Insulin-like Growth Factor-1 and IGF Binding Proteins Predict All-Cause Mortality and Morbidity in Older Adults.

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Author(s): Zhang WB;Zhang WB; Aleksic S; Aleksic S; Gao T; Gao T; Weiss EF; Weiss EF; Demetriou E; Demetriou E; Verghese J; Verghese J; Verghese J; Holtzer R; Holtzer R; Holtzer R; Barzilai N; Barzilai N; Barzilai N; Milman S; Milman S; Milman S
Source:
Cells [Cells] 2020 Jun 01; Vol. 9 (6). Date of Electronic Publication: 2020 Jun 01.
Publication Type:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Language:
English

Additional Information
- Source:
  Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE
- Publication Information:
  Original Publication: Basel, Switzerland : MDPI
- Subject Terms:
  Morbidity* ; Mortality*; Insulin-Like Growth Factor Binding Protein 1/*blood ; Insulin-Like Growth Factor Binding Protein 3/*blood ; Insulin-Like Growth Factor I/*metabolism; Aged ; Cohort Studies ; Female ; Humans ; Male ; Risk Factors
- Abstract:
  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.
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- Grant Information:
  R01 AG057909 United States AG NIA NIH HHS; R01 AG044829 United States AG NIA NIH HHS; R01 AG061155 United States AG NIA NIH HHS; P30 DK020541 United States DK NIDDK NIH HHS; UG3 NS105565 United States NS NINDS NIH HHS; R01 AG050448 United States AG NIA NIH HHS; R01 NS109023 United States NS NINDS NIH HHS; T32 AG023475 United States AG NIA NIH HHS; P30 AG038072 United States AG NIA NIH HHS; K23 AG051148 United States AG NIA NIH HHS; UL1 TR002556 United States TR NCATS NIH HHS
- Contributed Indexing:
  Keywords: IGF-1; IGFBP-1; IGFBP-3; age-related disease; cognitive impairment; diabetes; health-span; longevity; older adults
- Accession Number:
  0 (IGFBP1 protein, human)
  0 (IGFBP3 protein, human)
  0 (Insulin-Like Growth Factor Binding Protein 1)
  0 (Insulin-Like Growth Factor Binding Protein 3)
  67763-96-6 (Insulin-Like Growth Factor I)
- Publication Date:
  Date Created: 20200605 Date Completed: 20210305 Latest Revision: 20220826
- Publication Date:
  20240104
- Accession Number:
  PMC7349399
- Accession Number:
  10.3390/cells9061368
- Accession Number:
  32492897

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