Central and peripheral effects of insulin/IGF-1 signaling in aging and cancer: antidiabetic drugs as geroprotectors and anticarcinogens.
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 linked to longevity include DAF-2 and insulin receptor (InR) and their homologues in mammals and to inactivation of the corresponding genes followed by increased life span in nematodes, fruit flies, and mice. It is possible that the life-prolonging effect of caloric restriction are due to decreasing IGF-1 levels. A search of pharmacological modulators of life span-extending mutations in the insulin/IGF-1 signaling pathway and mimetics of effects of caloric restriction could be a direction in the regulation of longevity. Some literature and our own observations suggest that antidiabetic drugs could be promising candidates for both life span extension and prevention of cancer.
Anisimov
Vladimir N
VN
N.N. Petrov Research Institute of Oncology, St. Petersburg 197758, Russia. aging@mail.ru
Berstein
Lev M
LM
Popovich
Irina G
IG
Zabezhinski
Mark A
MA
Egormin
Peter A
PA
Tyndyk
Margarita L
ML
Anikin
Ivan V
IV
Semenchenko
Anna V
AV
Yashin
Anatoli I
AI
D000375:Aging / Q000502:physiology*; D000818:Animals; D001645:Biguanides / Q000378:metabolism / Q000627:therapeutic use; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D031204:Caloric Restriction; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D001645:Biguanides; D029742:Caenorhabditis elegans Proteins; D007004:Hypoglycemic Agents; D007328:Insulin; D007334:Insulin-Like Growth Factor I; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin