Skip to main content

Advertisement

Log in

Endocrine and metabolic changes in human aging

  • Published:
Journal of the American Aging Association Aims and scope Submit manuscript

Abstract

Numerous alterations in hormonal secretion occur with aging. In general, these tend towards a disintegration of the normal cyclic secretory patterns resulting in lower total circulating levels. In addition, declines in receptors and postreceptor function further decreases the ability of the hormonal orchestra to maintain coordinated function throughout the organism. Clues to some of these age-related changes in humans may come from the study of simpler organisms where regulatory systems are known to modulate the aging process. In particular, the interactions among the environment, hormones, and insulin receptor genes have led to new insights into the genetic control of longevity and the development of syndrome X.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Mooradian, AD, Morley JE, and Korenman SG: Endocrinology in aging. Dis. Mon., 34:393–461, 1988.

    PubMed  CAS  Google Scholar 

  2. Baumgartner, RN, Waters, DL, Gallagher, D, Morley, JE, and Garry, PJ: Predictors of skeletal muscle mass in elderly men and women. Mech. Ageing Dev., 107: 123–36, 1999.

    PubMed  CAS  Google Scholar 

  3. Morley, JE, and Thomas, DR: Anorexia and aging: pathophysiology. Nutrition, 15:499–503, 1999.

    PubMed  CAS  Google Scholar 

  4. Baumgartner, RN, Ross, RR, Waters, DL, Brooks, WM, Morley, JE, Montoya, GD, and Garry, PJ: Serum leptin in elderly people: associations with sex hormones, insulin, and adipose tissue volumes. Obes. Res., 7:141–9, 1999.

    PubMed  CAS  Google Scholar 

  5. Friedman, EA: Advanced glycosylated end products and hyperglycemia in the pathogenesis of diabetic complications. Diabetes Care, 22:B65–71, 1999.

    PubMed  Google Scholar 

  6. Morley, JE: Geriatrics, in Yearbook of Endocrinology, 1993, edited by Bagdade JD, St. Louis, Mosby, 1993, pp. 61–65.

    Google Scholar 

  7. Snowdon, DA, Kane, RL, Beeson, WL, Burke, GL, Sprafka, JM, Potter, J, Iso, H, Jacobs DR Jr, and Phillips, RL: Is early natural menopause a biologic marker of health and aging? Am. J. Public Health, 79:709–14, 1989.

    PubMed  CAS  Google Scholar 

  8. Notelowitz, M: Menopause, in Endocrinology of Aging, edited by Morley, JE, VandenBerg, L, Totowa, NJ, Humana Press, 2000, pp. 161–181.

    Google Scholar 

  9. Sullivan, JM, and Fowlkes, LP: The clinical aspects of estrogen and the cardiovascular system. Obstet. Gynecol., 87: 36S–43S, 1996.

    PubMed  CAS  Google Scholar 

  10. Prouder, AJ, Ahmed, Al, and Crook, D: Hormone replacement therapy and serum angiotensin-converting enzyme activity in postmenopausal women. Lancet, 346:89–90, 1995.

    Google Scholar 

  11. Newcomb, PA, and Storer, BE: Postmenopausal hormone use and risk of large bowel cancer. J. Natl. Cancer Inst., 87:1067–1071, 1995.

    PubMed  CAS  Google Scholar 

  12. Flynn, BL: Pharmacologic management of Alzheimer disease, Part I: Hormonal and emerging investigational drug therapies. Ann. Pharmacother., 33:178–87, 1999.

    PubMed  CAS  Google Scholar 

  13. Birge, SJ: Is there a role for estrogen replacement therapy in the prevention and treatment of dementia? J. Am. Geriatr. Soc., 44:865–70, 1996.

    PubMed  CAS  Google Scholar 

  14. Flood, JF, and Morley, JE: Learning and memory in the SAMP8 mouse. Neurosci. Biobehav. Rev., 22: 1–20, 1998.

    PubMed  CAS  Google Scholar 

  15. Henderson, BE, Paganini-Hill, A, and Ross, RK: Decreased mortality in users of estrogen replacement therapy. Arch. Intern. Med., 151:75–78, 1991.

    PubMed  CAS  Google Scholar 

  16. Gray, A, Berlin, JA, McKinlay, JB, and Longcope C: An examination of research design effects on the association of testosterone and male aging: results of a meta-analysis. J. Clin. Epidemiol., 44:671–84, 1991.

    PubMed  CAS  Google Scholar 

  17. Morley, JE, Kaiser, FE, Perry, HM 3rd, Patrick, P, Morley, PM, Stauber, PM, Vellas, B, Baumgartner, RN, and Garry PJ: Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metabolism, 46:410–13, 1997.

    PubMed  CAS  Google Scholar 

  18. Korenman, SG, Morley, JE, Mooradian, AD, Davis, SS, Kaiser, FE, Silver, AJ, Viosca, SP, and Garza, D: Secondary hypogonadism in older men: its relation to impotence. J. Clin. Endocrinol. Metab. 71:963–9, 1990.

    PubMed  CAS  Google Scholar 

  19. Morley, JE, and Perry, HM 3rd: Androgen deficiency in aging men. Med. Clin. North Am., 8: 1279–89, 1999.

    Google Scholar 

  20. Veldhuis, JD: Recent insights into neuroendocrine mechanisms of aging of the human male hypothalamic-pituitary-gonadal axis: J. Androl., 20:1–17, 1999.

    PubMed  CAS  Google Scholar 

  21. Pincus, SM, Veldhuis, JD, Mulligan, T, Iranmanesh, A, and Evans, WS: Effects of age on the irregularity of LH and FSH serum concentrations in women and men. Am. J. Physiol., 273:E989–95, 1997.

    PubMed  CAS  Google Scholar 

  22. Pincus, SM, Mulligan, T, Iranmanesh, A, Gheorghiu, S, Godschalk, M, and Veldhuis, JD: Older males secrete luteinizing hormone and testosterone more irregularly, and jointly more asynchronously, than younger males. Proc. Natl. Acad. Sci. USA, 93:14100–5, 1996.

    Google Scholar 

  23. Haji, M, Kato, KI, Nawata, H, and Ibayashi, H: Age-related changes in the concentrations of cytosol receptors for sex steroid hormones in the hypothalamus and pituitary gland of the rat. Brain Res., 204:373–86, 1980.

    Google Scholar 

  24. Krithivas, K, Yurgalevitch, SM, Mohr, BA, Wilcox, CJ, Batter, SJ, Brown, M, Longcope, C, McKinlay, JB, and Kantoff, PW: Evidence that the CAG repeat in the androgen receptor gene is associated with the age-related decline in serum androgen levels in men. J. Endocrinol., 162:137–42, 1999.

    PubMed  CAS  Google Scholar 

  25. Snyder, PJ, Peachey, H, Hannoush, P, Berlin, JA, Loh, L, Lenrow, DA, Holmes, JH, Dlewati, A, Santanna, J, Rosen, CJ, and Strom, BL: Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J. Clin. Endocrinol. Metab., 84:2647–53, 1999.

    PubMed  CAS  Google Scholar 

  26. Urban RJ: Effects of testosterone and growth hormone on muscle function. J. Lab. Clin. Med., 134: 7–10, 1999.

    PubMed  CAS  Google Scholar 

  27. Morley, JE, Perry, HM 3rd, Kaiser, FE, Kraenzle, D, Jensen, J, Houston, K, Mattammal, M, and Perry, HM Jr: Effects of testosterone replacement therapy in old hypogonadal males: a preliminary study. J. Am. Geriatr. Soc., 41:149–52, 1993.

    PubMed  CAS  Google Scholar 

  28. Sih, R, Morley, JE, Kaiser, FE, Perry, HM 3rd, Patrick, P, and Ross, C: Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J. Clin. Endocrinol. Metab., 82:1661–7, 1997.

    PubMed  CAS  Google Scholar 

  29. Urban, RJ, Bodenburg, YH, Gilkison, C, Foxworth, J, Coggan, AR, Wolfe, RR, and Ferrando, A: Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis. Am. J. Physiol., 269: E820–6, 1995.

    PubMed  CAS  Google Scholar 

  30. Snyder, PJ, Peachey, H, Hannoush, P, Berlin, JA, Loh, L, Holmes, JH, Dlewati, A, Staley, J, Santanna, J, Kapoor, SC, Attie, MF, Haddad, JG Jr, and Strom, BL. Effect of testosterone treatment on bone mineral density in men over 65 years of age. J. Clin. Endocrinol. Metab., 84:1966–72, 1999.

    PubMed  CAS  Google Scholar 

  31. Janowsky, JS, Oviatt, SK, and Orwoll, ES: Testosterone influences spatial cognition in older men. Behav. Neurosci., 108:325–32, 1994.

    PubMed  CAS  Google Scholar 

  32. Flood, JF, Farr, SA, Kaiser, FE, LaRegina, M, and Morley, JE: Age-related decrease of plasma testosterone in SAMP8 mice: replacement improves age-related impairment of learning and memory. Physiol. Behav., 57:669–73, 1995.

    PubMed  CAS  Google Scholar 

  33. Barrett-Connor, EL: Testosterone and risk factors for cardiovascular disease in men. Diabete. Metab., 21:156–61, 1995.

    PubMed  CAS  Google Scholar 

  34. Rosano, GM, Leonardo, F, Pagnotta, P, Pelliccia, F, Panina, G, Cerquetani, E, della Monica, PL, Bonfigli, B, Volpe, M, and Chierchia, SL: Acute anti-ischemic effect of testosterone in men with coronary artery disease. Circulation, 99:1666–70, 1999.

    PubMed  CAS  Google Scholar 

  35. Zhao, SP, Li, XP: The association of low plasma testosterone level with coronary artery disease in Chinese men. Int. J. Cardiol., 63:161–4, 1998.

    PubMed  CAS  Google Scholar 

  36. Hajjar, RR, Kaiser, FE, and Morley, JE: Outcomes of long-term testosterone replacement in older hypogonadal males: a retrospective analysis. J. Clin. Endocrinol. Metab., 82:3793–6, 1997.

    PubMed  CAS  Google Scholar 

  37. Perry, HM 3rd, Horowitz, M, Morley, JE, Patrick, P, Vellas, B, Baumgartner, R, and Garry, PJ: Longitudinal changes in serum 25-hydroxyvitamin D in older people. Metabolism, 48:1028–32, 1999.

    PubMed  CAS  Google Scholar 

  38. Jones, G, Strugnell, SA, and DeLuca, HF: Current understanding of the molecular actions of vitamin D. Physiol. Rev., 78:1193–231, 1998.

    PubMed  CAS  Google Scholar 

  39. Chapuy, MC, Arlot, ME, Delmas, PD, Meunier, PJ: Effect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women. BMJ, 308:1081–2, 1994.

    PubMed  CAS  Google Scholar 

  40. Labrie, F, Belanger, A, Cusan, L, Gomez, JL, and Candas, B: Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging. J. Clin. Endocrinol. Metab., 82: 2396–402, 1997.

    PubMed  CAS  Google Scholar 

  41. Flood, JF, Morley, JE, and Roberts, E: Memory-enhancing effects in male mice of pregnenolone and steroids metabolically derived from it. Proc. Natl. Acad. Sci. USA, 89:1567–1571, 1992.

    PubMed  CAS  Google Scholar 

  42. Daynes, RA, and Aranco, BA: Prevention and reversal of some age-associated changes in immunologic responses by supplemental dehydroepiandrosterone sulfate therapy. Aging Immun. Infect. Dis., 3:135–154, 1992.

    Google Scholar 

  43. Arlt, W, Callies, F, van Vlijmen, JC, Koehler, I, Reincke, M, Bidlingmaier, M, Huebler, D, Oettel, M, Ernst, M, Schulte, HM, and Allolio, B: Dehydroepiandrosterone replacement in women with adrenal insuffiency. N. Engl. J. Med., 341:1013–1020, 1999.

    PubMed  CAS  Google Scholar 

  44. Morales, AJ, Haubrich, RH, Hwang, JY, Asakura, H, and Yen, SS: The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women. Clin. Endocrinol. (Oxf)., 49:421–32, 1998.

    CAS  Google Scholar 

  45. Morales, AJ, Nolan, JJ, Nelson, JC, and Yen, SS. Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J. Clin Endocrinol. Metab., 78:1360–7, 1994.

    PubMed  CAS  Google Scholar 

  46. Barnhart, KT, Freeman, E, Grisso, JA, Rader, DJ, Sammel, M, Kapoor, S, Nestler, JE: The effect of deydroepiandrosterone supplementation to symptomatic perimenopausal women on serum endocrine profiles, lipid parameters, and health-related quality of life. J. Clin. Endocrinol. Metab., 84:3896–3902, 1999.

    PubMed  CAS  Google Scholar 

  47. Morley, JE, Kaiser, F, Raum, WJ, Perry, M 3rd, Flood, JF, et al. Potentially predictive and manipulable blood serum correlates of aging in the healthy human male: progressive decreases in bioavailable testosterone, dehydroepiandrosterone sulfate. Proc. Natl. Acad. Sci. USA, 94:7537–7542, 1997.

    PubMed  CAS  Google Scholar 

  48. McGavack, TH, Chevalley, J, and Weissberg, J: The use of D5 pregnenolone in various clinical disorders. J. Clin. Endocrinol. Metab., 11:559–577, 1951.

    PubMed  CAS  Google Scholar 

  49. Flood, JF, Morley, JE, and Roberts, E: Pregnenolone sulfate enhances post-training memory processes when injected in very low doses into limbic system structures: the amygdala is by far the most sensitive. Proc. Natl. Acad. Sci. USA, 92:10806–10, 1995.

    Google Scholar 

  50. Steiger, A, Trachsel, I, Guldner, J, Hemmeter, U, Rothe, B, Rupprecht, R, Vedder, H, Holsboer, F: Neurosteroid pregnenolone induces sleep-EEG changes in man compatible with inverse agonistic GABAA-receptor modulation. Brain Res., 615:267–274, 1993.

    PubMed  CAS  Google Scholar 

  51. Pincus, G, Hoagland, H, Wilson, CH, and Fay, NJ: Effects on industrial production of the administration of 5 pregnenolone to factory workers, II. Psychosom. Med. 7:342–346, 1945.

    Google Scholar 

  52. Sih, R, Morley, JE, Kaiser, FE, and Herning, M: Effects of pregnenolone on aging. J. Investig. Med. 45:348A, 1997.

    Google Scholar 

  53. Rudman, D: Growth hormone, body composition, and aging. J. Am. Geriatr. Soc., 33:800–7, 1985.

    PubMed  CAS  Google Scholar 

  54. Lieberman, SA, and Hoffman, AR: The somatopause: should growth hormone deficiency in older people be treated? Clin. Geriatr. Med., 13:671–84, 1997.

    PubMed  CAS  Google Scholar 

  55. Kaiser, FE, Silver, AJ, and Morley, JE: The effect of recombinant human growth hormone on malnourished older individuals. J. Am. Geriatr. Soc., 39:235–40, 1991.

    PubMed  CAS  Google Scholar 

  56. Demling, R: Growth hormone therapy in critically ill patients. N. Engl. J. Med., 341:837–9, 1999.

    PubMed  CAS  Google Scholar 

  57. Margulis, L: Genetic and evolutionary consequences of symbiosis. Exp. Parasitol., 39:277–349, 1976.

    PubMed  CAS  Google Scholar 

  58. Margulis, L: Symbiosis and evolution. Sci. Am., 225:48–57, 1971.

    PubMed  CAS  Google Scholar 

  59. Hayflick, L: Aging, longevity, and immortality in vitro. Exp. Gerontol., 27:363–8, 1992.

    PubMed  CAS  Google Scholar 

  60. Vijg, J, and Wei, JY: Understanding the biology of aging: the key to prevention and therapy. J. Am. Geriatr. Soc. 43:426–34, 1995.

    PubMed  CAS  Google Scholar 

  61. Ashok, BT, and Ali R: The aging paradox: free radical theory of aging. Exp. Gerontol., 34:293–303, 1999.

    PubMed  CAS  Google Scholar 

  62. Veldhuis, JD: Recent insights into neuroendocrine mechanisms of aging of the human male hypothalamic-pituitary-gonadal axis. J. Androl., 20:1–17, 1999.

    PubMed  CAS  Google Scholar 

  63. Morley, JE: Anorexia of aging: physiologic and pathologic. Am. J. Clin. Nutr., 66:760–73, 1997.

    PubMed  CAS  Google Scholar 

  64. Gosnell, BA, Levine, AS, and Morley, JE: The effects of aging on opioid modulation of feeding in rats. Life Sci., 32: 2793–9, 1983.

    PubMed  CAS  Google Scholar 

  65. Kavaliers, M, Teskey, GC, and Hirst, M: The effects of aging on day-night rhythms of kappa opiatemediated feeding in the mouse. Psychopharmacology (Berl)., 87:286–91, 1985.

    CAS  Google Scholar 

  66. Jahnberg, T: Gastric adaptive relaxation. Effects of vagal activation and vagotomy. An experimental study in dogs and in man. Scand. J. Gastroenterol. Suppl., 46:1–32, 1977.

    PubMed  CAS  Google Scholar 

  67. Desai, KM, Sessa, WC, and Vane, JR: Involvement of nitric oxide in the reflex relaxation of the stomach to accomodate food or fluid. Nature, 351:477–9, 1991.

    PubMed  CAS  Google Scholar 

  68. Jones, KL, Doran, SM, Hveem, K, Bartholomeusz, FD, Morley, JE, Sun, WM, Chatterton, BE, and Horowitz, M: Relation between postprandial satiation and antral area in normal subjects. Am. J. Clin. Nutr. 66:127–32, 1997.

    PubMed  CAS  Google Scholar 

  69. Cook, CG, Andrews, JM, Jones, KL, Wittert, GA, Chapman, IM, Morley, JE, and Horowitz, M: Effects of small intestinal nutrient infusion on appetite and pyloric motility are modified by age. Am. J. Physiol., 273: R755–61, 1997.

    PubMed  CAS  Google Scholar 

  70. Silver, AJ, Flood, JF, Morley, JE: Effect of gastrointestinal peptides on ingestion in old and young mice. Peptides, 9:221–5, 1988.

    PubMed  CAS  Google Scholar 

  71. Miyasaka, K, Kanai, S, Ohta, M, and Funakoshi, A: Aging impairs release of central and peripheral cholecystokinin (CCK) in male but not in female rats. J. Gerontol. A Biol. Sci. Med. Sci., 52:M14–8, 1997.

    PubMed  CAS  Google Scholar 

  72. James, WPT and Ralph, A. New understanding in obesity research. Proc. Nutr. Soc 58:385–393, 1999.

    PubMed  CAS  Google Scholar 

  73. Perry, HM 3rd, Morley, JE, Horowitz, M, Kaiser, FE, Miller, DK, and Wittert, G: Body composition and age in African-American and Caucasian women: relationship to plasma leptin levels. Metabolism, 46:1399–405, 1997.

    PubMed  CAS  Google Scholar 

  74. Morley, JE, Perry, HM 3rd, Baumgartner, RP, and Garry, PJ: Leptin, adipose tissue and aging—is there a role for testosterone? J. Gerontol. Ser. A Biol. Sci. Med. Sci., 54:B108–9, 1999.

    CAS  Google Scholar 

  75. Larsson, H, Elmstahl, S, Berglund, G, Ahren, B: Evidence for leptin regulation of food intake in humans. J. Clin. Endocrinol. Metab., 83:4382–5, 1998.

    PubMed  CAS  Google Scholar 

  76. Mott, JW, Wang, J, Thornton, JC, Allison, DB, Heymsfield, SB, and Pierson, RN, Jr: Relation between body fat and age in 4 ethnic groups. Am. J. Clin. Nutr., 69:1007–13, 1999.

    PubMed  CAS  Google Scholar 

  77. Silver, AJ, Guillen, CP, Kahl, MJ, and Morley, JE: Effect of aging on body fat. J. Am. Geriatr. Soc., 41:211–3, 1993.

    PubMed  CAS  Google Scholar 

  78. Wilson, MMG, Vaswani, S, Liu, D, Morley, JE, and Miller, DK. Prevalence and causes of undernutrition in medical outpatients. Am. J. Med., 104:56–63, 1998.

    PubMed  CAS  Google Scholar 

  79. Baez-Franceschi, D, and Morley, JE: Physiopathology of the catabolism associated with malnutrition in the elderly. Z. Gerontol. Geriatr. 32:12–19, 1999.

    Google Scholar 

  80. Morley, JE: The elderly Type 2 diabetic patient: special considerations. Diabet. Med., 15:S41–6, 1998.

    PubMed  Google Scholar 

  81. Sensi, M, Pricci F, Andreani, D, and DiMario U: Advanced nonenzymatic glycation endproducts (AGE): their relevance to aging and the pathogenesis of late diabetic complications. Diabetes Res. 16:1–9, 1991.

    PubMed  CAS  Google Scholar 

  82. Arner, P, Pollare, T, and Lithell, H: Different aetiologies of type 2 (non-insulin-dependent) diabetes mellitus in obese and non-obese subjects. Diabetologia, 34:483–487, 1991.

    PubMed  CAS  Google Scholar 

  83. Meneilly, GS, Elahi, D, Minaker, KL, Sclater, AL, Rowe, JW: Impairment of noninsulin-mediated glucose disposal in the elderly. J. Clin. Endocrinol. Metab., 63:566–571, 1989.

    Google Scholar 

  84. Meneilly, GS, Elliott, T, Tessier, D, Hards, L, Tildesley, H: NIDDM in the elderly. Diabetes Care, 19:1320–5, 1996.

    PubMed  CAS  Google Scholar 

  85. Miller, DK, Lui, LY, Perry, HM 3rd, Kaiser, FE, and Morley, JE: Reported and measured physical functioning in older inner-city diabetic African Americans. J. Gerontol. Ser. A Biol. Sci. Med. Sci., 54:M230–6, 1999.

    CAS  Google Scholar 

  86. Meneilly, GS: Pathophysiology of type 2 diabetes in the elderly. Clin. Geriatr. Med., 15:239–253, 1999.

    PubMed  CAS  Google Scholar 

  87. Ferrannini, E, Vichi, S., Beck-Nielsen, H, Laakso, M, Paolisso G, Smith, U. Insulin action and age. European Group for the Study of Insulin Resistance (EGIR). Diabetes, 45:947–53, 1996.

    PubMed  CAS  Google Scholar 

  88. Daniel, PM, Love, ER, and Pratt, OE: The effect of age upon the influx of glucose into the brain. J. Physiol. (London), 274:141–148, 1978.

    CAS  Google Scholar 

  89. De Vivo, DC, Trifiletti, RR, Jacobson, RI, Ronen GM, Behmand, RA, and Harik SI: Defective glucose transport across the blood-brain barrier as a cause of persistent hypoglycorrhacia, seizures, and developmental delay. N. Engl. J. Med., 325:703–709, 1991.

    PubMed  Google Scholar 

  90. Forbes, A, Elliott, T, Tildesley, H, Finegood, D, Meneilly, GS: Alterations in non-insulin-mediated glucose uptake in the elderly patient with diabetes. Diabetes 47:1915–9, 1998.

    PubMed  CAS  Google Scholar 

  91. Meneilly, GS, Milberg, WP, and Tuokko, H: Differential effects of human and animal insulin on the responses to hypoglycemia in elderly patients with NIDDM. Diabetes, 44:272–277, 1995.

    PubMed  CAS  Google Scholar 

  92. Banks, WA, Jaspan, JB, and Kastin, AJ: Selective, physiological transport of insulin across the blood-brain barrier: Novel demonstration by species-specific radioimmunoassays. Peptides, 18:1257–1262, 1997.

    PubMed  CAS  Google Scholar 

  93. Das, UN: GLUT-4, tumor necrosis factor, essential fatty acids and daf-genes and their role in insulin resistance and non-insulin dependent diabetes mellitus. Prostaglandins Leukot. Essent. Fatty Acids, 50:13–20, 1999.

    Google Scholar 

  94. Hekimi, S, Lakowski, B, Barnes, TM, Ewbank, JJ: Molecular genetics of life span in C. elegans: how much does it teach us? Trends Genet., 14:14–20, 1998.

    PubMed  CAS  Google Scholar 

  95. Kimura, KD, Tissenbaum, HA, Liu, Y, and Ruvkun, G: daf-2, an Insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science, 277:942–946, 1997.

    PubMed  CAS  Google Scholar 

  96. Kops, GJ, de Ruiter, ND, De Vries-Smits, AM, Powell, DR, Bos JL and Th. Burgering, BM: Direct control of the forkhead transcription factor AFX by protein kinase B. Nature, 398:630–634, 1999.

    PubMed  CAS  Google Scholar 

  97. Nakae, J, Park, B-C, and Accili, D: Insulin stimulates phosphorylation of the forkhead transcription factor FKHR on Serine 253 through a Wortmannin-sensitive pathway. J. Biol. Chem., 274:15982–15985, 1999.

    Google Scholar 

  98. Vanfleteren, JR, and De Vreese, A: The gerontogenes age-1 and daf-2 determine metabolic rate potential in aging Caenorhabditis elegans. FASEB J., 9:1355–61, 1995.

    PubMed  CAS  Google Scholar 

  99. Lakowski, B, and Hekimi, S: The genetics of caloric restriction in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA, 95:13091–6, 1998.

  100. Paolisso, G, Tagliamonte, MR, Rizzo, MR, and Giugliano, D: Advancing age and insulin resistance: new factors about an ancient history. Eur. J. Clin. Invest., 29:758–769, 1999.

    PubMed  CAS  Google Scholar 

  101. Taub, J, Lau, JF, Ma, C, Hahn, JH, Hoque, F, Rothblatt, J and Chalfie, M: A cytosolic catalase is needed to extend adult lifespan in C. elegans daf-C and clk-1 mutants. Nature, 399:162–166, 1999.

    PubMed  CAS  Google Scholar 

  102. Honda, Y, and Honda, S: The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. FASEB J., 13:1385–1393, 1999.

    PubMed  CAS  Google Scholar 

  103. Yasuda, K, Adachi, H, Fujiwara, Y, and Ishii, N. Protein carbonyl accumulation in aging dauer formation-defective (daf) mutants of Caenorhabditis elegans. J. Gerontol., 54:B47–51, 1999.

    CAS  Google Scholar 

  104. Banks, WA, Kastin, AJ, Huang, W, Jaspan, JB, and Maness, LM: Leptin enters the brain by a saturable system independent of insulin. Peptides, 17:305–311, 1996.

    PubMed  CAS  Google Scholar 

  105. Campfield, LA, Smith FJ, Guisez, Y, Devos, R, and Burn, P. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science, 269:546–549, 1995.

    PubMed  CAS  Google Scholar 

  106. Halaas, JL, Gajiwala, KS, Maffei, M, Cohen, SL, Chait, BT, Rabinowitz, D, Lallone, RL, Burley, SK, and Friedman, JM: Weight-reducing effects of the plasma protein encoded by the obese gene. Science, 269: 543–546, 1995.

    PubMed  CAS  Google Scholar 

  107. Pelleymounter, MA, Cullen, MJ, Baker, MB, Hecht, R, Winters, D, Boone, T, and Collins, F: Effects of the obese gene product on body weight regulation in ob/ob mice. Science, 269:540–543, 1995.

    PubMed  CAS  Google Scholar 

  108. Zhang, Y, Proenca, R, Maffel, M, Barone, M, Leopold, L, and Friedman, JM: Positional cloning of the mouse obese gene and its human homologue. Nature, 372:425–432, 1994.

    PubMed  CAS  Google Scholar 

  109. Banks, WA, DiPalma, CR, and Farrell CL: Impaired transport of leptin across the blood-brain barrier in obesity. Peptides, 20:1341–5, 1999.

    PubMed  CAS  Google Scholar 

  110. Corica, F, Allegra, A, Corsonello, A, Buemi, M, Calapai, G, Ruello, A, Nicita Mauro, V, and Ceruso, D: Relationship between plasma leptin levels and the tumor necrosis factor-alpha system in obese subjects. Int. J. Obes. Relat. Metab. Disord., 23:355–60, 1999.

    PubMed  CAS  Google Scholar 

  111. Paolisso, G, Rizzo, MR, Mazziotti, G, Tagliamonte, MR, Gambardella, A, Rotondi, M, Carella, C, Giugliano, D, Varricchio, M, and D’Onofrio, F: Advancing age and insulin resistance: role of plasma tumor necrosis factor-α. Am. J. Physiol., 275:E294–299, 1998.

    PubMed  CAS  Google Scholar 

  112. Nilsson, J, Jovinge, S, Niemann, A, Reneland, R, and Lithell, H: Relation between plasma tumor necrosis factor-alpha and insulin sensitivity in elderly men with non-insulin-dependent diabetes mellitus. Arterioscler. Thromb. Vasc. Biol., 18:1199–202, 1998.

    PubMed  CAS  Google Scholar 

  113. Zinman, B, Hanley, AJ, Harris, SB, Kwan, J, and Fantus, IG: Circulating tumor necrosis factor-alpha concentrations in a native Canadian population with high rates of type 2 diabetes mellitus. J. Clin. Endocrinol. Metab., 84:272–8, 1999.

    PubMed  CAS  Google Scholar 

  114. Hube, F, Birgel, M, Lee, YM, and Hauner, H: Expression pattern of tumour necrosis factor receptors in subcutaneous and omental human adipose tissue: role of obesity and non-insulin-dependent diabetes mellitus. Eur. J. Clin. Invest. 29:672–8, 1999.

    PubMed  CAS  Google Scholar 

  115. Lang, CH, Dobrescu, C, and Bagby, GJ: Tumor necrosis factor impairs insulin action on peripheral glucose disposal and hepatic glucose output. Endocrinology, 130:43–52, 1992.

    PubMed  CAS  Google Scholar 

  116. Hotamisligil, GS: Mechanisms of TNF-alpha-induced insulin resistance. Exp. Clin. Endocrinol. Diabetes, 107:111–2, 1999.

    Google Scholar 

  117. Uysal, KT, Wiesbrock, SM, Marino, MW, and Hotamisligil, GS: Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature, 389:610–4, 1997.

    PubMed  CAS  Google Scholar 

  118. Cheung, AT, Ree, D, Kolls, JK, Fuselier, J, Coy, DH, and Bryer-Ash, M: An in vivo model for elucidation of the mechanism of tumor necrosis factor-alpha (TNF-alpha)-induced insulin resistance: evidence for differential regulation of insulin signaling by TNF-alpha. Endocrinology, 139:4928–35, 1998.

    PubMed  CAS  Google Scholar 

  119. Miles, PD, Romeo, OM, Higo, K, Cohen, A, Rafaat, K, and Olefskyk, JM: TNF-alpha-induced insulin resistance in vivo and its prevention by troglitazone. Diabetes, 46:1678–83, 1997.

    PubMed  CAS  Google Scholar 

  120. Hofmann, C, Lorenz, K, Braithwaite, SS, Colca, JR, Palazuk, BJ, Hotamisligil, GS, and Spiegelman, BM: Altered gene expression for tumor necrosis factor-alpha and its receptors during drug and dietary modulation of insulin resistance. Endocrinology, 134:264–70, 1994.

    PubMed  CAS  Google Scholar 

  121. Kwon, G, Xu, G, Marshall, CA, and McDaniel, ML: Tumor necrosis factor alpha-induced pancreatic beta-cell insulin resistance is mediated by nitric oxide and prevented by 15-deoxy-Delta12,14-prostaglandin J2 and aminoguanidine. A role for peroxisome proliferator-activated receptor gamma activation and inos expression. J. Biol. Chem., 274:18702–8, 1999.

    Google Scholar 

  122. Winkler, G, Lakatos, P, Salamon, F, Nagy, Z., Speer, G, Kovacs, M, Harmos, G, Dworak, O., and Cseh, K. Elevated serum TNF-alpha level as a link between endothelial dysfunction and insulin resistance in normotensive obese patients. Diabet. Med., 16:207–11, 1999.

    PubMed  CAS  Google Scholar 

  123. McKendrick, JD, Salas, E., Dube, GP, Murat, J., Russell, JC, and Radomski, MW: Inhibition of nitric oxide generation unmasks vascular dysfunction in insulin-resistant, obese JCR:LA-cp rats. Brit. J. Pharmacol., 124: 361–9, 1998.

    CAS  Google Scholar 

  124. Estrada, C, Gomez, C, Martin, C, Moncada, S, and Gonzalez C: Nitric oxide mediates tumor necrosis factor-α cytotoxicity in endothelial cells. Biochem. Biophys. Res. Commun., 186:475–482, 1992.

    PubMed  CAS  Google Scholar 

  125. Polte, T, and Schroder, H: Cyclic AMP mediated endothelial protection by nitric oxide. Biochem. Biophys. Res. Commun., 251:460–465, 1998.

    PubMed  CAS  Google Scholar 

  126. Baron, AD: The coupling of glucose metabolism and perfusion in human skeletal muscle. The potential role of endothelium-derived nitric oxide. Diabetes, 45:S105–9, 1996.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to W. A. Banks M.D..

About this article

Cite this article

Banks, W.A., Morley, J.E. Endocrine and metabolic changes in human aging. AGE 23, 103–115 (2000). https://doi.org/10.1007/s11357-000-0011-z

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11357-000-0011-z

Keywords

Navigation