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.
Yang
Joshua
J
Division of Pediatric Endocrinology, Mattel Children's Hospital at UCLA, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
Anzo
Makoto
M
Cohen
Pinchas
P
D000375:Aging / Q000502:physiology*; D000818:Animals; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008136:Longevity / Q000502:physiology*; D008931:Mitochondria, Muscle / Q000378:metabolism; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D045222:Electron Transport Chain Complex Proteins; D007334:Insulin-Like Growth Factor I