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Adipose Endocrine Function, Insulin-Like Growth Factor-1 Axis, and Exceptional Survival Beyond 100 Years of Age

¹ Division of Geriatric Medicine, Department of Internal Medicine, and ² Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan.
³ Tokyo Metropolitan Institute of Gerontology, Japan.
⁴ Mizuho Health Insurance Society, Tokyo, Japan.
⁵ Health Care Center, Shoko Chukin Bank, Tokyo, Japan.
⁶ Human Genome Research Group, Genomic Sciences Center, RIKEN, Yokohama, Japan.
⁷ Tohoku Bunka Gakuen University, Miyagi, Japan.

Address correspondence to Yasumichi Arai, MD, PhD, Division of Geriatric Medicine, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. E-mail: yasumich{at}sc.itc.keio.ac.jp

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- 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.

Key Words: Centenarians • Leptin • Adiponectin • Tumor necrosis factor-alpha • Insulin-like growth factor 1 • Mortality • Frailty • Metabolic network

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