Life span extension and cancer risk: myths and reality.
A significant increase in the number of old people in the populations of developed countries was followed by an increase in morbidity and mortality resulting from main age-related diseases -- cardiovascular, cancer, neurodegenerative, diabetes mellitus, decrease in resistance to infections. Obviously, the development of the means of prevention of the premature aging of humans is crucial for the realization of this program. However, data available on such kind of means are rather scarce, contradictory and are often not reliable from the points of view of the adequacy of the experiments to current scientific requirements as well as the interpretation of the results and safety. Data available on the increase in life span and the adverse effects of the following geroprotectors were critically analyzed: antioxidants, chelate agents and lathyrogens, succinate, adaptogens and herbs, neurotropic drugs, inhibitors of monoamine oxidase, glucocorticoids, dehydroepiandrosterone, sex and growth hormones, melatonin, pineal peptide preparations, protein inhibitors, antidiabetic biguanides, thymic hormones and peptides, immunomodulators, enteroadsorbents, lypofuscin inhibitors, as well as calorie intake restriction and special diets. Most of the available results were insufficient and could not provide convincing evidence for the life span extension and the safety of the suggested geroprotectors. Drugs and means prolonging the life span could be subdivided into three groups: (a) geroprotectors prolonging the life span equally in all the members of the population: these postponed the beginning of the population's aging; (b) geroprotectors decreasing the mortality rate in a long-lived subpopulation, which raised their maximal life span: these slowed down the population's aging rate; (c) geroprotectors increasing the survival rate in a short-lived subpopulation without changes in the maximal life span: in this case, the aging rate increased. There was a high positive correlation between the type of geroprotector-induced aging delay and the pattern of tumour development in the same population of animals. The first type of geroprotectors did not influence the incidence of tumour but increased tumour latency. The second type of geroprotectors was effective both in the inhibition of spontaneous carcinogenesis and the increase in tumour latency. Certain drugs of the third type raised tumour incidence in the exposed populations. According to the multistage model, geroprotectors either inhibit or accelerate the passage of carcinogen-exposed cells form one stage to another. Thus, the efficacy of geroprotectors as preventive means of cancer development will decrease with respect to the age of exposure onset. Recommendations of the available drugs and means of life span increase should be carefully reconsidered under the international scientific control.
Anisimov
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Laboratory of Carcinogenesis and Aging, Department of Carcinogenesis and Oncogerontology, N.N. Petrov Research Institute of Oncology, Pesochny-2, 68 Leningradskaya Street, 197758 St. Petersburg , Russian Federation. aging@mail.ru
D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D000302:Adrenal Cortex / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D003270:Contraceptive Agents / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D003432:Cross-Linking Reagents; D002149:Energy Intake; D012739:Gonadal Steroid Hormones / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D013006:Growth Hormone / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D015994:Incidence; D008017:Life Expectancy; D008136:Longevity / Q000187:drug effects*; D008550:Melatonin / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D009369:Neoplasms / Q000453:epidemiology*; D018377:Neurotransmitter Agents / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D010870:Pineal Gland / Q000378:metabolism; D012307:Risk Factors; D013963:Thyroid Hormones / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000975:Antioxidants; D003270:Contraceptive Agents; D003432:Cross-Linking Reagents; D012739:Gonadal Steroid Hormones; D007004:Hypoglycemic Agents; D018377:Neurotransmitter Agents; D013963:Thyroid Hormones; D013006:Growth Hormone; D008550:Melatonin