Role of the IGF/insulin system in longevity.
Human life expectancy is influenced by multiple determinants, including various environmental and genetic factors. Though the non-genetic factors are important, it is estimated that approximately 25-32% of the overall difference in human lifespan for survival after the age of 60 years depends on for by genetic polymorphisms among individuals. In addition, there are human homologues to many genes that affect lifespan in model organisms. In people, longevity genes might slow the rate of age-related changes in cells, increase resistance to environmental stresses like infection and injury, and reduce the risk of many age-related conditions. The best studied longevity pathway is probably the one involving insulin/IGF-1 signaling. The important role of IGF and insulin-related signaling pathways in the control of longevity of worms and insects is very well documented. In the mouse, several spontaneous or experimentally induced mutations that interfere with GH/IGF axis modulation lead to extended longevity. Increases in the average life span in these mutants range from approximately 20-70% depending on the nature of the endocrine defect, gender, diet, and/or genetic background. All the data in animals models and in the population studies support the evidence that this pathway drives an evolutionarily conserved network that regulates lifespan and affects longevity across species. Results obtained in humans are still controversial and further extensive studies are required to firmly establish a role of the IGF1 axis in modulation of human longevity. A better knowledge of the role of this pathway in humans may assist in the design of improved treatment methods for age-related diseases, delay the aging process and prolong the human lifespan.
Department of Medical Sciences, University of Milan, Milan, Italy. daniela.mari@unimi.it
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D000818:Animals; D013006:Growth Hormone / Q000235:genetics; D006801:Humans; D007004:Hypoglycemic Agents; D007328:Insulin / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008136:Longevity / Q000235:genetics*; D011110:Polymorphism, Genetic; D015398:Signal Transduction
D007004:Hypoglycemic Agents; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone