Insulin and longevity: antidiabetic biguanides as geroprotectors.
The results of previous experimental studies of effects of antidiabetic biguanides (phenformin and buformin) on life span and spontaneous tumor incidence in mice and rats were recalculated and reanalyzed using standard demographic models of mortality. The chronic treatment of female C3H/Sn mice with phenformin prolonged the mean life span by 21.1% (P < 0.05), the mean life span of the last 10% survivors by 28.4% and the maximum life span by 5.5 months (by 26%) in comparison with the control. The demographic aging rate represented by the estimate of respective Gompertz's parameter decreased by 31.2% and MRDT increased 1.45-fold. The treatment significantly inhibited (4.0-fold, P < 0.01) the incidence of mammary adenocarcinomas in mice. Administration of phenformin to female LIO rats failed to influence the mean life span. At the same time, the mean life span of the last 10% survivors increased by 10.1% (P < 0.05), and maximum life span increased by 3 months (+9.8%). Phenformin attenuated the development of spontaneous tumors in comparison to the control. The treatment of female rats with another antidiabetic biguanide, buformin, slightly increased their mean life span (by 7.3%; P > 0.05). The mean life span of the last 10% survivors increased by 12% (P < 0.05) and the maximum life span increased by 2 months (+5.5%) as compared with controls. The population aging rate decreased by 18.1% (P < 0.05) and MRDT increased 1.22-fold under the influence of buformin (P < 0.05). The total tumor incidence decreased by 49.5% in buformin-treated rats. Both antidiabetic biguanides slightly decreased the body weight, slowed down the age-related decline of the reproductive function in female rats. The results of our experiments provide evidence that antidiabetic biguanides are promising geroprotectors as well as drugs which can be used in 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, Russia. aging@mail.ru
Semenchenko
Anna V
AV
Yashin
Anatoli I
AI
D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002026:Buformin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D008136:Longevity / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D009369:Neoplasms / Q000378:metabolism; D010629:Phenformin / Q000494:pharmacology*; D051381:Rats; D015996:Survival Rate
D007004:Hypoglycemic Agents; D007328:Insulin; D010629:Phenformin; D002026:Buformin