Advertisement

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

      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.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Roubenoff R.
        • Hughes V.
        Sarcopenia.
        J Gerontol. 2000; 55A: M716-M724
        • Harris T.
        • Kiel D.
        • Roubenoff R.
        • et al.
        Association of insulin-like growth factor-1 with body composition.
        J Am Geriatr Soc. 1997; 45: 133-139
        • Roubenoff R.
        • Harris T.
        • Abad L.
        • Wilson P.
        • Dallal G.
        • Dinarello C.
        Monocyte cytokine production in an elderly population.
        J Gerontol. 1998; 53A: M20-M26
        • Steel D.
        • Whitehead A.
        The major acute phase reactants.
        Immunol Today. 1994; 15: 81-88
        • Ferrucci L.
        • Harris T.
        • Guralnik J.
        • et al.
        Serum IL-6 level and development of disability in older persons.
        J Am Gerontol Soc. 1999; 47: 639-646
        • Taaffe D.
        • Harris T.
        • Ferrucci L.
        • Rowe J.
        • Seeman T.
        Cross-sectional and prospective relationships of interleukin-6 and C-reactive protein with physical performance in elderly persons.
        J Gerontol. 2000; 55A: M709-M715
        • Volpato S.
        • Guralnik J.
        • Ferrucci L.
        • et al.
        Cardiovascular disease, interleukin-6, and risk of mortality in older women.
        Circulation. 2001; 103: 947-953
        • Harris T.
        • Ferrucci L.
        • Tracy R.
        • et al.
        Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly.
        Am J Med. 1999; 106: 506-512
        • Visser M.
        • Harris T.
        • Langlois J.
        • et al.
        Body fat and skeletal muscle mass in relation to physical disability in very old men and women of the Framingham Heart Study.
        J Gerontol. 1998; 53A: M214-M221
        • Rall L.
        • Rosen C.
        • Dolnikowski G.
        • et al.
        Protein metabolism in rheumatoid arthritis and aging.
        Arthritis Rheum. 1996; 39: 1115-1124
        • Roubenoff R.
        • Dallal G.
        • Wilson P.
        Predicting body fatness.
        Am J Public Health. 1995; 85: 726-728
        • Roubenoff R.
        • Roubenoff R.A.
        • Cannon J.
        • et al.
        Rheumatoid cachexia.
        J Clin Invest. 1994; 93: 2379-2386
        • Taaffe D.
        • Pruitt L.
        • Reim J.
        • Butterfield G.
        • Marcus R.
        Effect of sustained resistance training on basal metabolic rate in older women.
        J Am Geriatr Soc. 1995; 43: 465-471
        • Lindmark E.
        • Diderholm E.
        • Wallentin L.
        • Siegbahn A.
        Relationship between interleukin-6 and mortality in patients with unstable coronary artery disease.
        JAMA. 2001; 286: 2107-2113
        • Beharka A.
        • Meydani M.
        • Wu D.
        • Leka L.
        • Meydani A.
        • Meydani S.
        Interleukin-6 production does not increase with age.
        J Gerontol. 2001; 56A: B81-B88
        • Tilg H.
        • Dinarello C.
        • Mier J.
        Interleukin-6 and APPs.
        Immunol Today. 1997; 18: 428-432
        • Fattori E.
        • Cappelletti M.
        • Costa P.
        • et al.
        Defective inflammatory response in interleukin-6-deficient mice.
        J Exp Med. 1994; 180: 1243-1250
        • Tsujinaka T.
        • Fujita J.
        • Ebisui C.
        • et al.
        Interleukin 6 receptor antibody inhibits muscle atrophy and modulates proteolytic systems in interleukin 6 transgenic mice.
        J Clin Invest. 1996; 97: 244-249
        • Aderka D.
        • Le J.
        • Vilcek J.
        Interleukin-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice.
        J Immunol. 1989; 143: 3517-3522
        • Roubenoff R.
        • Grinspoon S.
        • Skolnik P.
        • et al.
        Role of cytokines and testosterone in regulating lean body mass and resting energy expenditure in HIV-infected men.
        Am J Physiol. 2002; 283: E138-E145
        • Yang S.
        • Alanqeeb M.
        • Simpson H.
        • Goldspink G.
        Cloning and characterization of an IGF-1 isoform expressed in skeletal muscle subjected to stretch.
        J Muscle Res Cell Motil. 1996; 17: 487-495
        • Loughna P.
        • Mason P.
        • Bates P.
        Regulation of insulin-like growth factor-1 gene expression in skeletal muscle.
        Symp Soc Exp Biol. 1992; 46: 319-330
        • Moore L.
        • Pfeffer A.
        • Chie W.
        • et al.
        Induction of an acute phase response in lambs causes an increase in plasma levels of GH and IGF-1.
        J Endocrinol. 1995; 144: 243-250
        • Clemmons D.R.
        • Underwood L.E.
        Nutritional regulation of IGF-1 and IGF binding proteins.
        Annu Rev Nutr. 1991; 11: 393-412
        • Roubenoff R.
        • Baumgartner R.
        • Kiel D.
        • et al.
        Bioelectrical impedance equations in ambulatory elderly Caucasians.
        J Gerontol. 1997; 52: M129-M136
        • Rall L.
        • Roubenoff R.
        • Abad L.
        • Dinarello C.
        • Meydani S.
        The effects of progressive resistance training on immune response in aging and chronic inflammation.
        Med Sci Sports Exerc. 1996; 28: 1356-1365