MITOGENIC FACTORS ACCELERATE LATER-AGE DISEASES - INSULIN AS A PARADIGM

Some genes are expressed differently in earlier and later generations of most cell lines. Many diseases become clinically expressed only lat er in life, and show clustering of the age at onset in the affected si blings, which may be related to the changing expression with age of th e genes involved. Because insulin and its receptor are extremely ancie nt and well preserved structures with almost universal mitogenic effec ts, insulin may serve a paradigm of this process. It is suggested that by stimulating cell proliferation, hyperinsulinemia speeds up the app earance of later generations of cells with different expression of the genes. Insulin resistance, accompanying any hyperinsulinemia and cons idered to be a pathogenetic factor of some common later-age diseases, involves only some biochemical, but not mitogenic effects of the hormo ne. In humans, high levels of insulin in blood are encountered both ph ysiologically after meals and in many pathological conditions: insulin therapy inevitably causes peripheral hyperinsulinemia; in type 2 diab etes hyperinsulinemia precedes hyperglycemia by many years; hyperinsul inemia is an independent risk factor of atherosclerosis, of type 2 dia betes itself, of some forms of dementia and other diseases; obesity is an obligatory hyperinsulinemic condition. The opposite of hyperalimen tation, i.e. calorie restriction (at least, in rodents) may exert its life-prolonging effects through decreasing insulinemia and therefore t he rate of cell proliferation. Insulin is only one example, and differ ent mitogens regulate proliferation of different cells. It is likely t hat growth factors in general accelerating the replication of cells, p lay a role in speeding up the appearance of later-age diseases involvi ng these cells. (C) 1998 Elsevier Science Ireland Ltd. All rights rese rved.