Trajectories of IGF-I Predict Mortality in Older Adults

The Cardiovascular Health Study

Jason L. Sanders, Wensheng Guo, Ellen S. O'Meara, Robert C. Kaplan, Michael N. Pollak, Traci M. Bartz, Anne B. Newman, Linda P. Fried, Anne R. Cappola

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background Disruption of insulin-like growth factor-I (IGF-I) increases health and life span in animal models, though this is unconfirmed in humans. If IGF-I stability indicates homeostasis, the absolute level of IGF-I may be less clinically relevant than maintaining an IGF-I setpoint. Methods Participants were 945 U.S. community-dwelling individuals aged ≥65 years enrolled in the Cardiovascular Health Study with IGF-I levels at 3-6 timepoints. We examined the association of baseline IGF-I level, trajectory slope, and variability around the trajectory with mortality. Results There were 633 deaths over median 11.3 years of follow-up. Lower IGF-I levels, declining or increasing slope, and increasing variability were each individually associated with higher mortality (all p <.001). In an adjusted model including all three trajectory parameters, baseline IGF-I levels <70 ng/mL (hazard ratio [HR] 1.58, 95% CI 1.28-1.96 relative to IGF-I levels of 170 ng/mL), steep declines and steep increases in trajectory slope (HR 2.22, 1.30-3.80 for a 15% decline; HR 1.40, 1.07-1.84 for a 10% decline; HR 1.80, 1.12-2.89 for a 15% increase; HR 1.31, 1.00-1.72 for a 10% increase, each vs no change), and variability ≥10% (HR 1.59, 1.09-2.32 for ≥ 30%; HR 1.36, 1.06-1.75 for 20%; and HR 1.17, 1.03-1.32 for 10% variability, each vs 0%) in IGF-I levels were independently associated with mortality. Conclusions In contrast to data from animal models, low IGF-I levels are associated with higher mortality in older humans. Irrespective of the actual IGF-I level, older individuals with stability of IGF-I levels have lower mortality than those whose IGF-I levels fluctuate over time.

Original languageEnglish (US)
Pages (from-to)953-959
Number of pages7
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume73
Issue number7
DOIs
StatePublished - Jun 14 2018

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Insulin-Like Growth Factor I
Mortality
Health
Animal Models
Independent Living
Homeostasis

Keywords

  • Aging
  • Insulin like growth factor
  • Longevity
  • Longitudinal
  • Trajectory

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

Trajectories of IGF-I Predict Mortality in Older Adults : The Cardiovascular Health Study. / Sanders, Jason L.; Guo, Wensheng; O'Meara, Ellen S.; Kaplan, Robert C.; Pollak, Michael N.; Bartz, Traci M.; Newman, Anne B.; Fried, Linda P.; Cappola, Anne R.

In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, Vol. 73, No. 7, 14.06.2018, p. 953-959.

Research output: Contribution to journalArticle

Sanders, Jason L. ; Guo, Wensheng ; O'Meara, Ellen S. ; Kaplan, Robert C. ; Pollak, Michael N. ; Bartz, Traci M. ; Newman, Anne B. ; Fried, Linda P. ; Cappola, Anne R. / Trajectories of IGF-I Predict Mortality in Older Adults : The Cardiovascular Health Study. In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences. 2018 ; Vol. 73, No. 7. pp. 953-959.
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abstract = "Background Disruption of insulin-like growth factor-I (IGF-I) increases health and life span in animal models, though this is unconfirmed in humans. If IGF-I stability indicates homeostasis, the absolute level of IGF-I may be less clinically relevant than maintaining an IGF-I setpoint. Methods Participants were 945 U.S. community-dwelling individuals aged ≥65 years enrolled in the Cardiovascular Health Study with IGF-I levels at 3-6 timepoints. We examined the association of baseline IGF-I level, trajectory slope, and variability around the trajectory with mortality. Results There were 633 deaths over median 11.3 years of follow-up. Lower IGF-I levels, declining or increasing slope, and increasing variability were each individually associated with higher mortality (all p <.001). In an adjusted model including all three trajectory parameters, baseline IGF-I levels <70 ng/mL (hazard ratio [HR] 1.58, 95{\%} CI 1.28-1.96 relative to IGF-I levels of 170 ng/mL), steep declines and steep increases in trajectory slope (HR 2.22, 1.30-3.80 for a 15{\%} decline; HR 1.40, 1.07-1.84 for a 10{\%} decline; HR 1.80, 1.12-2.89 for a 15{\%} increase; HR 1.31, 1.00-1.72 for a 10{\%} increase, each vs no change), and variability ≥10{\%} (HR 1.59, 1.09-2.32 for ≥ 30{\%}; HR 1.36, 1.06-1.75 for 20{\%}; and HR 1.17, 1.03-1.32 for 10{\%} variability, each vs 0{\%}) in IGF-I levels were independently associated with mortality. Conclusions In contrast to data from animal models, low IGF-I levels are associated with higher mortality in older humans. Irrespective of the actual IGF-I level, older individuals with stability of IGF-I levels have lower mortality than those whose IGF-I levels fluctuate over time.",
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AU - Sanders, Jason L.

AU - Guo, Wensheng

AU - O'Meara, Ellen S.

AU - Kaplan, Robert C.

AU - Pollak, Michael N.

AU - Bartz, Traci M.

AU - Newman, Anne B.

AU - Fried, Linda P.

AU - Cappola, Anne R.

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N2 - Background Disruption of insulin-like growth factor-I (IGF-I) increases health and life span in animal models, though this is unconfirmed in humans. If IGF-I stability indicates homeostasis, the absolute level of IGF-I may be less clinically relevant than maintaining an IGF-I setpoint. Methods Participants were 945 U.S. community-dwelling individuals aged ≥65 years enrolled in the Cardiovascular Health Study with IGF-I levels at 3-6 timepoints. We examined the association of baseline IGF-I level, trajectory slope, and variability around the trajectory with mortality. Results There were 633 deaths over median 11.3 years of follow-up. Lower IGF-I levels, declining or increasing slope, and increasing variability were each individually associated with higher mortality (all p <.001). In an adjusted model including all three trajectory parameters, baseline IGF-I levels <70 ng/mL (hazard ratio [HR] 1.58, 95% CI 1.28-1.96 relative to IGF-I levels of 170 ng/mL), steep declines and steep increases in trajectory slope (HR 2.22, 1.30-3.80 for a 15% decline; HR 1.40, 1.07-1.84 for a 10% decline; HR 1.80, 1.12-2.89 for a 15% increase; HR 1.31, 1.00-1.72 for a 10% increase, each vs no change), and variability ≥10% (HR 1.59, 1.09-2.32 for ≥ 30%; HR 1.36, 1.06-1.75 for 20%; and HR 1.17, 1.03-1.32 for 10% variability, each vs 0%) in IGF-I levels were independently associated with mortality. Conclusions In contrast to data from animal models, low IGF-I levels are associated with higher mortality in older humans. Irrespective of the actual IGF-I level, older individuals with stability of IGF-I levels have lower mortality than those whose IGF-I levels fluctuate over time.

AB - Background Disruption of insulin-like growth factor-I (IGF-I) increases health and life span in animal models, though this is unconfirmed in humans. If IGF-I stability indicates homeostasis, the absolute level of IGF-I may be less clinically relevant than maintaining an IGF-I setpoint. Methods Participants were 945 U.S. community-dwelling individuals aged ≥65 years enrolled in the Cardiovascular Health Study with IGF-I levels at 3-6 timepoints. We examined the association of baseline IGF-I level, trajectory slope, and variability around the trajectory with mortality. Results There were 633 deaths over median 11.3 years of follow-up. Lower IGF-I levels, declining or increasing slope, and increasing variability were each individually associated with higher mortality (all p <.001). In an adjusted model including all three trajectory parameters, baseline IGF-I levels <70 ng/mL (hazard ratio [HR] 1.58, 95% CI 1.28-1.96 relative to IGF-I levels of 170 ng/mL), steep declines and steep increases in trajectory slope (HR 2.22, 1.30-3.80 for a 15% decline; HR 1.40, 1.07-1.84 for a 10% decline; HR 1.80, 1.12-2.89 for a 15% increase; HR 1.31, 1.00-1.72 for a 10% increase, each vs no change), and variability ≥10% (HR 1.59, 1.09-2.32 for ≥ 30%; HR 1.36, 1.06-1.75 for 20%; and HR 1.17, 1.03-1.32 for 10% variability, each vs 0%) in IGF-I levels were independently associated with mortality. Conclusions In contrast to data from animal models, low IGF-I levels are associated with higher mortality in older humans. Irrespective of the actual IGF-I level, older individuals with stability of IGF-I levels have lower mortality than those whose IGF-I levels fluctuate over time.

KW - Aging

KW - Insulin like growth factor

KW - Longevity

KW - Longitudinal

KW - Trajectory

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