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  • Title: Mitogenic factors accelerate later-age diseases: insulin as a paradigm.
    Author: Lev-Ran A.
    Journal: Mech Ageing Dev; 1998 May 01; 102(1):95-113. PubMed ID: 9663795.
    Abstract:
    Some genes are expressed differently in earlier and later generations of most cell lines. Many diseases become clinically expressed only later in life, and show clustering of the age at onset in the affected siblings, which may be related to the changing expression with age of the genes involved. Because insulin and its receptor are extremely ancient and well preserved structures with almost universal mitogenic effects, insulin may serve a paradigm of this process. It is suggested that by stimulating cell proliferation, hyperinsulinemia speeds up the appearance of later generations of cells with different expression of the genes. Insulin resistance, accompanying any hyperinsulinemia and considered to be a pathogenetic factor of some common later-age diseases, involves only some biochemical, but not mitogenic effects of the hormone. In humans, high levels of insulin in blood are encountered both physiologically after meals and in many pathological conditions: insulin therapy inevitably causes peripheral hyperinsulinemia; in type 2 diabetes hyperinsulinemia precedes hyperglycemia by many years; hyperinsulinemia is an independent risk factor of atherosclerosis, of type 2 diabetes itself, of some forms of dementia and other diseases; obesity is an obligatory hyperinsulinemic condition. The opposite of hyperalimentation, i.e. calorie restriction (at least, in rodents) may exert its life-prolonging effects through decreasing insulinemia and therefore the rate of cell proliferation. Insulin is only one example, and different mitogens regulate proliferation of different cells. It is likely that growth factors in general accelerating the replication of cells, play a role in speeding up the appearance of later-age diseases involving these cells.
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