Oxidative Aging and Insulin Receptor Signaling

The life span of nematodes, fruit flies, and mice can be significantly increased (and aging-related changes decreased) by mutations affecting insulin receptor signaling. This effect involves several cellular functions which are negatively regulated by the insulin receptor and thus typically expressed under fasting conditions. This involvement raises the question of whether the insulin-independent basal receptor kinase activity in the postabsorptive state can be decreased without compromising the physiologically important response to insulin in the postprandial state. Recent studies have shown that (a) the basal human insulin receptor kinase activity is increased under oxidative conditions in the absence of insulin and (b) insulin signaling in the fasted state can be decreased by cysteine supplementation. Cysteine supplementation has also been shown to improve certain aging-related parameters, suggesting that the average dietary cysteine consumption in Western countries may be suboptimal. These findings provide a conceptual framework that extends the "free radical theory of aging."