Topic outline

  • Biogerontología (2011)

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    ingenieria_grafica_-_G709

     

     

    Profesores

    Dámaso Crespo Santiago

    Pedro Reques Velasco

    Manuel I. González-Carreró López

    Carlos Fernández Viadero

     

    Departamento de Anatomía y Biología Celular


    El objetivo de esta asignatura es introducir al estudiante-visitante de esta materia en el apasionante mundo del envejecimiento abordado desde un punto de vista Bio-Psico-Social sin que esta gradación suponga domino de un componente sobre los otros. Por necesidades formativas, nosotros nos centraremos de forma más específica en el área biológica del envejecimiento, es decir en la biogerontología, pero no perderemos el contexto general que nos enmarca y también abordaremos aspectos psicológicos y sociales del envejecimiento (ejemplos concretos los tenemos en el estudio del envejecimiento del sistema nervioso y los aspectos demográficos).
    Pretendemos que el estudiante-visitante se inicie en esta área de conocimiento y la lectura de los temas aquí tratados le sirva para posteriormente abordar con la profundidad que considere oportuno un análisis más pormenorizado si así lo considera. Para intentar conseguir este objetivo, los temas están escritos pensando en estudiante de una facultad de medicina, concretamente de la Universidad de Cantabria, a los cuales les ofrecemos estas materias en forma de asignatura presencial y que tanto éxito ha tenido. En mi nombre y en el de todos los colaboradores que han participado en este proyecto les doy las gracias por su “visita” y esperamos que estén largos ratos entre nosotros.

     

    Palabras Clave de la Asignatura

    Deterioro cognitivo, Demografía del envejecimiento, Envejecimiento celular, Mitocondria, Reparación celular, Biomarcadores del envejecimiento, Envejecimiento humano, Reparación DNA, Radicales libres de oxígeno, Envejecimiento, Biogerontología

  • Bibliografía

      

      

    Capítulo 1. El envejecimiento: definiciones y teorías

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    Capítulo 2. Hominización y longevidad

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    Capítulo 3. El análisis demográfico del envejecimiento: conceptos, técnicas y métodos

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    Capítulo 4. Transición epidemiológica, envejecimiento y territorio

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    • Chesnais, J. C. La transition démographique. Etapes, formes e implications économiques. Étude de series temporelles (1720-1984) relatives a 67 país. PUF, Paris 1986.

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    • Pérez Díaz, J. La situación social de la vejez en España a partir de una perspectiva demográfica (multicopiado) 2004.

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    • Puga González, D. Dependencia y necesidades asistenciales de los mayores en España. Previsión al año 2010. Madrid, Fundación Pfizer, CSIC y Imserso. 2002.

    • Reques, P. y Rodríguez, Población y Territorio en Cantabria, Universidad de Cantabria, Santander, 1997.

    • Reques, P. y Rodríguez, V. Atlas de la población española. Análisis de base municipal. Universidad de Cantabria-CSIC, Banco de Santander y ESRI España, Santander 1998. 

    • Reques, P. “¿Hacia un nuevo orden demográfico internacional?” En: Reques, P. (Coord.) El nuevo orden demográfico. Madrid, Servicios de estudios del BBVA 2002.

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    Capítulo 5. Bases celulares del envejecimiento

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    • Hayflick L. Biología celular del envejecimiento humano. Investigación y Ciencia, 1998, Temas 11:64-72.

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    Capítulo 6. El envejecimiento de los organismos: modelos

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    • Chen C., Contreras R. The bud scar-based screening system for hunting human genes extending life span. Ann. N. Y. Acad. Sci. 2004;1019:355-359.

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    • Guarente L., Picard F. Calorie restriction the SIR2 connection. Cell. 2005;120:473-482.

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    • Imai S., Armstrong C. M., Kaeberlein M., Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000; 403:795-800.

    • Kaeberlein M., Kennedy B. K. Large-scale identification in yeast of conserved ageing genes. Mech. Ageing Dev. 2005;126:17-21.

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    • Kipling D., Davis T., Ostler E. L., Faragher R. G. What can progeroid syndromes tell us about human aging? Science. 2004;305:1426-1431.

    • Laron Z. Do deficiencies in growth hormone and insulin-like growth factor-1 (IGF-1) shorten or prolong longevity? Mech. Ageing Dev. 2005;126:305-307.

    • Liang H, Masoro E. J., Nelson J. F., Strong R., McMahan C. A., Richardson A. Genetic mouse models of extended lifespan. Exp. Gerontol. 2003;38:1353-1364.

    • Lin Y. J., Seroude L., Benzer S. Extended life-span and stress resistance in the Drosophila mutant methuselah. Science. 1998;282:943-946.

    • Longo V. D., Ellerby L. M., Bredesen D. E., Valentine J. S., Gralla E. B. Human Bcl-2 reverses survival defects in yeast lacking superoxide dismutase and delays death of wild-type yeast. J. Cell. Biol. 1997;137:1581-1588.

    • Longo V. D., Finch C. E. Evolutionary medicine: from dwarf model systems to healthy centenarians?. Science. 2003;299:1342-1346.

    • Lutz P. L., Prentice H. M., Milton S. L. Is turtle longevity linked to enhanced mechanisms for surviving brain anoxia and reoxygenation? Exp. Gerontol. 2003;38:797-800.

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    • Minois N. Longevity and aging: beneficial effects of exposure to mild stress. Biogerontology. 2000;1:15-29.

    • Minois N., Frajnt M., Wilson C., Vaupel J. W. Advances in measuring lifespan in the yeast Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA. 2005;102:402-406.

    • Migliaccio E., Giorgio M., Mele S., Pelicci G., Reboldi P., Pandolfi P. P., Lanfrancone L., Pelicci P. G. The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature. 1999;402:309-313.

    • Nystul T. G., Goldmark J. P., Padilla P. A., Roth M. B. Suspended animation in C. elegans requires the spindle checkpoint. Science. 2003;302:1038-1041.

    • Nystul T. G., Roth M. B. Carbon monoxide-induced suspended animation protects against hypoxic damage in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA. 2004;101: 9133-9136.

    • Pandolfi S., Bonafe M., Tella L. D., Tiberi L., Salvioli S., Monti D., Sorbi S., Franceschi C. p66(shc) is highly expressed in fibroblasts from centenarians. Mech. Ageing Dev. 2005;126:839-844.

    • Perls T. T., Wilmoth J., Levenson R., Drinkwater M., Cohen M., Bogan H., Joyce E., Brewster S., Kunkel L., Puca A. Life-long sustained mortality advantage of siblings of centenarians. Proc. Natl. Acad. Sci. USA. 2002;99:8442-8447.

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    Capítulo 7. Daño oxidativo y envejecimiento

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    • Melov S., Ravenscroft J., Malik S., Gill M. S., Walker D. W., Clayton P. E., Wallace D. C., Malfroy B., Doctrow S. R., Lithgow G. J. Extension of life-span with superoxide dismutase/catalase mimetics. Science. 2000;289:1567-1569.

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    Capítulo 8. Daños en el genoma y el envejecimiento

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    • Raha S., Robinson B. H. Mitochondria, oxygen free radicals, disease and ageing. Trends Biochem. Sci. 2000;2510:502-508. 

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    Capítulo 9. Envejecimiento y ritmos biológicos

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    Capítulo 10. Biomarcadores del envejecimiento

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    Capítulo 11. Bases biológicas del binomio envejecimiento-nutrición

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    • Parker B. A., Chapman I. M. Food intake and ageing—the role of the gut. Mech. Ageing Dev. 2004;125:859-866.

    • Poulter N. R., Chang C. L., MacGregor A. J., Snieder H., Spector T. D. Association between birth weight and adult blood pressure in twins: historical cohort study. BMJ. 1999;319:1330-1333.

    • Ramos Cordero P., Nieto López-Guerrero J. La nutrición en el anciano. Requerimientos hídricos. Revista Española de Geriatría y Gerontología. 2005;40(E2):8-12.

    • Reaven G. M. The metabolic syndrome: requiescat in pace. Clin. Chem. 2005;51:931-938.

    • Roberts A., King J., Greenway F. Class III obesity continues to rise in African-American women. Obes. Surg. 2004;14:533-535.

    • Roth G. S., Ingram D. K., Lane M. A. Slowing ageing by caloric restriction. Nat. Med. 1995;1:414-415.

    • Richardson A., Liu F., Adamo M. L., Van Remmen H., Nelson J. F. The role of insulin and insulin-like growth factor-I in mammalian ageing. Best Pract. Res. Clin. Endocrinol. Metab. 2004;18:393-406.

    • Sabate J. The contribution of vegetarian diets to human health. Forum Nutr. 2003;56:218-220.

    • Schmidt-Erfurth U. Nutrition and retina. Dev. Ophthalmol. 2005;38:120-147.

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    • Silventoinen K., Krueger R. F. , Bouchard T. J.  Jr, Kaprio J., McGue M. Heritability of body height and educational attainment in an international context: comparison of adult twins in Minnesota and Finland. Am. J. Hum. Biol. 2004;16:544-555.

    • Sohal R. S. Role of oxidative stress and protein oxidation in the aging process. Free Radic. Biol. Med. 2002;33:37-44.

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    • Tisi D. K., Liu X. J., Wykes L. J., Skinner C. D., Koski K. G. Insulin-like growth factor II and binding proteins 1 and 3 from second trimester human amniotic fluid are associated with infant birth weight. J. Nutr. 2005;135:1667-1672.

    • Ulrich P., Cerami A. Protein glycation, diabetes, and aging. Recent Prog. Horm. Res. 2001;56:1-21.

    • Vinceti M., Wei E. T., Malagoli C., Bergomi M., Vivoli G. Adverse health effects of selenium in humans. Rev. Environ. Health. 2001;16:233-251.

    • Webb A. L., McCullough M. L. Dietary lignans: potential role in cancer prevention. Nutr. Cancer. 2005;51:117-131.

       

    Capítulo 12. Envejecimiento del sistema cardio-vascular

    • Campuzano R., Moya J. L., García-Lledó A., Salido L., Guzmán G., Tomas J. P. Asociación de la disfunción endotelial y el grosor mediointimal carotídeo con los factores de riesgo coronario en pacientes sin evidencia clínica de aterosclerosis. Rev. Esp. Cardiol. 2003;56:546-554.

    • Cheng L., Mantile G., Pauly R., Nater C., Felici A., Monticone R., Bilato C., Gluzband Y. A., Crow M. T. , Stetler-Stevenson W., Capogrossi M. C. Adenovirus-mediated gene transfer of the human tissue inhibitor of metalloproteinase-2 blocks vascular smooth muscle cell invasiveness in vitro and modulates neointimal development in vivo. Circulation. 1998;98:2195-2201.

    • Dart A. M., Kingwell B. A. Pulse pressure: a review of mechanisms and clinical relevance. J. Am. Coll. Cardiol. 2001;37:975-984.

    • De Caterina R., Libby P., Peng H. B., Thannickal V. J., Rajavashisth T. B., Gimbrone M. A. Jr, Shin W. S., Liao J. K. Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J. Clin. Invest. 1995;96:60-68.

    • Fagerberg B., Bondjers L., Nilsson P. Low birth weight in combination with catch-up growth predicts the occurrence of the metabolic syndrome in men at late middle age: the Atherosclerosis and Insulin Resistance study. J. Intern. Med. 2004;256:254-259.

    • Fleg J. L., Shapiro E. P., O’Connor F., Taube J., Goldberg A. P., Lakatta E. G. Left ventricular diastolic filling performance in older male athletes. JAMA. 1995;273:1371-1375.

    • Ford G. A. Ageing and the baroreflex. Age Ageing 1999; 28: 337-338.

    • Gimbrone M. A. Jr. Endothelial dysfunction, hemodynamic forces, and atherosclerosis. Thromb Haemost. 1999;82:722-726.

    • Gerstenblith G., Frederiksen J., Yin F. C., Fortuin N. J., Lakatta E. G., Weisfeldt M. L. Echocardiographic assessment of a normal adult aging population. Circulation. 1977;56:273-278.

    • Hansson G. K. Mechanisms of disease: inflammation, atheosclerosis, and coronary artery disease. New Engl. J. Med. 2005;352:1685-1695.

    • Hernández J. P., Franke W. D. Age- and fitness-related differences in limb venous compliance do not affect tolerance to maximal lower body negative pressure in men and women. J. Appl. Physiol. 2004;97:925-929.

    • Inserra F., Romano L., Ercole L., de Cavanagh E. M., Ferder L. CV changes by long-term inhibition of the renin-angiotensin system in aging. Hypertension. 1995;25:437-442.

    • Jenkins G. M., Crow M. T., Bilato C., Gluzband Y., Ryu W. S., Li Z., Stetler-Stevenson W., Nater C., Froehlich J. P., Lakatta E. G., Cheng L. Increased expression of membrane-type matrix metalloproteinase and preferential localization of matrix metalloproteinase-2 to the neointima of balloon-injured rat carotid arteries. Circulation. 1998;97:82-90.

    • Jialal I., Devaraj S., Venugopal S. K. C-reactive protein: risk marker or mediator in atherothrombosis? Hypertension. 2004;44:6-11.

    • Johnson K. E. CV system. En: Histology and embriology. Johnson K. E. (editor). John Wiley & Sons. New York. 1984;109-118.

    • Kroger K., Ose C., Rudofsky G., Roesener J., Weiland D., Hirche H. Peripheral veins: influence of gender, body mass index, age and varicose veins on cross-sectional area. Vasc. Med. 2003;8:249-255.

    • Lakatta E. G. CV regulatory mechanisms in advanced age. Physiol. Rev. 1993;73:413-465.

    • Lakatta E. G, Levy D. Arterial and cardiac aging: Major Shareholders in CV disease enterprises. Part I: aging arteries: a “set up” for vascular disease. Circulation. 2003;107: 139-146.

    • Lee R. T., Yamamoto C., Feng Y., Potter-Perigo S., Briggs W. H., Landschulz K. T., Turi T. G., Thompson J. F., Libby P., Wight T. N. Mechanical strain induces specific changes in the synthesis and organization of proteoglycans by vascular smooth muscle cells.J. Biol. Chem. 2001;276:13847-13851.

    • Libby P., Ridker P. M., Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105:1135-1143.

    • Matturri L., Ottaviani G., Corti G., Lavezzi A. M. Pathogenesis of early atherosclerotic lesions in infants. Pathol. Res. Pract. 2004;200:403-410.

    • O’Leary D. H., Polak J. F., Kronmal R. A., Manolio T. A., Burke G. L., Wolfson S. K. Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. CV Health Study Collaborative Research Group. N. Engl. J. Med. 1999;340:14-22.

    • Olsen H., Lanne T. Reduced venous compliance in lower limbs of aging humans and its importance for capacitance function. Am. J. Physiol. 1998;275:H878-886.

    • Paciaroni E., Fraticelli A. Left ventricular hypertrophy. Prevalence in older patients and management. Drugs Aging. 1995;6:301-311.

    • Pauly R. R., Passaniti A., Bilato C., Monticone R., Cheng L., Papadopoulos N., Gluzband Y. A., Smith L., Weinstein C., Lakatta E. G. Migration of cultured vascular smooth muscle cells through a basement membrane barrier requires type IV collagenase activity and is inhibited by cellular differentiation. Circ. Res. 1994;75:41-54.

    • Rosei E. A., Muiesan M. L. Early target organ damage and its reversibility: the heart. Clin. Exp. Hypertens. 2004;26:673-687.

    • Sartore S., Chiavegato A., Franch r., Faggin E., Paulette P. Myosin expression and cell phenotypes in vascular smooth muscle during development, in experimental models and in vascular disease. Arterioscler. Thromb. Vasc. Biol. 1997; 17: 1210-1215.

    • Sata M., Saiura A., Kunisato A., Tojo A., Okada S., Tokuhisa T., Hirai H., Makuuchi M., Hirata Y., Nagai R. Hematopoietic stem cells ifferentiate into vascular cells that participate in the pathogenesis of atherosclerosis. Nat. Med. 2002;8:403-409.

    • Shah G. N., Mooradian A. D. Age-related changes in the blood-brain barrier. Exp. Gerontol. 1997;32:501-519.

    • Smit A. A. J., Halliwill J. R., Low P. A., Wielin W. Pathophysiological basis of orthostatic hypotension in autonomic failure. J. Physiol. 1999;519:1-10.

    • Spagnoli L. G., Orlandi A., Mauriello A., Santeusanio G., de Angelis C., Lucreziotti R., Ramacci M. T. Aging and atherosclerosis in the rabbit. 1. Distribution, prevalence and morphology of atherosclerotic lesions. Atherosclerosis. 1991;89:11-24.

    • Taddei S., Virdis A., Mattei P., Ghiadoni L., Gennari A., Fasolo C. B., Sudano I., Salvetti A. Aging and endothelial function in normotensive subjects and patients with essential hypertension. Circulation. 1995;91:1981-1987.

    • Vaitkevicius P. V., Fleg J. L. , Engel J. H., O’Connor F. C., Wright J. G., Lakatta L. E., Yin F. C., Lakatta E. G. Effects of age and aerobic capacity on arterial stiffness in healthy adults. Circulation. 1993;88:1456-1462.

    • Verdecchia P., Angeli F. Reversal of left ventricular hypertrophy: what have recent trials taught us? Am. J. Cardiovasc. Drugs. 2004;4:369-378.

    • Zheng F., Plati A. R., Potier M., Schulman Y., Berho M., Banerjee, Leclrecq B., Zisman A., Striker L. J., Striker G. E. Resistence to glomerulosclerosis in B6 mice dissapears after menopause. Am. J. Pathol. 2003;162:1339-1348.

       

    Capítulo 13. Envejecimiento músculo-esquelético

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    • Baron R. General principles of bone biology. En: Favus M. J. ed. Primer on the bone diseases and disorders of mineral metabolism. 5 ed. Washington. American Society for Bone and Mineral Research. 2003:1-8.

    • Bischoff-Ferrari H. A., Dawson-Hughes B., Willett W. C., Staehelin H. B., Bazemore M. G., Zee R. Y., Wong J. B. Effect of vitamin D on falls. A meta-analysis. JAMA 2004;291; 1999-2006.

    • Bischoff-Ferrari H. A., Willet W. C., Wong J. B., Giovanucci E., Dietrich T., Dawson-Hughes B. Fracture prevention with vitamin D supplementation. A meta-analysis of randomised controlled trials. JAMA 2005;293:2257-2264.

    • Canalis E. Mechanisms of glucocorticoid-induced osteoporosis. Curr. Opin. Rheumatol. 2003;15:454-7.

    • Chapuy M. C., Arlot M. E., Duboeuf F., Brun J., Crouzet B., Arnaud S., Delmas P. D., Meunier P. J. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N. Engl. J. Med. 1992;327:1637-1642.

    • Compston J. E. Vitamin D deficiency: time for action. BMJ 1998;317:1466-1467.

    • Dawson-Hughes B., Harris S. S., Krall E. A., Dallal G. E. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N. Engl. J. Med. 1997;337:670-676.

    • Dawson-Hughes B. The role of vitamin D in frature prevention. BoeKEy-Osteovision 2005;2:6-10 (a).

    • Dawson-Hughes B., Heaney R. P., Holick M. F., Lips P., Meunier P. J., Vieth R. Estimates of optimal vitamin D status. Osteoporos. Int. (Publicado online: 18 Marzo 2005) (b).

    • Delbonos O. Mollecular mechanism and therapeutic of the deficit on specific force in ageing skeletal muscle. Biogerontology 2002;3:265-270.

    • Deschenes M. R. Effects of aging on muscle fibre type and size. Sports Med. 2004;34: 809-824.

    • Dirks A. J., Leeuwenburgh C. The role of apoptosis in age related skeletal muscle atrophy. Sports Med. 2005;35:473-483.

    • Doherty T. J. The influence of aging and sex on skeletal muscle mass and strength. Curr. Opin. Clin. Nutr. Metab. Care 2001;4:503-508.

    • Erlich P. J., Lanyon L. E. Mechanical strain and bone cell function: a review. Osteoporos. Int. 2002;13:688-700.

    • González Macías J. Osteoporosis primaria: epidemiología y diagnóstico. En: Riancho J. A. y González Macías J. eds. Manual práctico de osteoporosis y enfermedades del metabolismo mineral. Madrid. Jarpyo Editores S. A. 2004;105-110.

    • González Macías J., Olmos J. M. Introducción: fisiopatología del remodelado óseo. En: Nogués X ed. Formadores de hueso. Barcelona, Scientific Communication Management 2005:13-25.

    • González Macías J., Hernández J. L., Olmos J. M. Risk factors for osteoporosis and osteoporotic fractures. Avd. Osteoporotic Fract. Manag. 2005;4:2-10.

    • Grothos S., Chen S., Wang C. Y., Robey P. G., Shi S. Telomerase accelerates osteogenesis of bone marrow stromal cells by upregulation of the Cbfa1, osterix, and osteocalcin. J. Bone Miner. Res. 2000:18:716-727.

    • Guillet C., Auguste P., Mayo W., Kreher P., Gascan H. Ciliary neurotrophic factor is a regulator of muscular stregth in aging. J. Neurosci. 1999;19:1257-1262.

    • Gutierrez G. Regulación paracrina del hueso. En: Riancho J. A., González Macías J. eds. Manual práctico de osteoporosis y enfermedades del metabolismo mineral. Madrid, Jarpyo Editores S. A.; 2004:13-18.

    • Halloran B. P., Ferguson V. L., Simske S. J., Burghardt A., Venon L. L., Majumdar S. Changes in bone structure and mass with advancing age in male C57BL/6J mice. J. Bone Miner. Res. 2002;17:1044-1050.

    • Hameed M., Harridge S. D., Goldspink G. Sarcopenia and hypertrophy: a role for insulin-growth factor I in aged muscle. Exerc. Sport Sci. Rev. 2002;30:15-19.

    • Heaney R. P. Calcium, parathyroid function, bone, and aging. J. Clin. Endocrinol. Metab. 1996;81:1697-1698.

    • Heikinheimo R. J., Inkovaara J. A., Harju E. J., Haavisto M. V., Kaarela R. H., Kataja J. M., et al. Annual injection of vitamin D and fractures of aged bones. Calcif. Tissue Int. 1992;51:105-10.

    • Hofbauer L. C., Henfelder A. E. The role of receptor activator of nuclear factor k-B ligand and osteoprotegerin in the pathogenesis and treatment of metabolic bone diseases. J. Clin. Invest. 2000;85:2355-2363.

    • Holick M. F., Matsuoka L. Y., Worstman J. Age, vitamin D, and solar ultraviolet radiation. Lancet 1989; 4:1104-1105.

    • Holick M. F., Siris E. S., Binkley N., Beard M. K., Khan A., Katzer J. T., Petruschke R. A., Chen E., de Papp A. E. Prevalence of vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J. Clin. Endocrinol. Metab.2005;90:3215-3224.

    • Langlois J. A., Rosen C. J., Visser M., et al. Association between insulin-like growth factor I and bone mineral density in older women and men: the Framingham cohort study. J. Clin. Endocrinol. Metab. 1998;83:4257-4262.

    • Lanyon L., Skerry T. Postmenopausal osteoporosis as a failure of bone’s adaptation to functional loading: a hypothesis. J. Bone Miner. Res. 2001;16:1937-1947.

    • Lips P., Graafmans W. C., Ooms M. E., Bezemer P. D., Bouter L. M. Vitamin D supplementation and fracture incidence in elderly persons: a randomised, placebo-controlled clinical trial. Ann. Intern. Med. 1996;124 400-406.

    • Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocrine Rev. 2001;22:477-501.

    • Manolagas S. C. Birth and death of bone cells: basic and regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocrine Rev. 2000; 21:115-137.

    • McKane W. R., Khosla S., Egan K. S., Robins S. P., Burritt M. F., Riggs B. L. Role of calcium intake in modulating age-related increases in parathyroid function and bone resorption. J. Clin. Endocrinol. Metab. 1996;81:1699-1703.

    • Mezquita P., Muñoz M. Alonso A. Otras hormonas: hormonas tiroideas, GH, glucocorticoides. En: Riancho J. A. y González Macías J. eds. Manual práctico de osteoporosis y enfermedades del metabolismo mineral. Madrid. Jarpyo Editores S. A. 2004;45-48.

    • Mosekilde L. Vitamin D and the elderly. Clin. Endocrinol. 2005;62:265-281.

    • Mundy G. R., Chen D., Oyajobi D. O. Bone remodelling. En: Favus M. J. ed. Primer on the bone diseases and disorders of mineral metabolism. 5 ed. Washington. American Society for Bone and Mineral Research. 2003:46-58.

    • Munuera L., Martínez M. E., Delgado A. Fisiopatología del hueso del anciano. En: Ferrández L. ed. Fracturas en el anciano. Madrid, EGRAF SA; 2001:23-34.

    • Olmos J. M. Martínez J., García J., Matorras P., Moreno J. J. González Macías J. Incidencia de fractura de cadera en Cantabria. Med. Clin. (Barc.) 1992;99:729-731.

    • Olmos J. M. Osteopatías metabólicas. En: Rodés J., Guardia J., eds. Medicina Interna. Barcelona, Masson SA; 2004:2704-2723. 

    • Ophoff J., Vanderschueren D. The senile osteoporosis mouse model SAMP-6: the ideal animal model for human osteoporosis? BoneKey–Osteovision, 2005;2:26-34.

    • Parfitt A. M. Osteomalacia and related disorders. En: Avioli L. V., Krane S. M., eds. Metabolic Bone Disease (2 ed.). San Diego. Academic Press; 1994:329-396.

    • Porthouse J., Cockayne S., King C., et al. Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care. BMJ 2005;330:1003-1010.

    • Quesada J. M. ed. 25-Hidroxivitamina D y osteoporosis. Barcelona. Trajecte SA 1998.

    • Quesada J. M. Vitamina D. En: Riancho J. A. y González Macías J. eds. Manual práctico de osteoporosis y enfermedades del metabolismo mineral. Madrid. Jarpyo Editores SA 2004;29-33.

    • Raisz L. W., Seeman E. Causes of age-related bone loss and bone fragility: an alterantive view. J. Bone Miner. Res. 2001;16:1948-1952.

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    • Riancho J. A., Zarrabeitia M. T., Amado J. A., Olmos J. M., González Macías J. Age-related differences in cytokine secretion. Gerontology 1994;40:8-12.

    • Riancho J. A. Hormonas sexuales. En: Riancho J. A. y González Macías J. eds. Manual práctico de osteoporosis y enfermedades del metabolismo mineral. Madrid. Jarpyo Editores S. A. 2004;42-44.

    • Rosen C. J., Kiel D. P. Age-related osteoporosis. En: Favus M. J. ed. Primer on the bone diseases and disorders of mineral metabolism. 5 ed. Washington. American Society for Bone and Mineral Research. 2003:89-92.

    • Rubenof R., Harris T. B., Abad L. W., et al. Monocyte cytokine production in elderly population: effect of age and inflammation. J. Gerontol. 1998;53:M20-M26.

    • Seeman E. Periosteal bone formation-a neglected determinant of bone strength. N. Engl. J. Med. 2003;349:320-3.

    • Trivedi D. P., Doll R., Khaw K. T. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ 2003;326:469-472.

    • Torrijos A. Calcio y vitamina D. En: Díaz Curiel M. ed. Actualización de osteoporosis. Madrid. FHOEMO. 2001;93-102.

    • Venning G. Recent developments in vitamin D deficiency and muscle weakness among elderly people. BMJ 2005;330:524-526.

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    Capítulo 14. Fundamentos biológicos del envejecimiento neurocognitivo

    • Baddeley A. Working memory: looking back and looking forward. Nat. Rev. Neurosci. 2003;4:829-839.

    • Brink J. M., McDowd J. M. Aging and selective attention: an issue of complexity or multiple mechanisms? J. Gerontol. B. Psychol. Sci. Soc. Sci. 1999;54:30-33.

    • Buchman A. S., Wilson R. S., Bienias J. L., Shah R. C., Evans D. A., Bennett D. A. Change in body mass index and risk of incident Alzheimer disease. Neurology. 2005;65:892-897.

    • Compton D. M., Bachman L. D., Logan J. A. Aging and intellectual ability in young, middle-aged, and older educated adults: preliminary results from a sample of college faculty. Psychol. Rep. 1997;81:79-90.

    • Darley C. F., Klatzky R. L., Atkinson R. C. Effects of memory load on reaction time. J. Exp. Psychol. 1972;96:232-234.

    • Dening T., Barapatre C. Mental health and the ageing population. J. Br. Menopause Soc. 2004;10:49-53.

    • Diehl M., Coyle N., Labouvie-Vief G. Age and sex differences in strategies of coping and defense across the life span. Psychol. Aging. 1996;11:127-139.

    • Doerksen S., Shimamura A. P. Source memory enhancement for emotional words. Emotion. 2001;1:5-11. 

    • Dustman R. E., Emmerson R. Y., Ruhling R. O., Shearer D. E., Steinhaus L. A., Johnson S. C., Bonekat H. W., Shigeoka J. W. Age and fitness effects on EEG, ERPs, visual sensitivity, and cognition. Neurobiol. Aging. 1990;11:193-200.

    • Dustman R. E., Shearer D. E., Emmerson R. Y. Life-span changes in EEG spectral amplitude, amplitude variability and mean frequency. Clin. Neurophysiol. 1999;110:1399-1409.

    • Emerit J., Edeas M., Bricaire F. Neurodegenerative diseases and oxidative stress. Biomed. Pharmacother. 2004;58:39-46.

    • Eusop E., Sebban C., Piette F. Aging and cognitive slowing: example of attentional processes—evaluation procedures and related questions. Encephale. 2001;27:39-44.

    • Folstein M. F., Folstein S. E., McHugh P. R. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 1975;12:189-198.

    • Johansson B. B. Brain plasticity in health and disease. Keio J. Med. 2004;53:231-246. 

    • Kausler D. H., Wiley J. G., Lieberwitz K. J. Adult age differences in short-term memory and subsequent long-term memory for actions. Psychol. Aging. 1992;7:309-316.

    • Kiraly M. A., Kiraly S. J. The effect of exercise on hippocampal integrity: review of recent research. Int. J. Psychiatry Med. 2005;35:75-89.

    • Kolb B., Whishaw I. Q. Brain plasticity and behaviour. Annu. Rev. Psychol. 1998;49:43-64.

    • Launer L. J. The epidemiologic study of dementia: a life-long quest? Neurobiol. Aging. 2005;26:335-340.

    • Lobo A., Saz P., Marcos G., Dia J. L., de la Camara C., Ventura T., Morales Asin F., Fernando Pascual L., Montanes J. A., Aznar S. Revalidation and standardization of the cognition mini-exam (first Spanish version of the Mini-Mental Status Examination) in the general geriatric population. Med. Clin. (Barc). 1999;112:767-774.

    • Morris J. C. Mild cognitive impairment and preclinical Alzheimer’s disease. Geriatrics. 2005;Suppl:9-14.

    • Mulatu M. S., Schooler C. Longitudinal effects of occupational, psychological, and social background characteristics on health of older workers. Ann. N. Y. Acad. Sci. 1999;896:406-408.

    • Myers C. E., Shohamy D., Gluck M. A., Grossman S., Kluger A., Ferris S., Golomb J., Schnirman G., Schwartz R. Dissociating hippocampal versus basal ganglia contributions to learning and transfer. J. Cogn. Neurosci. 2003;15:185-193.

    • Owens W. A. Age and mental abilities: a second adult follow-up. J. Educ. Psychol. 1966;57:311-325.

    • Pierucci-Lagha A., Derouesne C. Alcoholism and aging. 2. Alcoholic dementia or alcoholic cognitive impairment? Psychol. Neuropsychiatr. Vieil. 2003;1:237-249.

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    • Rubin D. C., Rahhal T. A., Poon L. W. Things learned in early adulthood are remembered best. Mem. Cognit. 1998;26:3-19.

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    Capítulo 15. Neurodegeneración y aportaciones terapéuticas

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    • Braak H., Braak R. Patterns of cortical lesions in Alzheimer’s disease. En: Alzheimer’s disease: biology, diagnosis and therapeutics. Iqbal K., Winblad B., Nishimura T., Takeda M., Wisniewski H. M. (editores). John Wiley & Sons Ltd. London 1997;227-237.

    • Busciglio J., Yankner B. A. Apoptosis and increased generation of reactive oxygen species in Down’s syndrome neurons in vitro. Nature 1995;378:776-779.

    • Busciglio J., Pelsman A., Wong C., Pigino G., Yuan M., Nori H., Yankner B. A. Altered metabolism of the amyloid ß precursor protein is associated with mitochondrial dysfunction in Down’s syndrome, Neuron 2002;33:677-688.

    • Capone G., Kim P., Jovanovich S., Payne L., Freund L., Welch K., Miller E., Trush M. Evidence for increased mitochondrial superoxide production in Down syndrome. Life Sci. 2002;70:2885-2895.

    • Cataldo A. M., Peterhoff C. M., Troncoso J. C., Gomez-Isla T., Hyman B. T., Nixon R. A. Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer’s disease and Down syndrome: differential effects of APOE genotype and presenilin mutations. Am. J. Pathol. 2000;157:277-286.

    • Cataldo A. M., Petanceska S., Peterhoff C. M., Terio N. B., Epstein C. J., Villar A., Carlson E. J., Staufenbiel M., Nixon R. A. App. gene dosage modulates endosomal abnormalities of Alzheimer’s disease in a segmental trisomy 16 mouse model of Down syndrome. J. Neurosci. 2003;23:6788-6792. 

    • Caughey B., Lansbury P. T. Protofibrils, pores, fibrils, and neurodegeneration: separating the responsable protein aggregates from the innocent bystanders. Annu. Rev. Neurosci. 2003;26:267-298.

    • Chicoine B., McGuire D. Longevity of a woman with Down syndrome: a case study. Ment. Retard 1997;35:477-479.

    • Engidawork E., Lubec G. Molecular changes in fetal Down syndrome brain. J Neurochemistry 2003;84:895-904.

    • Flórez J. Síndrome de Down y envejecimiento. En: www.down21.org/salud/salud/Envejecimiento_y_SD.htm. 2002.

    • Flórez J. Síndrome de Down: presente y futuro. Rev. Síndrome Down 2003a;20:16-22.

    • Flórez J. Farmacología de las demencias y de las conductas anormales. En: Farmacología Humana. Flórez J., Armijo J. A., Mediavilla A. (editores). Masson. Barcelona. 2003b; 623-634.

    • Flórez J., Ruiz E. Síndrome de Down. En: Síndromes específicos e individualidad de los apoyos: un enfoque interdisciplinar. Del Barrio J. A., Borragán A. (editores). Universidad de Cantabria, Departamento de Educación. Santander. 2003;41-57.

    • German D. C., Eisch A. J. Mouse models of Alzheimer’s disease: insiight into treatment. Rev. Neurosci. 2004;15:353-369.

    • Harris-Cerruti C., Kamsler A., Kaplan B., Lamb B., Segal M., Groner Y. Functional and morphological alterations in compound transgenic mice overexpressing Cu/Zn superoxide dismutase and amyloid precursor protein. Eur. J. Neurosci. 2004;19:1174-1190.

    • Kim S. H., Vikolinsky R., Cairns N., Lubec G. Decreased levels of complex III core protein 1 and complex V beta chain in brain from patients with Alzheimers’s disease and Down syndrome. Cell. Mol. Life Sci. 2000;57:1810-1816.

    • Klein W. L., Krafft G. A., Finch C. E.  Targetting small Aß oligomers; the solution to an Alzheimer’s disease conundrum? Trends Neurosci. 2001;24:219-224.

    • Lemere C. A., Blusztajn J. K., Yamaguchi H., Visniewski T., Saido T. C., Selkow D. J. Sequence of deposition of heterogeneous amyloid beta-peptides and APO E in Down syndrome: implications for initial events in amyloid plaque formation. Neurobiol. Dis.1996;3:16-32.

    • Lott I. T., Head E. Alzheimer disease and Down syndrome: factors in pathogenesis. Neurobiol. Aging 2005;26:383-389.

    • Lue L. F. Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimers’s disease. Am. J. Pathol. 1999;155:853-862.

    • Mazur-Kolecka B., Kowal D., Sukontasup T., Dickson D., Frackowiak J. The effect of oxidative stress on accumulation of apolipoprotein E3 and E4 in a cell culture model of ß-amyloid angiopathy (CAA). Brain Res. 2003;983:48-57.

    • McNamara M. J., Gomez-Isla T., Hyman B. T. Apolipoprotein E genotype and deposits of Abeta40 and Abeta42 in Alzheimer disease. Arch. Neurol. 1998;55:1001-1004.

    • Mehta P. D., Dalton A. J., Mehta S. P., Kim K. S., Sersen E. A., Wisniewski H. M. Increased plasma amyloid beta protein 1-42 levels on Down syndrome. Neurosci. Let. 1998;241:13-16.

    • Mori C., Spooner E. T., Wisniewski K. E., Wisniewski T. M., Yamaguchi H., Saido T. C., Tolan D. R., Selkoe D. J., Lemere C. A. Intraneuronal Aß42 accumulation in Down syndrome brain. Amyloid: J. Protein Folding Disord. 2002;9:88-102.

    • Pascual J. Enfermedades degenerativas del sistema nervioso. En: Medicina Interna. Rodés J., Guardia J. (editores). Masson. Barcelona. 2004;1998-2017.

    • Pelsman A., Hoyo-Vadillo C., Gudasheva T. A., Seredenin S. B., Ostrovskaya RU, Busciglio J. GVS-111 prevents oxidative damage and apoptosis in normal and Down’s syndrome human cortical neurons. Int. J. Devl. Neuroscience. 2003;21:117-124.

    • Polvikoski T., Sulkava R., Haltia M., Kainulainen K., Vuorio A., et al. Apolipoprotein E., dementia and cortical deposition of beta-amyloid protein. N. Eng. J. Med. 1995;333: 1242-1247.

    • Prasher V. P., Huxley A., Haque M. S. and the Down syndrome Ageing Study Group. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Down syndrome and Alzheimer’s disease – Pilot Study. Int. J. Geriat. Psychiatry 2002;17: 270-278.

    • Rang H. P., Dale M. M., Ritter J. M., Moore P. K. Farmacología, 5ª edic. Elsevier España. Barcelona. 2004;495.

    • Schupf N., Kapell D., Lee J. H., Zigman W., Canto B., Tycko B., Mayeux R. Onset of dementia is associated with apolipoprotein E epsilon 4 in Down’s syndrome. Ann. Neurol. 1996;40:799-801.

    • Schupf N., Patel B., Silverman W., Zigman W. B., Zhong N., Tycko B., Mehta P. D., Mayeux R. Elevated plasma amyloid ß-peptide 1-42 and onset of dementia on adults with Down syndrome. Neurosci. Let. 2001;301:199-203.

    • Selkoe D., Kopan R. Notch and presenilins: regulated intramembrane proteolysis links development and degeneration. Annu. Rev. Neurosci. 2003;26:565-597.

    • Teller J. K., Russo C., DeBusk L. M., Angelini G., Zaccheo D., Dagna-Bricarelli F., Scartezzini P., Bertolini S., Mann D. M., Yabaton M., Gambetti P.  Presence of soluble amyloid beta peptide precedes amyloid plaque formation in Down’s syndrome. Nat. Med.1996;2:93-95.

    • Tokuda Y., Fukushima T., Ikeda S-I., Sekijima Y., Shoji S., Yanagisawa N., Tamaoka A. Plasma levels of amyloid ß protein Aß 1-40 and Aß 1-42(43) are elevated in Down’s syndrome. Ann. Neurol. 1997;41:271-273.