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Inicio Revista Española de Geriatría y Gerontología Envejecimiento y resistencia a la insulina. Más allá del síndrome metabólico
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Vol. 42. Núm. 5.
Páginas 302-311 (Septiembre 2007)
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Vol. 42. Núm. 5.
Páginas 302-311 (Septiembre 2007)
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Envejecimiento y resistencia a la insulina. Más allá del síndrome metabólico
Ageing and insulin resistance. Beyond the metabolic syndrome
Carles Zafon Llopis
Autor para correspondencia

Correspondencia: Dr. C. Zafon. Llibertat, 65 A. 08150 Parets del Vallès. Barcelona. España.
División de Endocrinología. Hospital General i Universitari Vall d’Hebron. Barcelona. España
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La disminución de la sensibilidad al efecto de la insulina de diversos tejidos es conocida como resistencia insulínica. El envejecimiento es una etapa de la vida que se acompaña de profundos cambios metabólicos, entre ellos la reducción en la tolerancia a los hidratos de carbono. Sin negar la progresiva pérdida de la capacidad pancreática para producir insulina, numerosos estudios han podido demostrar que la intolerancia a los glúcidos se debe, fundamentalmente, a la resistencia insulínica. Así, el fenómeno que se ha implicado como elemento causal en el epidémico síndrome metabólico, que abarca tanto la obesidad como la diabetes mellitus, aparece como un hecho natural en la senescencia. En este trabajo se revisa la relación que hay entre resistencia a la insulina y envejecimiento. Asimismo, se exponen las posibles causas que determinan esa relación y, finalmente, se analiza su supuesta razón evolutiva, para justificar cómo una circunstancia aparentemente tan nociva puede formar parte del proceso fisiológico de envejecer.

Palabras clave:
Resistencia insulínica
Tejido adiposo
Estrés oxidativo

Insulin resistance is defined as the decreased ability of tissues to respond to physiological insulin levels. Ageing is a stage of life accompanied by profound metabolic changes, among which is reduced carbohydrate tolerance. Although age-related insulin secretory dysfunction may play a role in this phenomenon, numerous studies have demonstrated that age-dependent carbohydrate intolerance can be mainly attributed to insulin resistance.

Thus, the phenomenon that has been implicated as a causal element in the epidemic of metabolic syndrome, which includes both obesity and diabetes mellitus, appears as a natural occurrence in ageing. The present article reviews the relationship between insulin resistance and ageing. Moreover, the possible causes of this association are discussed. Finally, the evolutionary purposes of this association are analyzed to explain how a circumstance seemingly so harmful is included in the physiological process of senescence.

Key words:
Insulin resistance
Adipose tissue
Oxidative stress
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H. Himsworth.
Diabetes mellitus: its differentiation into insulin-sensitive and insulin-insensitive types.
Lancet, 1 (1936), pp. 127-130
R. Yalow, S. Berson.
Immunoassay of endogenous plasma insulin in man.
J Clin Invest, 39 (1960), pp. 1157-1175
H. Lebovitz.
Insulin resistance: definition and consequences.
Exp Clin Endocrinol Diabetes, 109 (2001), pp. S135-S148
G.M. Reaven.
Role of insulin resistance in human disease.
Diabetes, 37 (1988), pp. 1595-1607
B. Leslie.
Metabolic syndrome: historical perspective.
Am J Med Sci, 330 (2005), pp. 264-268
K.G.M.M. Alberti, P.Z. Zimmet, J. Shaw.
Metabolic syndrome — a new worldwide definition. A consensus statement from the International Diabetes Federation.
Diabet Med, 23 (2006), pp. 469-480
M. Koffler, L. Ramirez, P. Raskin.
Insulin resistance and diabetes, mechanism and possible intervention.
Diabetes Res Clin Pract, 7 (1989), pp. 83-98
T. Wallace, D. Matthews.
The assessment of insulin resistance in man.
Diabet Med, 19 (2002), pp. 527-534
G.M. Reaven.
Why syndrome X? From Harold Himsworth to the insulin resistance syndrome.
Cell Metab, 1 (2005), pp. 9-14
M. Wendorf, I. Goldfine.
Excavation of the “thrifty” genotype.
Diabetes, 40 (1991), pp. 161-165
J. Brand Miller, S. Colagiuri.
The carnivore connection: dietary carbohydrate in the evolution of NIDDM.
Diabetologia, 37 (1994), pp. 1280-1286
J. Fernández-Real, W. Ricart.
Insulin resistance and inflammation in an evolutionary perspective: the contribution of cytokine genotype/phenotype to thriftiness.
Diabetologia, 42 (1999), pp. 1367-1374
E. Shafrir.
Development and consequences of insulin resistance: lessons from animals with hyperinsulinaemia.
Diabetes Metab, 22 (1996), pp. 122-131
J.V. Neel.
Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”?.
Am J Hum Genet, 14 (1962), pp. 353-362
D. Elahi, D. Muller.
Carbohydrate metabolism in the elderly.
Eur J Clin Nutr, 54 (2000), pp. S112-S120
A. Chang, J. Halter.
Aging and insulin secretion.
Am J Physiol Endocrinol Metab, 284 (2003), pp. E7-E12
J. Radziuk.
Insulin sensitivity and its measurement: structural commonalities among the methods.
J Clin Endocrinol Metab, 85 (2000), pp. 4426-4433
F. Silverstone, M. Brandfonbrener, N. Shock, M. Yiengst.
Age differences in the intravenous glucose tolerance tests an the response to insulin.
J Clin Invest, 36 (1957), pp. 504-514
C. Heard, W. Soerjodibroto, S. Frangi, A. Exton-Smith.
Glucose tolerance, plasma insulin levels and insulin sensitivity in geriatric patients.
Proc Nutr Soc, 34 (1975), pp. A86-A87
W. Soerjodibroto, C. Heard, A. Exton-Smith.
Glucose tolerance, plasma insulin levels and insulin sensitivity in elderly patients.
Age Ageing, 8 (1979), pp. 65-74
E. Pisu, A. Diana, A. Lombardi, M. Cassader, G. Pagano.
Diurnal variations in insulin secretion and insulin sensitivity in aged subjects.
Acta Diabetol Lat, 17 (1980), pp. 153-160
J. Rowe, K. Minaker, J. Pallotta.
Characterization of the insulin resistance of aging.
J Clin Invest, 71 (1983), pp. 1581-1587
R. Fink, O. Kolterman, J. Griffin, J. Olefsky.
Mechanisms of insulin resistance in aging.
J Clin Invest, 71 (1983), pp. 1523-1535
M. Chen, R. Bergman, G. Pacini, D. Porte.
Pathogenesis of age-related glucose intolerance in man: insulin resistance and decreased beta-cell function.
J Clin Endocrinol Metab, 60 (1985), pp. 13-20
D. Elahi, D. Muller, M. McAloon-Dyke, J. Tobin, R. Andres.
The effect of age on insulin response and glucose utilization during four hyperglycemic plateaus.
Exp Gerontol, 28 (1993), pp. 393-409
E. Ferrannini, S. Vichi, H. Beck-Nielsen, M. Laakso, G. Paolisso, U. Smith.
Insulin action and age. European Group for the Study of Insulin Resistance (EGIR).
Diabetes, 45 (1996), pp. 947-953
R. Basu, E. Breda, A. Oberg, C. Powell, Ch. Dalla Man, A. Basu, et al.
Mechanisms of the age-associated deterioration in glucose tolerance. Contribution of alterations in insulin secretion, action, and clearance.
Diabetes, 52 (2003), pp. 1738-1748
S. Chevalier, R. Gougeon, N. Choong, M. Lamarche, J. Morais.
Influence of adiposity in the blunted whole-body protein anabolic response to insulin with aging.
J Gerontol A Biol Sci Med Sci, 61A (2006), pp. 156-164
B.B. Kahn, J.S. Flier.
Obesity and insulin resistance.
J Clin Invest, 106 (2000), pp. 473-481
B. Rasmussen, A. Fujita, R.R. Wolfe, B. Mittendorfer, M. Roy, V.L. Rowe, et al.
Insulin resistance of muscle protein metabolism in aging.
FASEB J, 20 (2006), pp. 768-769
G. Kimmerling, W. Javorski, G.M. Reaven.
Aging and insulin resistance in a group of nonobese male volunteers.
J Am Geriatr Soc, 25 (1977), pp. 349-353
G. Pacini, A. Valerio, F. Beccaro, R. Nosadini, C. Cobelli, G. Crepaldi.
Insulin sensitivity and beta-cell responsivity are not decreased in elderly subjects with normal OGTT.
J Am Geriatr Soc, 36 (1988), pp. 317-323
R. Bourey, W. Kohrt, J. Kirwan, M. Staten, D. King, J. Holloszy.
Relationship between glucose tolerance and glucose-stimulated insulin response in 65- years-olds.
J Gerontol, 48 (1993), pp. M122-M127
G. Boden, X. Chen, R. DeSantis, Z. Kendrick.
Effects of age and body fat on insulin resistance in healthy men.
Diabetes Care, 16 (1993), pp. 728-733
H. Shimokata, D. Muller, J. Fleg, J. Sorkin, A. Ziemba, R. Andres.
Age as independent determinant of glucose tolerance.
Diabetes, 40 (1991), pp. 144-151
G. Paolisso, M. Tagliamonte, M. Rizzo, D. Giugliano.
Advancing age and insulin resistance: new facts about an ancient history.
Eur J Clin Invest, 29 (1990), pp. 758-769
E. Perissinotto, C. Pisent, G. Sergi, F. Grigoletto, G. Enzi.
Anthopometric measurements in the elderly: age and gender differences.
Br J Nutr, 87 (2002), pp. 177-186
S.B. Roberts, G.E. Dallal.
Effects of age on energy balance.
Am J Clin Nutr, 68 (1998), pp. S975-S979
S.S. Guo, C. Zeller, W.C. Chumlea, R.M. Siervogel.
Aging, body composition, and lifestyle: the Fels longitudinal study.
Am J Clin Nutr, 70 (1999), pp. 405-411
V.A. Hughes, W.R. Frontera, R. Roubenoff, W.J. Evans, M.A. Fiatarone Singh.
Longitudinal changes in body composition in older men and women: role of body weight change and physical activity.
Am J Clin Nutr, 76 (2002), pp. 473-481
L.S. Piers, M.J. Soares, L.M. McCormack, K. O’Dea.
Is there evidence for an agerelated reduction in metabolic rate?.
J Appl Physiol, 85 (1998), pp. 2196-2204
B. Beaufrère, B. Morio.
Fat and protein redistribution with aging: metabolic considerations.
Eur J Clin Nutr, 54 (2000), pp. S48-S53
W.F. DeNino, A.T. Tchernof, I.J. Dionne, M.J. Toth, P.A. Ades, C.K. Sites, et al.
Contribution of abdominal adiposity to age-related differences in insulin sensitivity and plasma lipids in healthy nonobese women.
Diabetes Care, 24 (2001), pp. 925-932
J. Seidell, T. Visscher.
Body weight and weight change and their health implications for the elderly.
Eur J Clin Nutr, 54 (2000), pp. S33-S39
W. Kohrt, J. Kirwan, M. Staten, R. Bourey, D. King, J. Holloszy.
Insulin resistance in aging is related to abdominal obesity.
Diabetes, 42 (1993), pp. 273-281
P. Coon, E. Rogus, D. Drinkwater, D. Muller, A. Goldberg.
Role of body fat distribution in the decline in insulin sensitivity and glucose tolerance with age.
J Clin Endocrinol Metab, 75 (1992), pp. 1125-1132
P. Imbeault, J.B. Prins, M. Stolic, A.W. Russell, T. O’Moore-Sullivan, J.P. Després, et al.
Aging per se does not influence glucose homeostasis.
Diabetes Care, 26 (2003), pp. 480-484
B. Bryni, T. Jenssen, K. Olafsen, J. Eikrem.
Age or waist as determinant of insulin action?.
Metabolism, 52 (2003), pp. 850-857
N. Barzilai, G. Gupta.
Interaction between aging and syndrome X: new insights on the pathophysiology of fat distribution.
Ann NY Acad Sci, 892 (1999), pp. 58-72
I. Gabriely, X. Hui Ma, X. Man Yang, G. Atzmon, M.W. Rajala, A.H. Berg, et al.
Removal of visceral fat prevents insulin resistance and glucose intolerance of aging. An adipokine-mediated process?.
Diabetes, 51 (2002), pp. 2951-2958
K. Esposito, G. Giugliano, N. Scuderi, D. Giugliano.
Role of adipokines in the obesity-inflammation relationship: the effect of fat removal.
Plast Reconstr Surg, 118 (2006), pp. 1048-1057
F. Giorgino, L. Laviola, J. Eriksson.
Regional differences of insulin action in adipose tissue: insights from in vivo and in vitro studies.
Acta Physiol Scand, 183 (2005), pp. 13-30
L. Laviola, S. Perrini, A. Cignarelli, A. Natalicchio, A. Leonardini, F. De Stefano, et al.
Insulin signaling in human visceral and subcutaneous adipose tissue in vivo.
Diabetes, 55 (2006), pp. 952-961
M.D. Jensen.
Health consequences of fat distribution.
Horm Res, 48 (1997), pp. 88-92
S. Yamashita, T. Nakamura, I. Shimomura, M. Nishida, S. Yoshida, K. Kotani, et al.
Insulin resistance and body fat distribution.
Diabetes Care, 19 (1996), pp. 287-291
G. Boden.
Role of fatty acids in the pathogenesis of insulin resistance and NIDDM.
Diabetes, 46 (1997), pp. 3-10
D. Kelley, K. Williams, J. Price, T. McKolanis, B. Goodpaster, F. Thaete.
Plasma fatty acids, adiposity, and variance of skeletal muscle insulin resistance in type 2 diabetes mellitus.
J Clin Endocrinol Metab, 86 (2001), pp. 5412-5419
P. Kovacs, M. Stumvoll.
Fatty acids and insulin resistance in muscle and liver.
Best Pract Res Clin Endocrinol Metab, 19 (2005), pp. 625-635
A. Carpentier, S. Mittelman, B. Lamarche, R. Bergman, A. Giacca, G. Lewis.
Acute enhancement of insulin secretion by FFA in humans is lost with prolonged FFA elevation.
Am J Physiol, 276 (1999), pp. E1055-E1066
S. Hirabara, L. Silveira, F. Abdulkader, C. Carvalho, J. Procopio, R. Curi.
Timedependent effects of fatty acids on skeletal muscle metabolism.
J Cell Physiol, 210 (2007), pp. 7-15
G. Boden.
Interaction between free fatty acids and glucose metabolism.
Curr Opin Clin Nutr Metab Care, 5 (2002), pp. 545-549
K.F. Petersen, G.I. Shulman.
Etiology of insulin resistance.
Am J Med, 119 (2006), pp. S10-S16
G. Boden, B. Lebed, M. Schatz, C. Homko, S. Lemieux.
Effects of acute changes of plasma free fatty acids on intramyocellular fat content and insulin resistance in healthy subjects.
Diabetes, 50 (2001), pp. 1612-1617
G. Boden.
Fatty acid-induced inflammation and insulin resistance in skeletal muscle and liver.
Curr Diab Rep, 6 (2006), pp. 177-181
P. Arner.
Insulin resistance in type 2 diabetes: role of fatty acids.
Diabetes Metab Res Rev, 18 (2002), pp. S5-S9
G. Boden, P. Cheung, T. Stein, K. Kresge, M. Mozzoli.
FFA cause hepatic insulin resistance by inhibiting insulin suppression of glycogenolysis.
Am J Physiol Endocrinol Metab, 283 (2002), pp. E12-E19
M. Kabir, K. Catalano, S. Ananthnarayan, S.P. Kim, G.W. Van Citters, M.K. Dea, et al.
Molecular evidence supporting the portal theory: a causative link between visceral adiposity and hepatic insulin resistance.
Am J Physiol Endocrinol Metab, 288 (2005), pp. E454-E461
T. Lam, A. Carpentier, G. Lewis, G. Van der Werve, I. Fantus, A. Giacca.
Mechanisms of the free fatty acid-induced increase in hepatic glucose production.
Am J Physiol Endocrinol Metab, 284 (2003), pp. E863-E873
M.D. Jensen.
Is visceral fat involved in the pathogenesis of the metabolic syndrome?.
Obesity, 14 (2006), pp. S20-S24
Y. Zhang, R. Proenca, M. Maffei, M. Barone, L. Leopold, J.M. Friedman.
Positional cloning of the mouse obese gene and its human homologue.
Nature, 372 (1994), pp. 425-432
J.S. Flier.
What’s in a name? in search of leptin’s physiologic role.
J Clin Endocrinol Metab, 83 (1998), pp. 1407-1413
J.M. Friedman, J.L. Halaas.
Leptin and the regulation of body weight in mammals.
Nature, 395 (1998), pp. 763-770
G.A. Bray, D.A. York.
Leptin and clinical medicine: a new piece in the puzzle of obesity.
J Clin Endocrinol Metab, 82 (1997), pp. 2771-2776
D. Porte, R.J. Seeley, S.C. Woods, D.G. Baskin, D. Figlewicz, M.W. Schwartz.
Obesity, diabetes and the central nervous system.
Diabetologia, 41 (1998), pp. 863-881
J.F. Caro, J. Kolaczynski, M.R. Nyce, J.P. Ohannesian, I. Opentanova, W.H. Goldman, et al.
Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance.
Lancet, 348 (1996), pp. 159-161
F. Lönnqvist, L. Nordfors, M. Schalling.
Leptin and its potential role in human obesity.
J Intern Med, 245 (1999), pp. 643-652
R. Carraro, A. Ruiz-Torres.
Mecanismos que aceleran el envejecimiento: relación de la resistencia a la leptina con la insulínica.
Rev Esp Geriatr Gerontol, 40 (2005), pp. 178-183
D.R. Mann, O.K. Johnson, T. Gimpel, V.D. Castracane.
Changes in circulating leptin, leptin receptor, and gonadal hormones from infancy until advanced age in humans.
J Clin Endocrinol Metab, 88 (2003), pp. 3339-3345
R. Carraro, A. Ruiz-Torres.
Relationship of serum leptin concentration with age, gender, and biomedical parameters in healthy, non-obese subjects.
Arch Gerontol Geriatr, 43 (2006), pp. 301-312
B. Baranowska, E. Wolinska-Witort, A. Baranowska-Bik, L. Martynska, M. Chmielowska.
Evaluation of neuroendocrine status in longevity.
Neurobiol Aging, 28 (2007), pp. 774-783
B. Wajchenberg, D. Giannella-Neto, M. Da Silva, R. Santos.
Depot-specific hormonal characteristics of subcutaneous and visceral adipose tissue and their relation to the metabolic syndrome.
Horm Metab Res, 34 (2002), pp. 616-621
K. Uysal, S. Wiesbrock, M. Marino, G. Hotamisligil.
Protection form obesity-induced insulin resistance in mice lacking TNF-a function.
Nature, 389 (1997), pp. 610-614
G. Hotamisligil.
The role of TNFa and TNF receptors in obesity and insulin resistance.
J Intern Med, 245 (1999), pp. 621-625
J. Fernández-Real.
Genetic predisposition to low-grade inflamation and type 2 diabetes.
Diabetes Technol Ther, 8 (2006), pp. 55-66
L. Rink, I. Cakman, H. Kirchner.
Altered cytokine production in the elderly.
Mech Ageing Dev, 102 (1998), pp. 199-209
H. Bruunsgaard.
Effects of tumor necrosis factor-alpha and interleukin-6 in elderly populations.
Eur Cytokine Netw, 13 (2002), pp. 389-391
J. Fernández-Real, W. Ricart.
El aumento de la actividad proinflamatoria es consustancial a la resistencia a la insulina.
Med Clin (Barc), 115 (2000), pp. 185-189
G. Paolisso, M.R. Rizzo, G. Mazziotti, M.R. Tagliamonte, A. Gambardella, M. Rotondi, et al.
Advancing age and insulin resistance: role of plasma tumor necrosis factor-alpha.
Am J Physiol, 275 (1998), pp. E294-E299
J. Ruige, D. Ballaux, T. Funahashi, I. Mertens, Y. Matsuzawa, L. Van Gaal.
Resting metabolic rate is an important predictor of serum adiponectin concentrations: potential implications for obesity-related disorders.
Am J Clin Nutr, 82 (2005), pp. 21-25
K. Saito, S. Arata, T. Hosono, Y. Sano, K. Takahashi, N.H. Choi-Miura, et al.
Adiponectin plays an important role in efficient energy usage under energy shortage.
Biochim Biophys Acta, 1761 (2006), pp. 709-716
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
S. Furler, S. Gan, A. Poynten, D. Chisholm, L. Campbell, A. Kriketos.
Relationship of adiponectin with insulin sensitivity in humans, independent of lipid availability.
Obesity, 14 (2006), pp. 228-234
Y. Okamoto, S. Kihara, T. Funahashi, Y. Matsuzawa, P. Libby.
Adiponectin: a key adipocytokine in metabolic syndrome.
Clin Sci, 110 (2006), pp. 267-278
H. Staiger, O. Tschritter, J. Machann, C. Thamer, A. Fritsche, E. Maerker, et al.
Relationship of serum adiponectin and leptin concentrations with body fat distribution in humans.
Obes Res, 11 (2003), pp. 368-372
H. Motoshima, X. Wu, M.K. Sinha, V.E. Hardy, E.L. Rosato, D.J. Barbot, et al.
Differential regulation of adiponectin secretion from cultured human omental and subcutaneous adipocytes: effects of insulin and rosiglitazone.
J Clin Endocrinol Metab, 87 (2002), pp. 5662-5667
T. Isobe, S. Saitoh, S. Takagi, H. Takeuchi, Y. Chiba, N. Katoh, et al.
Influence of gender, age and renal function on plasma adiponectin level: the Tanno and Sobetsu study.
Eur J Endocrinol, 153 (2005), pp. 91-98
E. Miles, D. Rees, T. Banerjee, R. Cazzola, S. Lewis, R. Wood, et al.
Age-related increases in circulating inflammatory markers in men are independent of BMI, blood pressure and blood lipid concentrations.
Atherosclerosis, (2006),
E. Zoico, V. Di Francesco, G. Mazzali, R. Vettor, F. Fantin, L. Bissoli, et al.
Adipocytokines, fat distribution, and insulin resistance in elderly men and women.
J Gerontol A Biol Sci Med Sci, 59 (2004), pp. M935-M939
W.J. Evans.
What is sarcopenia?.
J Gerontol A Biol Sci Med Sci, 50 (1995), pp. 5-8
S. Fujita, E. Volpi.
Amino acids and muscle loss with aging.
J Nutr, 136 (2006), pp. S277-S280
E. Volpi, R. Nazemi, S. Fujita.
Muscle tissue changes with aging.
Curr Opin Clin Nutr Metab Care, 7 (2004), pp. 405-410
D. Attaix, L. Mosoni, D. Dardevet, L. Combaret, P. Mirand, J. Grizard.
Altered responses in skeletal muscle protein turnover during aging in anabolic and catabolic periods.
Int J Bichem Cell Biol, 37 (2005), pp. 1962-1973
H. Karakelides, N. Sreekumaran.
Sarcopenia of aging and its metabolic impact.
Curr Top Dev Biol, 68 (2005), pp. 123-148
T. Vanitallie.
Frailty in the elderly: contributions of sarcopenia and visceral protein depletion.
Metabolism, 52 (2003), pp. 22-26
F. Dela, M. Kjaer.
Resistance training, insulin sensitivity and muscle function in the elderly.
Essays Biochem, 42 (2006), pp. 75-88
C. Ferrara, A. Goldberg, H. Ortmeyer, A. Ryan.
Effects of aerobic and resistive exercise training on glucose disposal and skeletal muscle metabolism in older men.
J Gerontol A Biol Sci Med Sci, 61 (2006), pp. 480-487
N. Hays, R. Starling, D. Sullivan, J. Fluckey, R. Coker, W.J. Evans.
Comparison of insulin sensitivity assessment indices with euglycemic-hyperinsulinemic clamp data after a dietary and exercise intervention in older adults.
Metabolism, 55 (2006), pp. 525-532
V. O’Leary, C. Marchetti, R. Krishnan, B. Stetzer, F. Gonzalez, J. Kirwan.
Exercise-induced reversal of insulin resistance in obese elderly is associated with reduced visceral fat.
J Appl Physiol, 100 (2006), pp. 1584-1589
K. Stewart, A. Bacher, K. Turner, J.G. Lim, P.S. Hees, E.P. Shapiro, et al.
Exercise and risk factors associated with metabolic syndrome in older adults.
Am J Prev Med, 28 (2005), pp. 9-18
S.W.J. Lamberts, A.W. Van den Beld, A.-J. Van der Lely.
The endocrinology of aging.
Science, 278 (1997), pp. 419-424
B. Lunenfeld.
Endocrinology of the aging male.
Minerva Ginecol, 58 (2006), pp. 153-170
A. Genazzani, M. Gambacciani.
Effect of climacteric transition and hormone replacement therapy on body weight and body fat distribution.
Gynecol Endocrinol, 22 (2006), pp. 145-150
F. Kohn.
Testosterone and body functions.
Aging Male, 9 (2006), pp. 183-188
D. Broughton, O. James, K. Alberti, R. Taylor.
Peripheral and hepatic insulin sensitivity in healthy elderly human subjects.
Eur J Clin Invest, 21 (1991), pp. 13-21
G. Pagano, S. Marena, L. Scaglione, P. Bodoni, G. Montegrosso, A. Bruno, et al.
Insulin resistance shows selective metabolic and hormonal targets in the elderly.
Eur J Clin Invest, 26 (1996), pp. 650-656
K.J.A. Davies.
Oxidative stress: the paradox of aerobic life.
Biochem Soc Symp, 61 (1995), pp. 1-31
K.B. Beckman, B.N. Ames.
The free radical theory of aging matures.
Physiol Rev, 78 (1998), pp. 547-581
T. Finkel, N. Holbrook.
Oxidants, oxidative stress and the biology of aging.
Nature, 408 (2000), pp. 239-247
T.R. Golden, S. Melov.
Mitochondrial DNA mutations, oxidative stress, and aging.
Mech Ageing Dev, 122 (2001), pp. 1577-1589
M.L. Hamilton, H. Van Remmen, J.A. Drake, H. Yang, Z. Mao Gou, K. Kewitt, et al.
Does oxidative damage to DNA increase with age?.
Proc Natl Acad Sci USA, 98 (2001), pp. 10469-10474
G. Barja.
Relación entre el estrés oxidativo mitocondrial y la velocidad del envejecimiento.
Rev Esp Geriatr Gerontol, 40 (2005), pp. 243-249
J. Miquel.
Integración de teorías del envejecimiento (parte I).
Rev Esp Geriatr Gerontol, 41 (2006), pp. 55-63
P. Ritz, G. Berrut.
Mitochondrial function, energy expenditure, aging and insulin resistance.
Diabetes Metab, 31 (2005),
A. Wiederkehr, C. Wollheim.
Minireview: implication of mitochondria in insulin secretion and action.
Endocrinology, 147 (2006), pp. 2643-2649
K.F. Petersen, D. Befroy, S. Dufour, J. Dziura, C. Ariyan, D.L. Rothman, et al.
Mitochondrial dysfunction in the elderly: possible role in insulin resistance.
Science, 300 (2003), pp. 1140-1142
K.R. Short, M.L. Bigelow, J. Kahl, R. Singh, J. Coenen-Schimke, S. Raghavakaimal, et al.
Decline in skeletal muscle mitochondrial function with aging in humans.
Proc Natl Acad Sci USA, 102 (2005), pp. 5618-5623
C.S. Stump, K.R. Short, M.L. Bigelow, J.M. Schimke, K.S. Nair.
Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts.
Proc Natl Acad Sci USA, 100 (2003), pp. 7996-8001
A. Ceriello, E. Motz.
Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited.
Arterioscler Thromb Vasc Biol, 24 (2004), pp. 816-823
N. Houstis, E. Rosen, E. Lander.
Reactive oxygen species have a causal role in multiple forms of insulin resistance.
Nature, 440 (2006), pp. 944-948
H. Urakawa, A. Katsuki, Y. Sumida, E.C. Gabazza, S. Murashima, K. Morioka, et al.
Oxidative stress is associated with adiposity and insulin resistance in men.
J Clin Endocrinol Metab, 88 (2003), pp. 4673-4676
B. Goldstein, K. Mahadev, X. Wu.
Insulin action is facilitated by insulin-stimulated reactive oxygen species with multiple potential signaling targets.
Diabetes, 54 (2005), pp. 311-321
G. Paolisso, M. Barbieri, M. Bonafè, C. Franceschi.
Metabolic age modelling: the lesson from centenarians.
Eur J Clin Invest, 30 (2000), pp. 888-894
P.D. Gluckman, M. Hanson.
The developmental origins of the metabolic syndrome.
Trends Endocrinol Metab, 15 (2004), pp. 183-187
S.B. Roberts, I. Rosenberg.
Nutrition and aging: changes in the regulation of energy metabolism with aging.
Physiol Rev, 86 (2006), pp. 651-667
E.J. Harper.
Changing perspectives on aging and energy requirements: aging and energy intakes in humans, dogs and cats.
J Nutr, 128 (1998), pp. S2623-S2626
J.E. Morley.
Decreased food intake with aging.
J Gerontol A Biol Sci Med Sci, 56A (2001), pp. 81-88
S. Biddinger, C. Kahn.
From mice to men: insights into the insulin resistance syndromes.
Annu Rev Physiol, 68 (2006), pp. 123-158
N. Klöting, M. Blüher.
Extended longevity and insulin signaling in adipose tissue.
Exp Gerontol, 40 (2005), pp. 878-883
F. Picard, L. Guarente.
Molecular links between aging and adipose tissue.
Int J Obes (Lond), 29 (2005), pp. S36-S39
N. Barzilai, G. Gupta.
Revisiting the role of fat mass in the life extension induced by caloric restriction.
J Gerontol A Biol Sci Med Sci, 54A (1999), pp. B89-B96
L. Barbour, J. Shao, L. Qiao, W. Leitner, M. Anderson, J.E. Friedman, et al.
Human placental growth hormone increases expression of the p85 regulatory unit of phosphatidylinositol 3-kinase and triggers severe insulin resistance in skeletal muscle.
Endocrinology, 145 (2004), pp. 1144-1150
B. Bryni, T. Jenssen, K. Olafsen, A. Bendikssen.
Oxidative and nonoxidative glucose disposal in elderly vs younger men with similar and smaller body mass indices and waist circumferences.
Metabolism, 54 (2005), pp. 748-755
A. Tremblay, N. Boulé, É. Doucet, S. Woods.
Is the insulin resistance syndrome the price to be paid to achieve body weight stability?.
Int J Obes (Lond), 29 (2005), pp. 1295-1298
N. Balcombe, D. Sinclair.
Ageing: definitions, mechanisms and the magnitude of the problem.
Best Pract Res Clin Gastroenterol, 15 (2001), pp. 835-849
K. Hughes, R. Reynolds.
Evolutionary and mechanistic theories of aging.
Annu Rev Entomol, 50 (2005), pp. 421-445
T.B.L. Kirkwood.
The origins of human ageing.
Phil Trans R Soc Lond B, 352 (1997), pp. 1765-1772
G.C. Williams.
Pleiotropy, natural selection, and the evolution of senescence.
Evolution, 11 (1957), pp. 398-411
V.P. Skulachev.
Programmed death phenomena: from organelle to organism.
Ann NY Acad Sci, 959 (2002), pp. 214-237
C. Zafon.
Ageing purpose: another thrifty genotype.
Med Hypotheses, 61 (2003), pp. 482-485
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