Buscar en
Revista Española de Geriatría y Gerontología
Toda la web
Inicio Revista Española de Geriatría y Gerontología Investigación experimental sobre envejecimiento: el falso conocimiento a la ver...
Información de la revista
Vol. 39. Núm. 5.
Páginas 320-328 (Enero 2004)
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Vol. 39. Núm. 5.
Páginas 320-328 (Enero 2004)
Acceso a texto completo
Investigación experimental sobre envejecimiento: el falso conocimiento a la verdadera ignorancia
Experimental ageing research: from false knowledge to true ignorance
Visitas
9633
V.N. Anisimov
Autor para correspondencia
aging@mail.ru

Correspondencia: Departamento de Carcinogénesis y Oncogerontología. Instituto de Investigación Oncológica N.N. Petrov. Pesochny-2. 197758 San Petersburgo. Rusia.
Departamento de Carcinogénesis y Oncogerontología. Instituto de Investigación Oncológica N.N. Petrov. San Petersburgo. Rusia
Este artículo ha recibido
Información del artículo
Resumen

Este trabajo revisa varios «puntos conflictivos» de la gerontología actual, como la búsqueda de los genes de la longevidad, el papel en el envejecimiento del estrés oxidativo y el de las vías de señalización de insulina IGF-1, la participación en el envejecimiento celular y el cáncer de los telómeros y las telomerasas, y la función de la glándula pineal en el proceso de envejecimiento y el cáncer. Se ha publicado en los últimos años una gran cantidad de artículos y excelentes documentos de investigación sobre estos temas. Creemos que el entusiasmo que han provocado los nuevos descubrimientos debe ser compensado por un sano escepticismo, como indica el sofisma de Sócrates: cuando aumenta nuestro conocimiento, obligatoriamente aumenta nuestro desconocimiento.

Palabras clave:
Gerontología actual
Genes de la longevidad
Envejecimiento del estrés oxidativo
Abstract

The present study reviews several controversial areas of current gerontology, such as the search for longevity genes, the role of oxidative stress in ageing and that of insulin/insulin-like growth factor-1 (IGF-1) signalling pathways, the contribution of telomeres and telomerases in cellular ageing and cancer, and the function of the pineal gland in the process of ageing and cancer. In the last few years, a large number of articles and high-quality research studies have been published on these subjects. We believe that theenthusiasm stimulated by these new findings should be counterbalanced by healthy scepticism, as expressed by Socrates' sophism: as our knowledge increases, so necessarily does our lack of knowledge.

Key words:
Current gerontology
Longevity genes
Oxidative stress ageing
El Texto completo está disponible en PDF
Bibliografía
[1.]
C.E. Finch, G. Ruvkun.
The genetics of aging.
Ann Rev Genomics Hum Genet, 2 (2001), pp. 435-462
[2.]
R.N. Butler, M. Fossel, S.M. Harman, et al.
Is there an antiaging medicine?.
J Gerontol Biol Sci, 57 (2002), pp. B333-B338
[3.]
P. Hasty, J. Campisi, J. Hoeijmakers, et al.
Aging and genome maintenance: lessons from the mouse?.
Science, 299 (2003), pp. 1355-1359
[4.]
V.N. Anisimov.
Aging and cancer in transgenic and mutant mice.
Front Biosci, 8 (2003), pp. S883-S902
[5.]
H. Liang, E.J. Masoro, J.F. Nelson, et al.
Genetic mouse models of extended lifespan.
Exp Gerontol, 38 (2003), pp. 1353-1364
[6.]
V.N. Anisimov.
Carcinogenesis and aging. Vols 1 and 2.
[7.]
V.N. Anisimov.
The relationship between aging and carcinogenesis.
Crit Rev Oncol Hematol, 45 (2003), pp. 277-304
[8.]
B.N. Ames, M.B. Shigenaga, T.M. Hagen.
Oxidants, antioxidants, and the degenerative diseases of aging.
Proc Natl Acad Sci USA, 90 (1993), pp. 7915-7922
[9.]
D. Harman.
Extending functional life span.
Exp Gerontol, 33 (1998), pp. 95-112
[10.]
V.P. Skulachev.
The programmed death phenomena, aging, and the Samurai law of biology.
Exp Gerontol, 36 (2001), pp. 995-1024
[11.]
R. Cutler.
Oxidative stress: its potential relevance to human disease and longevity determinants.
Age, 18 (1995), pp. 91-96
[12.]
R. Arking, A.G. Force, S.P. Dugas, et al.
Factors contributing to the plasticity of the extended longevity phenotypes of Drosophila.
Exp Gerontol, 31 (1996), pp. 623-643
[13.]
W.C. Orr, R.S. Sohal.
Extension of life-span by overexpresion of superoxide dismutase and catalase in Drosophila melanogaster.
Science, 263 (1994), pp. 1128-1130
[14.]
T.L. Parkes, A.J. Elia, D. Dickinson, et al.
Extension of Drosophila lifespan by overexpression of human SOD1 in motoneurons.
Nature Genetics, 19 (1998), pp. 171-174
[15.]
S. Melov, J. Ravenscroft, S. Malik, et al.
Extension of life-span with superoxide dismutase/catalase mimetics.
Science, 289 (2000), pp. 1567-1569
[16.]
T.T. Huang, E.J. Carlson, A.M. Gillespie, et al.
Ubiquitous overexpression of CuZn superoxide dismutase does not extend life span in mice.
J Gerontol A Biol Sci Med Sci, 55 (2000), pp. B5-B9
[17.]
H. Babich.
Butylated hydroxytoluene (BHT): a review.
Environ Res, 29 (1982), pp. 1-29
[18.]
N. Ito, M. Hirose.
The role of antioxidants in chemical carcinogenesis.
Jpn J Cancer Res, 78 (1987), pp. 1011-1026
[19.]
M.M. Manson, J.A. Green, H.E. Driver.
Ethoxyquin alone inducespreneoplastic changes in rat kidney whilst preventing induction of such lesions in liver by aflatoxin B(1).
Carcinogenesis, 8 (1987), pp. 723-728
[20.]
E.A. Porta, N.S. Joun, R.T. Nitta.
Effect of the type of dietary fat at two levels of vitamin E in Wistar male rats during development and aging. I. Life span, serum biochemical parameters and pathological changes.
Mech Ageing Dev, 13 (1980), pp. 1-39
[21.]
B. Toth, K. Patil.
Enhancing effect of vitamin E on murine intestinal tumorigenesis by 1,2-dimethylhydrazine dihydrochloride.
J Natl Cancer Inst, 70 (1983), pp. 1107-1111
[22.]
M. Ohshima, J.M. Ward, M.L. Wenk.
Preventive and enhancing effects of retinoids on the development of naturally occuring tumors of skin, prostate gland, and endocrine pancreas in aged male ACI/segHapBR rats.
J Natl Cancer Inst, 74 (1985), pp. 517-524
[23.]
H.A. Schroeder, M. Mitchener.
Selenium and tellurium in rats: effect on growth, survival and tumors.
J Nutr, 101 (1971), pp. 1531-1540
[24.]
L.A. Cherkes, S.G. Aptekar, M.N. Volgarev.
Liver tumors induced by selenium.
Bull Exp Biol Med, 53 (1962), pp. 78-83
[25.]
M.R. McCall, B. Frei.
Can antioxidant vitamins meterially reduce oxidative damage in humans?.
Free Radical Biol Med, 26 (1999), pp. 1034-1053
[26.]
A. Bartke, V. Chandrashekar, F. Dominici, et al.
Insulin-like growth factor 1 (IGF01) and aging: controvrses and new insights.
Biogerontology, 4 (2003), pp. 1-8
[27.]
M. Tatar, A. Bartke, A. Antebi.
The endocrine regulation of afging by insulin-like signals.
Science, 299 (2003), pp. 1346-1351
[28.]
F.S. Facchini, N.W. Hua, G.M. Reaven, R.A. Stoohs.
Hyperinsulinemia: the missing link among oxidative stress and age-related diseases?.
Free Radicals Biol Med, 29 (2000), pp. 1302-1306
[29.]
V.M. Dilman.
Development, aging and disease. A new rationale for an intervention.
Harwood Academic Publ, Chur, (1994),
[30.]
M. Barbieri, M.R. Rizzo, D. Manzella, et al.
Glucose regulation and oxidative stress in healthy centenarians.
Exp Gerontol, 38 (2003), pp. 137-143
[31.]
L.A. Colangelo, S.M. Gapstur, P.H. Gann.
Colorectal cancer mortality and factors related to the insulin resistance syndrome.
Cancer Epidemiol Biomarkers Prev, 11 (2002), pp. 385-391
[32.]
K. Gupta, G. Krishnaswamy, A. Karnad, A.N. Peiris.
Insulin: a novel factor in carcinogenesis.
Am J Med Sci, 323 (2002), pp. 140-145
[33.]
V.D. Longo, C.E. Finch.
Evolutionary medicine: from dwarf model systems to healthy centenarians?.
Science, 299 (2003), pp. 1342-1346
[34.]
Masoro EJ. Subfield history: caloric restriction, slowing aging, and extending life. Science's SAGE KE, 2003, ns2 [consultado 26/7/2003). Disponible e: http://Sageke.sciencemag.org/cgi/content/full/sageke;2003/8/re2
[35.]
E.C. Hadley, C. Dutta, J. Finkelstein, et al.
Human implications of caloric restriction's effect on laboratory animals: an overview of opportunities for research.
J Gerontol Ser A, 56A (2001), pp. 5-6
[36.]
R. Weindruch, K.P. Keenan, J.M. Carney, et al.
Caloric restriction mimetics: metabolic intervention.
J Gerontol Biol Sci, 56A (2001), pp. 20-33
[37.]
S. Muntoni.
Metformin and fatty acids.
Diabetes Care, 22 (1999), pp. 179-180
[38.]
L.M. Berstein, T.P. Evtushenko, E.V. Tsyrlina, et al.
Comparative study of 5-and 10-year-long results of the metabolic rehabilitation of cancer patients.
editors. Neuroendocrine system, metabolism, immunity and cancer (clinical aspects), pp. 102-112
[39.]
V.V. Bakaev.
Effect of 1-butylbiguanide hydrochloride on the longevity in the nematoda Caenorhabditis elegans.
Biogerontology, 3 (2002), pp. 23-24
[40.]
V.N. Anisimov, A.V. Semenchenko, A.I. Yashin.
Insulin and longevity: antidiabetic biguanides as geroprotectors.
Biogerontology, 4 (2003), pp. 297-307
[41.]
K.A. Awartani, A.P. Cheung.
Metformin and polycystic ovary syndrome: a literature review.
J Obstet Gynecol Can, 24 (2002), pp. 393-401
[42.]
M.L. Fernandes, M.J. Saad, L.A. Velloso.
Effect of age on elements of insulinsignaling pathway in central nervous system of rats.
Endocrine, 16 (2001), pp. 227-234
[43.]
J.S. Richards, D.L. Russell, S. Ochsner, et al.
Novel signaling pathways that control ovarian follicular development, ovulation, and luteinization.
Recent Prog Horm Res, 57 (2002), pp. 195-220
[44.]
T. Chiba, H. Yamaza, Y. Higami, I. Shimokawa.
Anti-aging effects of caloric restriction: Involvement of neuroendocrine adaptation by peripheral signaling.
Microsc Res Tech, 59 (2002), pp. 317-324
[45.]
M.P. Mattson, W. Duan, N. Maswood.
How does the brain control lifespan?.
Ageing Res Rev, 1 (2002), pp. 155-165
[46.]
V.N. Anisimov.
Insulin: IGF-1 signaling pathway driving aging and cancer as a target for pharmacological intervention.
Exp Gerontol, 38 (2003), pp. 1041-1049
[47.]
P. Gargiulo, D. Caccese, P. Pignatelli, et al.
Metformin decreases platelet superoxide anion production in diabetic patients.
Diabetes Metab Res Rev, 18 (2002), pp. 156-159
[48.]
J. Campisi.
Cellular senescence and apoptosis: how cellular responses might influence aging phenotypes.
Exp Gerontol, 38 (2003), pp. 5-11
[49.]
A. Maciera-Coelho.
Neoplastic disease through the human life span.
Biogerontology, 2 (2001), pp. 179-192
[50.]
A. Maciera-Coelho.
Genome reorganization through cell division, implications for aging of the organism and cancer development.
Ann NY Acad Sci, 719 (1994), pp. 108-128
[51.]
N. Tavoloni, H. Inoue.
Cellular aging is a critical determinant of primary cell resistance to v-src transformation.
J Virol, 71 (1997), pp. 237-247
[52.]
T. Kunisada, D. Danner, V. Friedman, E.L. Schneider.
Incerased susceptibility to SV40 transformation with development and in vitro aging.
Exp Cell Res, 189 (1990), pp. 222-226
[53.]
F. Bringold, M. Serrano.
Tumor supressors and oncogenes in cellular senescence.
Exp Gerontol, 35 (2000), pp. 317-329
[54.]
J.W. Shay, W.E. Wright, H. Werbin.
Loss of telomeric DNA during aging may predispose cells to cancer.
Int J Oncology, 3 (1993), pp. 559-563
[55.]
R.R. Reddel.
A reassessment of the telomere hypothesis of senescence.
[56.]
M.V. Blagosklonny.
How carcinogens (or telomere dysfunction) induce genetic instability: associated-selection model.
FEBS Lett, 506 (2001), pp. 169-172
[57.]
D. Wynford-Thomas, J.A. Bond, F.S. Wyllie, C.J. Jones.
Does telomere shortening drive selection for p53 mutation in human cancer?.
Mol Carcinogenesis, 12 (1995), pp. 119-123
[58.]
A. Krtolica, S. Parinello, S. Locckett, et al.
Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging.
Proc Natl Acad Sci USA, 98 (2001), pp. 12072-12077
[59.]
C.A. Rinehart, V.R. Torti.
Aging and cancer: the role of stromal interactions with epithelial cells.
Mol Carcinogenesis, 18 (1997), pp. 187-192
[60.]
N.F. Mathon, D.S. Malcolm, M.C. Harrisingh, et al.
Lack of replicative senescence in normal rodent glia.
Science, 291 (2001), pp. 872-875
[61.]
D.G. Tang, Y.M. Tokumoto, J.A. Apperly, et al.
Lack of replicative senescence in cultured rat oligodendrocyte precursor cell.
Science, 291 (2001), pp. 868-871
[62.]
S.R. Romanov, B.K. Kozakiewicz, C.R. Holst, et al.
Normal human mammary epithelial cells spontaneously escape senescence and aquire genomic changes.
Nature, 409 (2001), pp. 633-637
[63.]
C.V. Clevenger.
A old epithelial cell never dies, it just agonesces away.
Trends Endocrinol Metab, 12 (2001), pp. 183-184
[64.]
S.Y. Rha.
Changes of telomerase and telomere length in paried normal and cancer tissues of breast.
Int J Oncol, 15 (1999), pp. 839-845
[65.]
V.N. Anisimov, N.V. Zhukovskaya, A.S. Loktionov, et al.
Influence of host age on lung colony forming capacity of injected rat rhabdomyosarcoma cells.
Cancer Lett, 40 (1988), pp. 77-82
[66.]
K.D. McCullough, W.B. Coleman, G.J. Smith, J.W. Grisham.
Age-dependent regulation of the tumorigenic potential of neoplastically transformed rat liver epithelial cells by the liver microenvironment.
Cancer Res, 54 (1994), pp. 3668-3671
[67.]
J. Arendt.
Melatonin and the Mammalian Pineal Gland.
[68.]
P. Pevet, B. Bothorel, H. Slotten, M. Saboureau.
The chronobiotic properties of melatonin.
Cell Tissue Res, 309 (2002), pp. 183-191
[69.]
Y. Touitou.
Human aging and melatonin. Clinical relevance.
Exp Gerontol, 36 (2001), pp. 1083-1100
[70.]
O.J. Malm, O.E. Skaug, P. Lingjaerde.
The effect of pinealectomy on bodily growth.
Acta Endocrinol, 30 (1959), pp. 22-28
[71.]
R.J. Reiter, D.X. Tan, S.J. Kim, et al.
Augmentation of indices of oxidative damage in life-long melatonin-deficient rats.
Mech Ageing Dev, 110 (1999), pp. 157-173
[72.]
W. Pierpaoli, W. Regelson.
Pineal control of aging: effect of melatonin and pineal grafting on aging mice.
Proc Natl Acad Sci USA, 91 (1994), pp. 787-791
[73.]
V.A. Lesnikov, W. Pierpaoli.
Pineal cross-transplantation (old-to-young and vice versa) as evidence for an endogenous «aging clock».
Ann NY Acad Sci, 719 (1994), pp. 461-473
[74.]
V.N. Anisimov.
Effects of exogenous melatonin: a review.
Toxicol Pathol, 31 (2003),
[75.]
S. Cos.
Sánchez-Barceló EJ. Melatonin and mammary pathological growth.
Front Neuroendocrin, 17 (2000), pp. 133-170
[76.]
F. Deerberg, C. Bartsch, G. Pohlmeyer, H. Bartsch.
Effect of melatonin and physiological epiphysectomy on the developmet of spontaneous endometrial carcinoma in BDII/HAN rats.
Cancer Biother Radiopharmacol, 12 (1997), pp. 420
[77.]
V.N. Anisimov, I.G. Popovich, M.A. Zabezhinski.
Melatonin and colon carcinogenesis: I. Inhibitory effects of melatonin on development of intestinal tumors induced by 1,2-dimethylhydrazine in rats.
Carcinogenesis, 18 (1997), pp. 1549-1553
[78.]
V.N. Anisimov, M.A. Zabezhinski, I.G. Popovich, et al.
Inhibitory effect of melatonin on 7,12-dimethylbenz[a]anthracene-induced carcinogenesis of the uterine cervix and vagina in mice and mutagenesis in vitro.
Cancer Lett, 156 (2000), pp. 199-205
[79.]
K. Imaida, A. Hagiwara, H. Yoshino, et al.
Inhibitory effects of low doses of melatonin on induction of preneoplastic liver lesions in a medium-term liver bioassay in F344 rats: relation to the influence of electromagnetic near field exposure.
Cancer Lett, 155 (2000), pp. 105-114
[80.]
P. Lissoni.
Is there a role for melatonin in supportive care?.
Support Care Cancer, 10 (2002), pp. 110-116
[81.]
G. Bellipanni, P. Bianchi, W. Pierpaoli, et al.
Effects of melatonin in perimenopausal and menopausal women: a randomized and placebo controlled study.
Exp Gerontol, 36 (2001), pp. 297-310
[82.]
US General Accounting Office. Anti-aging products pose potential for physical and economic harm. Special Committee on Aging, GAO-01-1129, September 2001. Disponible en: http://aging.senate.gov/hr73gao.pdf
[83.]
V.N. Anisimov.
Life span extension and cancer risk: myths and reality.
Exp Geront, 36 (2001), pp. 1101-1136
[84.]
J.B. Chen, J. Sun, S.M. Jazwinski.
Prolongation of the yeast life span by the v-Ha-RAS oncogene.
Mol Microbiol, 4 (1990), pp. 2081-2086
[85.]
Y.J. Lin, L. Seroude, S. Benzer.
Extended life-span and stress resistance in the Drosophila mutant methuselah.
Science, 282 (1998), pp. 943-946
[86.]
J.Z. Morris, H.A. Tissenbaum, G. Ruvkun.
A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans.
Nature, 382 (1996), pp. 536-539
[87.]
K.D. Kimura, H.A. Tissenbaum, Y. Liu, G. Ruvkun.
daf-2, an insulin receptorlike gene that regulated longevity and diapause in Caenorhabditis elegans.
Science, 277 (1997), pp. 942-946
[88.]
A. Mitsui, J. Hamuro, R. Nakamura, et al.
Overexpression of human thioredoxin in transgenic mice controls oxidative stress and life span.
Antioxid Redox Signal, 4 (2002), pp. 693-696
[89.]
E. Migliaccio, M. Giorgio, S. Mele, et al.
The p66shr adaptor protein controls oxidative stress response and life span in mammals.
Nature, 402 (1999), pp. 309-313
[90.]
M. Holzenberger, J. Dupond, B. Ducos, et al.
IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice.
Nature, 421 (2003), pp. 182-187
[91.]
A.G. Bodnar, M. Ouellette, M. Frolkis, et al.
Extension of life span by introduction of telomerase into normal human cells.
Sciences, 279 (1998), pp. 349-352
Copyright © 2004. Sociedad Española de Geriatría y Gerontología
Opciones de artículo
Herramientas
es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos