Control of aging and longevity by IGF-I signaling.

Animal models have established the IGF-I signaling pathway as a key modulator of aging in rodents and invertebrates. Considerable evidence suggests that reduced exposure of tissue to IGF-I is associated with an extended lifespan in these species. In humans, IGF-I is linked to various age-related diseases that are limiting factors for youthful longevity. On one hand, reduced IGF-I activity is associated with significant morbidity in adulthood with an increased risk of developing cardiovascular disease, diabetes, osteoporosis and neurodegenerative diseases. On the other hand, elevated IGF-I levels have been linked to cancer risk given the role of IGF in mediating normal and malignant tissue growth. Thus, IGF is clearly involved in modulating disease of aging; however, the mechanism appears to be complex and interdependent on additional modulating factors. It is attractive to hypothesize that maximal human survival depends on tight regulation of the GH-IGF axis and maintenance of optimal IGF-I action in order to prevent morbidities associated with either deficient or excessive state. Specifically, it is possible that lower levels of IGF-I during early adulthood followed by higher levels of IGF-I later in life may be most beneficial for human longevity by addressing age-specific morbidities.