| Autor: |
Zhang WB; Department of Medicine, Division of Endocrinology, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Aleksic S; Department of Medicine, Division of Endocrinology, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Gao T; Department of Medicine, Division of Endocrinology, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Weiss EF; Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Demetriou E; Ferkauf Graduate School of Psychology, Yeshiva University, New York, NY 10033, USA., Verghese J; Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.; Department of Medicine, Division of Geriatrics, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Holtzer R; Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.; Ferkauf Graduate School of Psychology, Yeshiva University, New York, NY 10033, USA., Barzilai N; Department of Medicine, Division of Endocrinology, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA.; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Milman S; Department of Medicine, Division of Endocrinology, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA.; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA. |
| Abstrakt: |
While the growth hormone/insulin-like growth factor-1 (GH/IGF-1) pathway plays essential roles in growth and development, diminished signaling via this pathway in model organisms extends lifespan and health-span. In humans, circulating IGF-1 and IGF-binding proteins 3 and 1 (IGFBP-3 and 1), surrogate measures of GH/IGF-1 system activity, have not been consistently associated with morbidity and mortality. In a prospective cohort of independently-living older adults ( n = 840, mean age 76.1 ± 6.8 years, 54.5% female, median follow-up 6.9 years), we evaluated the age- and sex-adjusted hazards for all-cause mortality and incident age-related diseases, including cardiovascular disease, diabetes, cancer, and multiple-domain cognitive impairment (MDCI), as predicted by baseline total serum IGF-1, IGF-1/IGFBP-3 molar ratio, IGFBP-3, and IGFBP-1 levels. All-cause mortality was positively associated with IGF-1/IGFBP-3 molar ratio (HR 1.28, 95% CI 1.05-1.57) and negatively with IGFBP-3 (HR 0.82, 95% CI 0.680-0.998). High serum IGF-1 predicted greater risk for MDCI (HR 1.56, 95% CI 1.08-2.26) and composite incident morbidity (HR 1.242, 95% CI 1.004-1.538), whereas high IGFBP-1 predicted lower risk for diabetes (HR 0.50, 95% CI 0.29-0.88). In conclusion, higher IGF-1 levels and bioavailability predicted mortality and morbidity risk, supporting the hypothesis that diminished GH/IGF-1 signaling may contribute to human longevity and health-span. |
