Possible beneficial role of exercise in modulating low-grade inflammation in the elderly.

Aging is associated with increased levels of tumor necrosis factor-alpha (TNF) and interleukin (IL)-6. These two cytokines are tightly linked in that TNF induces production of IL-6, which again inhibits TNF gene expression. In epidemiological studies, both cytokines have been associated with obesity, insulin resistance and atherosclerosis. However, based on basal studies, we suggest that TNF (and not IL-6) is the driver behind insulin resistancy. Thus, it is possible that selective enhancement of the IL-6 level may inhibit TNF-induced insulin resistance. Muscle contractions induce production and release of IL-6, but not TNF, into the circulation, in both young and elderly humans. We suggest that muscle-derived IL-6 contributes to mediate the beneficial metabolic effects of exercise and may contribute to inhibit TNF-production and thereby insulin resistance.