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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.

Background: Research in Western countries has shown most centenarians to be survivors with multiple comorbidities. However, Japanese centenarians' morbidity and its relationship to functional status has yet to be elucidated. The aim of this study is to clarify the association of morbidity with the physical and cognitive function of centenarians. We examined Tokyo-area centenarians to determine their kinds of morbidity profiles and how such morbidity related to their functional status., Methods: We studied 302 centenarians living in Tokyo (101.2+/-1.8 years; 65 men, 237 women), and assessed their physical status, morbidity, and use of medication. Activities of daily living and cognitive function were also assessed using the Barthel Index and the Clinical Dementia Rating., Results: More than 95% of the centenarians had chronic diseases. Both the physical and cognitive functions were significantly higher in men. The present and previous illnesses most frequently included hypertension, heart disease, stroke, fractures, and cataracts. Fractures were observed significantly more frequently in women. Diabetes mellitus was uncommon. The physical and cognitive function of centenarians with a history of stroke or fracture were particularly poor, whereas those centenarians with hypertension tended to show a high level of physical and cognitive function., Conclusions: Almost all centenarians had chronic diseases. Stroke and fracture were correlated with poorer function; therefore, we hypothesize that prevention of stroke and fracture might improve functional status in the oldest-old.