Insulin-like growth factor I and interleukin-6 contribute synergistically to disability and mortality in older women

The physiology of age-related functional decline is poorly understood, but may involve hormones and inflammation. We hypothesized that older women with both low IGF-I and high IL-6 levels are at high risk for disability and death. We assessed walking speed and disability in 718 women enrolled in the Women's Health and Aging Study I, a 3-yr cohort study with 5-yr mortality follow-up. Women with IGF-I levels in the lowest quartile and IL-6 levels in the highest quartile had significantly greater limitation in walking and disability in mobility tasks and instrumental activities of daily living than those with neither risk factor ( adjusted odds ratios, 10.77, 5.14, and 3.66). Women with both risk factors were at greater risk for death ( adjusted relative risk, 2.10) as well as incident walking limitation, mobility disability, and disability in activities of daily living compared with those with high IGF-I and low IL-6 levels. The combination of low IGF-I and high IL-6 levels confers a high risk for progressive disability and death in older women, suggesting an aggregate effect of dysregulation in endocrine and immune systems. The joint effects of IGF-I and IL-6 may be important targets for treatments to prevent or minimize disability associated with aging.