Insulin/IGF-1 signaling pathway driving aging and cancer as a target for pharmacological intervention.
Studies in mammals have led to the suggestion that hyperglycemia and hyperinsulinemia are important factors both in aging and in the development of cancer. Insulin/insulin-like growth factor 1 (IGF-1) signaling molecules that have been linked to longevity include DAF-2 and InR and their homologues in mammals, and inactivation of the corresponding genes followed by the increase in life span in nematodes, fruit flies and mice. It is possible that the life-prolonging effect of calorie restriction is due to decreasing IGF-1 levels. A search of pharmacological modulators of insulin/IGF-1 signaling pathway mimetic effects of life span extending mutations or calorie restriction could be a perspective direction in regulation of longevity. Some old and new observations suggest that antidiabetic biguanides could be promising candidates for both the life span extension and the prevention of cancer.
Anisimov
Vladimir N
VN
Department of Carcinogenesis and Oncogerontology, N.N. Petrov Research Institute of Oncology, Pesochny-2, St Petersburg 197758, Russian Federation. aging@mail.ru
D000375:Aging / Q000502:physiology*; D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D008136:Longevity / Q000187:drug effects; D009369:Neoplasms / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology
D001645:Biguanides; D007328:Insulin; D007334:Insulin-Like Growth Factor I