline were also assessed. The participants were followed up for all-cause mortality every 12 months by telephone contact.
  
  
  RESULTS
  During 2253 days of follow-up, 208 centenarians (82.5%) died. The lowest tertile of leptin and the highest tertile of tumor necrosis factor-alpha were associated with higher mortality risk among centenarians after adjusting for age (per 6-month increase), sex, education, smoking, activities of daily living (ADL), cognitive function, and comorbidities (hazard ratio [HR] 1.6; 95% confidence interval [CI], 1.14-2.35; and HR 1.45; 95% CI, 1.00-2.08, respectively). The lowest tertiles of both IGF-1 and IGF binding protein 3 (IGFBP3) were also associated with increased mortality. The adipose risk score, indicating cumulative effects of adipokine dysregulation, was strongly associated with increased mortality risk; ADL; cognitive function; and levels of albumin, cholinesterase, high-density lipoprotein-cholesterol, C-reactive protein, interleukin 6, and IGF-1 at baseline.
  
  
  CONCLUSIONS
  The results suggested that preservation of adipose endocrine function and the IGF-1 axis may be potentially important for maintaining health and function and promoting survival at an extremely old age.
authors.affiliation: Division of Geriatric Medicine, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. yasumich@sc.itc.keio.ac.jp
authors.forename: Yasumichi
authors.initials: Y
authors.lastname: Arai
authors.forename: Michiyo
authors.initials: M
authors.lastname: Takayama
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Gondo
authors.forename: Hiroki
authors.initials: H
authors.lastname: Inagaki
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamura
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakazawa
authors.forename: Toshio
authors.initials: T
authors.lastname: Kojima
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ebihara
authors.forename: Kenichirou
authors.initials: K
authors.lastname: Shimizu
authors.forename: Yukie
authors.initials: Y
authors.lastname: Masui
authors.forename: Koji
authors.initials: K
authors.lastname: Kitagawa
authors.forename: Toru
authors.initials: T
authors.lastname: Takebayashi
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hirose
mesh_terms: D000273:Adipose Tissue / Q000502:physiology*; D000369:Aged, 80 and over / Q000502:physiology*; D015897:Comorbidity; D004702:Endocrine Glands / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D008136:Longevity / Q000502:physiology*; D008297:Male; D014041:Tokyo
chemical_list: D007334:Insulin-Like Growth Factor I