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.