Clinical study
Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham Heart Study

https://doi.org/10.1016/j.amjmed.2003.05.001Get rights and content

Abstract

Background

Aging is associated with increased production of catabolic cytokines, reduced circulating levels of insulin-like growth factor 1 (IGF-1), and acceleration of sarcopenia (loss of muscle with age). We hypothesized that these factors are independently linked to mortality in community-dwelling older persons.

Methods

We examined the relation of all-cause mortality to peripheral blood mononuclear cell production of inflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin 1β, interleukin 6), serum interleukin 6 and IGF-1, and fat-free mass and clinical status in 525 ambulatory, free-living participants in the Framingham Heart Study.

Results

Of the 525 subjects (aged 72 to 92 years at baseline), 122 (23%) died during 4 years of follow-up. After adjusting for age, sex, comorbid conditions, smoking, and body mass index, mortality was associated with greater cellular production of TNF-α (hazard ratio [HR] = 1.27 per log10 difference in ng/mL; 95% confidence interval [CI]: 1.00 to 1.61; P = 0.05) and higher serum interleukin 6 levels (HR = 1.30 per log10 difference in pg/mL; 95% CI: 1.04 to 1.63]; P = 0.02), but not with higher serum IGF-1 levels (HR = 0.70 per log10 difference in pg/mL; 95% CI: 0.49 to 0.99; P = 0.04). In a subset of 398 subjects (55 deaths) in whom change in fat-free mass index during the first 2 years was measured, less loss of fat-free mass and greater IGF-1 levels were associated with reduced mortality during the next 2 years.

Conclusion

Greater levels or production of the catabolic cytokines TNF-α and interleukin 6 are associated with increased mortality in community-dwelling elderly adults, whereas IGF-1 levels had the opposite effect.

Section snippets

Subjects

The Framingham Heart Study, a population-based cohort examined biennially since 1948, originally comprised 5209 men and women aged 30 to 62 years. During 1992 to 1994, 1166 participants were still alive and 940 attended the 22nd clinic examination. Analyses of cytokines and IGF-1 were carried out in a subsample of 780 participants using blood collected at this examination. The 525 persons whose vital status was known at Examinations 22 through 24, and on whom there were complete data on all

Results

Of 732 possible observations, complete data were available in 525 participants (Table 1). All subjects were living in the community and participated in Examination 22. Although subjects who were excluded and those who were included were similar regarding potential confounding variables and mortality, there were differences for log-stimulated TNF-α (using 1 ng/mL or 100 ng/mL of lipopolysaccharide) and log spontaneous interleukin 1 receptor antagonist. However, none of these variables were

Discussion

We hypothesized that subclinical inflammation, via higher levels of catabolic cytokines, especially interleukin 6, and lower levels of the anabolic factor IGF-1, would accelerate sarcopenia and mortality in the elderly. Our results indicate that cellular production of TNF-α, circulating interleukin 6, and circulating IGF-1 are associated with mortality in a cohort of community-dwelling elderly adults, after adjustment for important clinical conditions, body mass index, and smoking. Moreover,

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    Supported by NIH/USDA Interagency Agreement AG-4-0245 (RR); NIH grants DK02120 (RR), AG15797 (RR), and AI-15614 (CAD); NHLBI Contract N01-HC-38038; and USDA Cooperative Agreement 58-1950-9-001. The content of this publication does not necessarily reflect the views or policies of the United States Department of Agriculture or Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government.

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