HomeLarge Type Edition
HOME ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text (PDF)
Services
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
PubMed
Right arrow PubMed Citation
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 58:M131-M137 (2003)
© 2003 The Gerontological Society of America

Anorexia and Weight Loss in Older Persons

John E. Morley

Division of Geriatric Medicine, Saint Louis University School of Medicine, and Geriatric Research, Education, and Clinical Center, VA Medical Center, St. Louis, Missouri.

"No fear can stand up to hunger, no patience can wear it out, disgust simply does not exist where hunger is...It's really easier to face bereavement, dishonour and perdition of one's soul than this kind of prolonged hunger." —Heart of Darkness, Joseph Conrad

Unintentional weight loss represents a cardinal symptom of frailty in older persons (1–6). Even a small decline in body mass in older persons is associated with mortality (7). Protein energy malnutrition is associated with anemia, pressure ulcers, sarcopenia, bone loss and hip fractures, declining immune function, impaired immune response to vaccinations, infections, cognitive impairment, functional decline, and poor quality of life (8–17). Weight loss is a sentinel event in long-term care facilities and associated with particularly poor outcomes (18,19). Despite this, aggressive nutritional management when weight loss is well established is often not associated with improved outcomes (20–24). For this reason, it is important that geriatricians increase their understanding of the pathophysiological processes that underlie weight loss in older persons (25) and increase their vigilance to detect early weight loss and institute-appropriate preventive and health promotion measures (26,27).

In this issue of the Journals, Paquet et al. (28) demonstrate the importance of emotional state on food intake in older persons undergoing geriatric rehabilitation. Positive emotions at the time of eating increased food intake, while anxiety, depression, and anger had negative effects on food intake. While previously depression has been shown to have a major negative effect on food intake (29,30), this study extends these findings to demonstrate that much smaller fluctuations of mood at the time of the meal produce major effects on the amount of food ingestion. de Castro (31) found that, in older persons living in the community, social facilitation at mealtimes and palatability were major factors in the amount eaten. He suggested that increasing the number of people present at a meal could enhance food intake. This was found to be true in persons receiving Meals on Wheels by Suda et al. (32), who found that when the meal deliverer stayed while the meal was eaten, nutritional risk and dysphoria were decreased.

When staff members spend more time feeding residents in the nursing home and utilize more verbal and physical prompts, food intake increased (33). Under these circumstances, it took an average of 38 minutes to feed a resident compared to 9 minutes under usual conditions. Because of the importance of food intake, it is critical that nursing staff are trained to be able to make accurate estimations of calorie intake in older persons (34).

Enhancing the environment in which meals are eaten has been shown to improve food intake (32). Older persons eat more in the morning (31), and this circadian shift is even more marked when they develop cognitive impairment (35). Thus, it is recommended that older persons receive more food at breakfast (36). Increasing palatability of meals later in the day also improves food intake (37). For these reasons, the Clinical Guide to Prevent and Manage Malnutrition in Long-Term Care provides a number of hints to improve social facilitation of eating at mealtime (38).

It has been suggested that weight loss is more likely to occur in older persons who are lifelong practitioners of dietary restraint, i.e., the intentional restriction of food intake to prevent weight gain (39,40). In some older persons, this has been associated with recurrence of anorexia nervosa toward the end of their life. In a normal-weight older population, Bathalon et al. (41,42) found no major differences between persons who practiced dietary restraint and those who did not. They did, however, have lower hemoglobin levels. Lower hemoglobin levels have been associated with an increase in frailty (43). Some older persons, when made aware of the studies on caloric restriction and longevity in animals, excessively restrain their food intake and develop malnutrition (44–48). Similarly, malnutrition is seen in older persons attempting to lower their cholesterol to prevent heart disease. This condition is known as "cholesterol phobia" (49). In 1988, we suggested that there was a physiological anorexia of aging that universally affected all older persons (50). The existence of a decline in caloric intake over the life span is now well established by multiple epidemiological studies (51). We postulated that this age-related physiological anorexia placed older persons at particular risk for developing malnutrition when they developed a disease process. Roberts et al. (52) showed that older persons had a deregulation of feeding regulation such that they struggled to alter their food intake either upward or downward in response to perturbations of body mass. Over the last decade, much research has explored the factors involved in the physiological regulation of food intake (53,54). As we originally postulated in the early 1980s, much of the normal feeding system is redundant, with multiple fail-safe mechanisms to ensure that hunger and the desire to intake continues and, therefore, that the individual survives (55).

The development of the physiological anorexia of aging appears to be predominantly due to altered gastric signals resulting in early satiation (56). With aging there is a decrease in the ability of the fundus to accommodate large volumes of food (57). This appears to be due to the failure of food in the fundus to release nitric oxide, resulting in a failure of smooth muscle relaxation (58,59). This leads to early antral filling, resulting in satiation signals being generated as the antral diameter increases (60,61). In addition, cholecystokinin, a gastrointestinal peptide that decreases hunger, circulates in higher levels in older compared to young persons (62,63) and is a more potent anorectic agent in older humans and other animals (64,65).

The role of antral nervous system neurotransmitters with aging is less clear and based predominantly on studies in rodents. The kappa opioid receptor modulator, dymorphin, has been shown to be less effective at increasing food intake in older rodents (66). However, a study in humans failed to demonstrate a clear effect of altered opioid tone in the pathogenesis of the anorexia of aging (67). Neuropeptide Y (NPY) is an important orexigenic agent. Older animals maintain their responsiveness to NPY stimulation of food intake (68), but have a reduction in NPY gene expression in response to starvation in older animals (69). Within the central nervous system, nitric oxide appears to play an important coordinating role in the production of feeding due to a variety of orexigenic neuropeptides such as orexin, neuropeptide Y, ghrelin, and agouti-related peptide (70,71). There is evidence that, with aging, there is a decline in the efficacy of the nitric oxide-synthesizing mechanisms related to feeding (59).

Leptin (from the Greek for "thin") is a peptide hormone produced by adipose cells that results in a decreased food intake and an increase in metabolic rate (72). With aging in men, there is a decline in testosterone levels (73–75), and this is associated with an increase in leptin levels out of proportion to fat loss in older males (76,77). However, another study failed to show a correlation between leptin levels and involuntary weight loss in older humans (78). This may be due, in part, to the development of leptin resistance with aging (79). In older animals, testosterone deficiency is associated with an increase in the anorectic peptide, cocaine-amphetamine-regulated transcript (CART) peptide, and a decrease in NPY, which could be reversed by the administration of testosterone (80).

Recently ghrelin, an orexigenic peptide produced by the fundus of the stomach, has been isolated (81). Its feeding-enhancing effects are antagonized by a metabolite of peptide YY, PYY3–36 (82). Peptide YY has been shown to produce weight loss when administered peripherally (83). Ghrelin also produces growth hormone release, which has been used to treat malnutrition in older persons (84,85). These agents may well prove to be important mediators of the gastric-induced satiation component of the anorexia of aging. The complex interactions of these neurotransmitters in the pathophysiology of the anorexia of aging are outlined in Figure 1. However, as pointed out in the pages of the Journals, long-term use of growth hormone is unlikely to enhance longevity (86–88).



View larger version (45K):
[in this window]
[in a new window]
  		Figure 1. Appetite regulation. MCH = melanin concentrating hormone; NPY = neuropeptide Y; CRF = corticotropin-releasing factor; AGRP = agoute-related peptide; CART = cocaine-amphetamine-regulated transcript; CCK = cholecystokinin; GLP-1 = glucagon-like peptide-1; GRP = gastric-related peptide; PYY = peptide YY; TNF = tumor necrosis factor; IL = interleukin; NO = nitric oxide

 
As so eloquently attested to by Blumenthal (89) in a recent issue of the Journals, the aging-disease dichotomy is often an inseparable conundrum. This is particularly true when anorexia and weight loss are accelerated in older persons when they develop one or more disease processes. Thus, cancer and end-stage heart disease can lead to "the cancer anorexia-cachexia syndrome" and the "cardiac cachexia syndrome," respectively (90–92). Cachexia is derived from the Greek words kakos meaning "bad" and hexis meaning "condition." The development of these cachexia syndromes appears to be related to the release of cytokines by the diseased tissues (93). Tumor necrosis factor {alpha}, interleukin-1, interleukin-6, and ciliary neurotropic factor appear to be particularly potent cytokines responsible for anorexia, muscle mass loss, and low albumin levels (94,95). Cytokines decrease albumin levels by decreasing production of albumin and producing extravariation of albumin outside of the intravascular space (95–97). In addition, cytokines activate nuclear factor kappa B, which reduces the formation of Myo D, and thus decrease muscle repair (98). Cytokines can produce their effects peripherally on multiple tissues, but they also produce effects on the central nervous system either directly by crossing the blood-brain barrier or secondarily by stimulating ascending fibers of the autonomic nervous system (99).

The majority of pathological causes of weight loss are reversible. For the clinician, these causes are easily remembered by using the "MEALS-ON-WHEELS" mnemonic (Table 1; 100). Depression is the major reversible cause of weight loss (28,30,101). Therapeutic diets remain a common cause of weight loss, and their utility in older persons, particularly those in nursing homes, continues to be of questionable value (102–104). If caloric supplements are to be used, they should be administered at least 1 hour before the meal or their major effect is mainly to reduce the size of the meal the elderly person would have eaten (105).


View this table:
[in this window]
[in a new window]
  		Table 1. MEALS-ON-WHEELS Mnemonic for Reversible Causes of Weight Loss

 
There is increasing enthusiasm for the use of orexigenic agents in the treatment of anorexia and weight loss in older persons. Megestrol acetate increases weight in older persons (106,107) most probably by decreasing cytokine production. Unfortunately, this is associated with a decline in testosterone levels, resulting in a decline in lean mass while increasing fat mass (108, and see 109 in this issue of the Journal). Testosterone can increase muscle mass in older persons (110,111), and its decline with aging is associated with a decline in muscle mass, strength, and functional status (112,113). Testosterone replacement may enhance function in older persons during rehabilitation (114).

Appetite stimulation and a feeling of general well-being are well-recognized effects of marijuana (115). Dronabinol, a cannabis derivative, is available and has been shown to enhance appetite and mood in patients with end-stage dementia, cancer, and AIDS (116–118). This agent can also inhibit vomiting and decrease pain, making it an excellent agent for use in end-of-life care (119). This drug appears to produce its effect through the endogenous CB1 cannabinol receptor. The function of endogenous cannabinoids is regulated by leptin (120).

The effects of the antiserotonergic agent, cyproheptadine, have been disappointing. Thalidomide inhibits cytokine release and may prove to be an excellent agent for treatment of cachexia syndromes (121). An approach to the development of drugs for the anorexia of aging is given in Figure 2.



View larger version (31K):
[in this window]
[in a new window]
  		Figure 2. Potential pharmacological approaches to treatment of anorexia and weight loss in older persons. NPY = neuropeptide Y; CRF = corticotropin-releasing factor; NSAIDS = nonsteroidal anti-inflammatory drugs; CCK = cholecystokinin; PYY = peptide YY

 
Weight loss is considered a sentinel event in nursing homes. Enormous strides have been made in the understanding of weight loss and anorexia over the last decade. Clinicians should be regularly screening for nutritional risk using tools such as the Mini-Nutritional Assessment Short Form (122), SCREEN [Seniors in the Community: Risk Evaluation for Eating and Nutrition] Questionnaire (123), or the Appetite Questionnaire (119). When older persons who are at nutritional risk are detected, the guidelines for nutritional management published in the Journals should be consulted (18).

Received October 14, 2002

Accepted October 15, 2002


   REFERENCES
Top
 REFERENCES
 

  1. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol Med Sci. 2001;56A:M146-M156.
  2. Gillick M. Pinning down frailty. J Gerontol Med Sci. 2001;56A:M134-M135.[Free Full Text]
  3. Zuliani G, Romagnoni F, Volpato S, et al. Nutritional parameters, body composition, and progression of disability in older disabled residents living in nursing homes. J Gerontol Med Sci. 2001;56A:M212-M216.[Abstract/Free Full Text]
  4. Newman AB, Gottdiener JS, McBurnie MA, et al. Associations of subclinical cardiovascular disease with frailty. J Gerontol Med Sci. 2001;56A:M158-M166.[Abstract/Free Full Text]
  5. Bortz WM II. A conceptual framework of frailty: a review. J Gerontol Med Sci. 2002;57A:M283-M288.[Abstract/Free Full Text]
  6. Morley JE, Perry HM III, Miller DK. Something about frailty. J Gerontol Med Sci. 2002;57A:M698-M704.[Free Full Text]
  7. Newman AB, Yanez D, Harris T, Duxbury A, Enright PL, Fried LP. Weight change in old age and its association with mortality. J Am Geriatr Soc. 2001;59:1309-1318.
  8. Wouters-Wesseling W, Rozendaal M, Snijder M, et al. Effect of a complete nutritional supplement on antibody response to influenza vaccine in elderly people. J Gerontol Med Sci. 2002;57A:M563-M566.[Abstract/Free Full Text]
  9. McElhaney JE. Nutrition, exercise, and influenza vaccination. J Gerontol Med Sci. 2002;57A:M555-M556.[Free Full Text]
  10. Reynish W, Andrieu S, Nourhashemi F, Vellas B. Nutritional factors and Alzheimer's disease. J Gerontol Med Sci. 2001;56A:M675-M680.[Abstract/Free Full Text]
  11. Amarantos E, Martinez A, Dwyer J. Nutrition and quality of life in older adults. J Gerontol. 2001;56:(Special Issue 2): 54-64.
  12. Coleman EA, Martau JM, Lin MK, Kramer AM. Pressure ulcer prevalence in long-term nursing home residents since the implementation of OBRA '87. J Am Geriatr Soc. 2002;50:728-732.[Medline]
  13. Chao D, Espeland MA, Farmer D, et al. Effect of voluntary weight loss on bone mineral density in older overweight women. J Am Geriat Soc. 2000;48:753-759.[Medline]
  14. MacIntosh C, Morley JE, Chapman IM. The anorexia of aging. Nutrition. 2000;16:983-995.[Medline]
  15. Thomas DR. Issues and dilemmas in the prevention and treatment of pressure ulcers: a review. J Gerontol Med Sci. 2001;56A:M328-M340.[Abstract/Free Full Text]
  16. Drewnowski A, Evans WJ. Nutrition, physical activity, and quality of life in older adults: summary. J Gerontol. 2001;56:(Special Issue 2): 89-94.
  17. Thomas DR. The critical link between health-related quality of life and age-related changes in physical activity and nutrition. J Gerontol Med Sci. 2001;56A:M599-M602.[Free Full Text]
  18. Thomas DR, Zdrowski CD, Wilson MM, Conright KC, Lewis C, Tariq S, Morley JE. Malnutrition in subacute care. Am J Clin Nutr. 2002;75:308-313.[Abstract/Free Full Text]
  19. Morley JE, Silver AJ. Nutritional issues in nursing home care. Ann Int Med. 1995;123:850-859.[Abstract/Free Full Text]
  20. Borum ML, Lynn J, Zhong ZS, et al. The effect of nutritional supplementation on survival in seriously ill hospitalized adults: an evaluation of the SUPPORT data. J Am Geriatr Soc. 2000;48:(5 Suppl S): S33-S38.[Medline]
  21. Callahan CM, Haag KM, Weinberger M, et al. Outcomes of percutaneous endoscopic gastrostomy among older adults in a community setting. J Am Geriatr Soc. 2000;48:1048-1054.[Medline]
  22. Ahronhein JC, Mulvihill M, Sieger C, Park P, Fries BE. State practice variations in the use of tube feeding for nursing home residents with severe cognitive impairment. J Am Geriatr Soc. 2001;49:148-152.[Medline]
  23. Gessert CE, Mosier MC, Brown EF, Frey B. Tube feeding in nursing home residents with severe and irreversible cognitive impairment. J Am Geriat Soc. 2000;48:1593-1600.[Medline]
  24. Mitchell SL, Tetroe JM. Survival after percutaneous endoscopic gastrostomy placement in older persons. J Gerontol Med Sci. 2000;55A:M735-M739.[Abstract/Free Full Text]
  25. Morley JE. Decreased food intake with aging. J Gerontol. 2001;56:(Special Issue 2): 81-88.
  26. Morley JE, Flaherty JH. It's never too late: health promotion and illness prevention in older persons. J Gerontol Med Sci. 2000;57A:M338-M342.[Free Full Text]
  27. Chernoff R. Nutrition and health promotion in older adults. J Gerontol. 2001;56:(Special Issue 2): 47-53.
  28. Paquet C. St. Arnaud McKenzie D, Kergoat M-J, Ferland G, Dube L. Direct and indirect effects of everyday emotions on food intake of elderly patients in institutions. J Gerontol Med Sci. 2003;58A:153-158.
  29. Morley JE, Kraenzle D. Causes of weight loss in a community nursing home. J Am Geriatr Soc. 1994;42:583-585.[Medline]
  30. Wilson MMG, Vaswani S, Liu D, Morley JE, Miller DK. Prevalence and causes of undernutrition in medical outpatients. Am J Med. 1998;104:56-63.[Medline]
  31. de Castro JM. Age-related changes in the social, psychological, and temporal influences on food intake in free-living, healthy, adult humans. J Gerontol Med Sci. 2002;57A:M368-M377.[Abstract/Free Full Text]
  32. Suda Y, Marske CE, Flaherty JH, Zdrodowski K, Morley JE. Examining the effect of intervention to nutritional problems of the elderly living in an inner city area: a pilot project. J Nutr Health Aging. 2001;5:118-123.[Medline]
  33. Simmons SF, Soterweil D, Schnelle JF. Improving food intake in nursing home residents with feeding assistance: a staffing analysis. J Gerontol Med Sci. 2001;56A:M790-M794.[Abstract/Free Full Text]
  34. Berrut G, Favreau AM, Dizo E, Tharreau B, Poupin C, Gueringuili M, Fressinaud P, Ritz P. Estimation of calorie and protein intake in aged patients: validation of a method based on meal portions consumed. J Gerontol Med Sci. 2002;57A:M52-M56.[Abstract/Free Full Text]
  35. Young KWH, Greenwood CE. Shift in diurnal feeding patterns in nursing home residents with Alzheimer's disease. J Gerontol Med Sci. 2001;56A:M700-M706.[Abstract/Free Full Text]
  36. Young KWH, Binns MA, Greenwood CE. Meal delivery practices do not meet needs of Alzheimer's patients with increased cognitive and behavioral difficulties in a long-term care facility. J Gerontol Med Sci. 2001;56A:M656-M661.[Abstract/Free Full Text]
  37. Mathey MFAM, Siebelink E, de Graaf C, Van Staveren WA. Flavor enhancement of food improves dietary intake and nutritional status of elderly nursing home residents. J Gerontol Med Sci. 2001;56A:M200-M205.[Abstract/Free Full Text]
  38. Thomas DR, Ashmen W, Morley JE, Evans WJ. Nutritional management in long-term care: development of a clinical guideline. J Gerontol Med Sci. 2000;55A:M725-M734.[Abstract/Free Full Text]
  39. Miller DK, Morley JE, Rubenstein LZ, Pietruszka FM. Abnormal eating attitudes and body image in older undernourished individuals. J Am Geriatr Soc. 1991;39:462-466.[Medline]
  40. Morley JE, Silver AJ, Miller DK, Rubenstein LZ. The anorexia of the elderly. Annals NY Acad Sci. 1989;575:50-58.[Medline]
  41. Bathalon GP, Hays NP, Meydani SN, et al. Metabolic, psychological, and health correlates of dietary restraint in healthy postmenopausal women. J Gerontol Med Sci. 2001;56A:M206-M211.[Abstract/Free Full Text]
  42. Hays NP, Bathalon GP, Roubenoff R, Lipman R, Roberts SB. The association of eating behavior with risk for morbidity in older women. J Gerontol Med Sci. 2002;57A:M128-M133.[Abstract/Free Full Text]
  43. Wilkinson TJ, Warren MR. Five-year survival of older people with anemia. J Am Geriatr Soc. 2002;50:1605.[Medline]
  44. Walford RL, Mock D, Verdery R, MacCallum T. Calorie restriction in biosphere 2: alterations in physiologic, hematolic, hormonal, and biochemical parameters in humans restricted for a 2-year period. J Gerontol Biol Sci. 2002;57A:B211-B224.[Abstract/Free Full Text]
  45. Lee IM, Blair SN, Allison DB, et al. Epidemiologic data on the relationships of caloric intake, energy balance, and weight gain over the life span with longevity and morbidity. J Gerontol. 2001;56:(Special Issue SI): 7-19.
  46. Moriguti JC, Das SK, Saltzman E, et al. Effects of a 6-week hypocaloric diet on changes in body composition, hunger, and subsequent weight regain in healthy young and older adults. J Gerontol Med Sci. 2000;55A:B580-B587.[Abstract/Free Full Text]
  47. Weindruch R, Kennan KP, Carney JM, et al. Caloric restriction mimetics: metabolic interventions. J Gerontol Med Sci. 2001;56A:20-33.[Abstract/Free Full Text]
  48. Poehlman ET, Turturro A, Bodkin N, et al. Caloric restriction mimetics: physical activity and body composition changes. J Gerontol Med Sci. 2001;56:(Special Issue): 45-54.[Abstract/Free Full Text]
  49. Morley JE, Morley PMK. Psychological and social factors in the pathogenesis of weight loss. Ann Rev Gerotol Geriatr. 1995;15:83-109.
  50. Morley JE, Silver AJ. Anorexia in the elderly. Neurobiol Aging. 1988;9:9-16.[Medline]
  51. Wakimoto P, Block G. Dietary intake, dietary patterns, and changes with age: an epidemiological perspective. J Gerontol. 2001;56:(Special Issue 2): 65-80.
  52. Roberts SB, Fuss P, Heyman MB, et al. Control of food intake in older men. JAMA. 1994;272:1601-1606.[Abstract/Free Full Text]
  53. Altman J. Weight in the balance. Neuroendocrinology. 2002;76:131-136.[Medline]
  54. Morley JE. Neuropeptide regulation of appetite and weight. Endocrine Rev. 1987;8:256-287.[Abstract/Free Full Text]
  55. Morley JE. The neuroendocrine control of appetite: the role of the endogenous opiates, cholecystokinin, TRH, gamma-amino-butyric-acid and the diazepam receptor. Life Sci. 1980;27:355-368.[Medline]
  56. Clarkston WK, Pantano MM, Morley JE, Horowitz M, Littlefield JM, Burton FR. Evidence for the anorexia of aging—gastrointestinal transit and hunger in healthy elderly vs. young adults. Am J Physiol. 1997;41:R243-R248.
  57. Rayner Ck, MacIntosh CG, Chapman IM, Morley JE, Horowitz M. Effects of age on proximal gastric motor and sensory function. Scandinavian. J Gastroenterology. 2000;35:1041-1047.
  58. Morley JE, Kumar VB, Mattammal MB, Farr S, Morley PM, Flood JF. Inhibition of feeding by a nitric oxide synthase inhibitor: effects of aging. Eur J Pharmacol. 1996;311:15-19.[Medline]
  59. Sun WM, Doran S, Jones KL, et al. Effects of nitroglycerin on liquid gastric emptying and antropyloroduodenal motility. Am J Physiol. 1998;275:(5 Pt 1): G1173-G1178.[Abstract/Free Full Text]
  60. Jones KL, Doran SM, Hveem K, et al. Relation between postprandial satiation and antral area in normal subjects. Am J Clin Nutr. 1997;66:127-132.[Abstract/Free Full Text]
  61. Morley JE. Anorexia, body composition, and ageing. Curr Opin Clin Nutr Metab Care. 2001;4:9-13.[Medline]
  62. MacIntosh CG, Horowitz M, Verhagen MAMT, et al. Effect of small intestinal nutrient infusion on appetite, gastrointestinal hormone release, and gastric myoelectrical activity in young and older men. Am J Gastroenterology. 2001;96:997-1007.[Medline]
  63. MacIntosh CG, Andrews JM, Jones KL, et al. Effects of age on concentrations of plasma cholecystokinin, glucagons-like peptide 1, and peptide YY and their relation to appetite and pyloric motility. Am J Clin Nutr. 1999;69:999-1006.[Abstract/Free Full Text]
  64. Silver AJ, Flood JF, Morley JE. Effect of gastrointestinal peptides of ingestion in old and young mice. Peptides. 1988;9:221-225.[Medline]
  65. MacIntosh CG, Morley JE, Wishart J, et al. Effect of exogenous cholecystokinin (CCK)-8 on food intake and plasma CCK, leptin, and insulin concentrations in older and young adults: evidence for increased CCK activity as a cause of the anorexia of aging. J Clin Endocrinol Metabol. 2001;86:5830-5837.[Abstract/Free Full Text]
  66. Gosnell BA, Levine AS, Morley JE. The effects of aging on opioid modulation of feeding in rats. Life Sci. 1983;32:2793-2799.[Medline]
  67. MacIntosh CG, Sheehan J, Davani N, Morley JE, Horowitz M, Chapman IM. Effects of aging on the opioid modulation of feeding in humans. J Am Geriatr Soc. 2001;49:1518-1524.[Medline]
  68. Morley JE, Hernandez EN, Flood JF. Neuropeptide Y increases food intake in mice. Am J Physiology. 1987;253:R516-R522.[Abstract/Free Full Text]
  69. Gruenewald DA, Marck BT, Matsumoto AM. Fasting-induced increases in food intake and neuropeptide Y gene expression are attenuated in aging male brown Norway rats. Endocrinology. 1996;137:4460-4467.[Abstract]
  70. Morley JE, Kumar VB, Mattammal M, Villareal DT. Measurement of nitric oxide synthase and its mRNA in genetically obese (ob/ob) mice. Life Sci. 1995;57:1327-1331.[Medline]
  71. Morley JE, Alshaher MM, Farr SA, Flood JF, Kumar VB. Leptin and neuropeptide Y (NPY) modulate nitric oxide synthase: further evidence for a role of nitric oxide in feeding. Peptides. 1999;20:595-600.[Medline]
  72. Morley JE, Pery HM, Baumgartner RP, Garry PJ. Commentary: Leptin, adipose tissue and aging—is there a role for testosterone? J Gerontol Biol Sci. 1999;54A:B108-B109.[Medline]
  73. Matsumoto AM. Andropause: clinical implications of the decline in serum testosterone levels with aging in men. J Gerontol Med Sci. 2002;57A:M76-M99.[Free Full Text]
  74. Morley JE, Kaiser FE, Perry HM III, et al. Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metab Clin Exper. 1997;46:410-413.[Medline]
  75. Feldman HA, Longcope C, Derby CA, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab. 2002;87:589-598.[Abstract/Free Full Text]
  76. Baumgartner RN, Waters DL, Morley JE, Patrick P, Montoya GD, Garry PJ. Age-related changes in sex hormones affect the sex difference in serum leptin independently of changes in body fat. Metab Clin Exper. 1999;48:378-384.[Medline]
  77. Baumgartner RN, Ross RR, Waters DL, et al. Serum leptin in elderly people: associations with sex hormones, insulin, and adipose tissue volumes. Obes Res. 1999;7:141-149.[Medline]
  78. Yukawa M, McCormick WC, Rajan S, et al. Leptin levels are appropriate for body mass index in older men who experience involuntary weight. J Am Geriatr Soc. 2002;50A:1566-1571.[Medline]
  79. Ma XH, Muzumdar R, Yang XM, Gabriely I, Berger R, Barzilai N. Aging is associated with resistance to effects of leptin on fat distribution and insulin action. J Gerontol Biol Sci. 2002;57A:B225-B231.[Abstract/Free Full Text]
  80. Sohn EH, Wolden-Hanson T, Matsumoto AM. Testosterone (T)-induced changes in arcuate nucleus cocaine-amphetamine-regulated transcript and NPY mRNA are attenuated in old compared to young male brown Norway rats: contribution of T to age-related changes in cocaine-amphetamine-regulated transcript and NPY gene expression. Endocrinology. 2002;143:954-963.[Abstract/Free Full Text]
  81. Muccioli G, Tschop M, Papotti M, Deghenghi R, Heiman M, Ghigo E. Neuroendocrine and peripheral activities of ghrelin: implications in metabolism and obesity. Eur J Pharmacol. 2002;440:234-254.
  82. Batterham RL, Cowley MA, Small CJ, et al. Gut hormone PYY (3–36) physiologically inhibits food intake. Nature. 2002;418:650-654.[Medline]
  83. Morley JE, Flood JF. An investigation of tolerance to the actions of leptogenic and anorexigenic drugs in mice. Life Sci. 1987;41:2157-2165.[Medline]
  84. Kaiser FE, Silver AJ, Morley JE. The effect of recombinant human growth hormone on malnourished older individuals. J Am Geriat Soc. 1991;39:235-240.[Medline]
  85. Chu LW, Lam KS, Tam SC, et al. A randomized controlled trial of low-dose recombinant human growth hormone in the treatment of malnourished elderly medical patients. J Clin Endocrinol Metab. 2001;86:1913-1920.[Abstract/Free Full Text]
  86. Bartke A, Coschigano K, Kopchick J, et al. Genes that prolong life: relationships of growth hormone and growth to aging and life span. J Gerontol Biol Sci. 2001;56A:B340-B349.[Abstract/Free Full Text]
  87. Butler RN, Fossel M, Harman SM, et al. Is there an antiaging medicine? J Gerontol Biol Sci. 2002;57A:B333-B338.[Abstract/Free Full Text]
  88. Olshansky SJ, Hayflick L, Carnes BA. Position statement on human aging. J Gerontol Biol Sci. 2002;57A:B292-B297.[Abstract/Free Full Text]
  89. Blumenthal HT. Future History: The aging-disease dichotomy: true or false? J Gerontol Med Sci. 2003;58A:138-145.
  90. Iniu A. Cancer anorexia-cachexia syndrome: current issues in research and management. CA Cancer J Clin. 2002;52:72-91.[Abstract/Free Full Text]
  91. Sharma R, Anker SD. Cardiac cachexia is a world-wide problem. Int J Cardiology. 1999;71:113-114.[Medline]
  92. Hamerman D. Molecular-based therapeutic approaches in treatment of anorexia of aging and cancer cachexia. J Gerontol Med Sci. 2002;57A:M511-M518.[Abstract/Free Full Text]
  93. Baez-Franceschi D, Morley JE. Physiopathology of the catabolism associated with malnutrition in the elderly [German]. Zeitschrift fur Gerontologie und Geriatrie. 1999;32:(1 Suppl 1): 12-19.
  94. Morley JE, Baumgartner RN, Roubenoff R, Mayer J, Nair KS. Sarcopenia. J Lab Clin Med. 2001;137:231-243.[Medline]
  95. Omran ML, Morley JE. Assessment of protein energy malnutrition in older persons, part II: laboratory evaluation. Nutrition. 2000;16:131-140.[Medline]
  96. Sullivan DH. What do the serum proteins tell us about our elderly patients? J Gerontol Med Sci. 2001;56A:M71-M74.[Free Full Text]
  97. Omran ML, Morley JE. Assessment of protein energy malnutrition in older persons, part I: History, examination, body composition, and screening tools. Nutrition. 2000;16:50-63.[Medline]
  98. Hughes SM, Koishi K, Rudnicki M, Maggs AM. MyoD protein is differentially accumulated in fast and slow skeletal muscle fibres and required for normal fibre type balance in rodents. Mechan Devel. 1997;61:151-163.
  99. Banks WA, Farr SA, La Scola ME, Morley JE. Intravenous human interleukin-1 alpha impairs memory processing in mice: dependence on blood-brain barrier transport into posterior division of the septum. J Pharmacol Exper Ther. 2001;299:536-541.[Abstract/Free Full Text]
  100. Morley JE. Why do physicians fail to recognize and treat malnutrition in older persons? J Am Geriatr Soc. 1994;42:1100-1102.[Medline]
  101. Blazer D. Depression in late life: review and commentary. J Gerontol Med Sci. 2003(2):M000–M000.
  102. Tariq SH, Karcic E, Thomas DR, et al. The use of a no-concentrated-sweets diet in the management of type 2 diabetes in nursing homes. J Am Dietetic Assoc. 2001;101:1463-1466.[Medline]
  103. Buckler DA, Kelber ST, Goodwin JS. The use of dietary restrictions in malnourished nursing home patients. J Am Geriatr Soc. 1994;42:1100-1102.
  104. Dorner B, Niedert KC, Welch PK. Position of the American Dietetic Association: liberalized diets for older adults in long-term care. J Am Dietetic Assoc. 2001;102:1316-1323.
  105. Wilson MMG, Purushothaman R, Morley JE. Effect of liquid dietary supplements on energy intake in the elderly. Am J Clin Nutr. 2002;75:944-947.[Abstract/Free Full Text]
  106. Karcic E, Philpot C, Morley JE. Treating malnutrition with megestrol acetate: literature review and review of our experience. J Nutr Health Aging. 2002;6:191-200.[Medline]
  107. Yeh SS, Wu SY, Levine DM, et al. The correlation of cytokine levels with body weight after megestrol acetate treatment in geriatric patients. J Gerontol Med Sci. 2001;56A:M48-M54.[Abstract/Free Full Text]
  108. Lambert CP, Sullivan DH, Freeling SA, Lindquist DM, Evans WJ. Effects of testosterone replacement and/or resistance exercise on the composition of megestrol acetate stimulated weight gain in elderly men: a randomized controlled trial. J Clin Endocrinol Metab. 2002;87:2100-2106.[Abstract/Free Full Text]
  109. Lambert CP, Sullivan DH, Evans WJ. Effects of testosterone replacement and/or resistance training on interleukin 6, tumor necrosis factor alpha, and leptin in elderly men ingesting megestrol acetate: a randomized controlled trial. J Gerontol Med Sci. 2003(2):M000–M000.
  110. Morley JE. Andropause: is it time for the geriatrician to treat it? J Gerontol Med Sci. 2001;56A:M263-M265.[Free Full Text]
  111. Kenny AM, Prestwood KM, Gruman CA, Marcello KM, Raisz LG. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. J Gerontol Med Sci. 2001;56A:M266-M272.[Abstract/Free Full Text]
  112. Baumgartner RN, Waters DL, Gallagher D, Morley JE, Garry PJ. Predictors of skeletal muscle mass in elderly men and women. Mechan Ageing Devel. 1999;107:123-136.
  113. Perry HM, Miller DK, Patrick P, Morley JE. Testosterone and leptin in older African-American men: relationship to age, strength, function, and season. Metab Clin Exper. 2000;49:1085-1091.[Medline]
  114. Bakhshi V, Elliott M, Gentili A, Godschalk M, Mulligan T. Testosterone improves rehabilitation outcomes in ill older men. J Am Geriatr Soc. 2000;48:550-553.[Medline]
  115. Morley JE, Logie P, Gensusan AD. The subjective effects of dagga: including comparative studies with Britain and America. S African Med J. 1973;47:1145-1149.
  116. Nelson K, Walsh D, Deeter P, et al. A phase Ii study of delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia. J Palliat Care. 1994;10:14-18.
  117. Volicer L, Stelly M, Morris J, McLaughlin J, Volicer BJ. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease. International J Geriatric Psychiatry. 1997;12:913-919.
  118. Reynolds R. Comparative efficacy of dronabinol and megestrol acetate. J Clin Oncology. 2002;20:2912-2913.[Free Full Text]
  119. Morley JE, Thomas DR, Wilson MMG. Appetite and orexigenic drugs. Ann Long Term Care 201;(Suppl II);1–12.
  120. DiMarzo V, Goparaju SK, Wang L, et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature. 2001;410:822-825.[Medline]
  121. Klausner JD, Makonkawkeyoon S, Akarasewi P, et al. The effect of thalidomide on the pathogenesis of human immunodeficiency virus type 1 and M tuberculosis infection. J AIDS Hum Retrovir. 1996;11:247-257.[Medline]
  122. Rubenstein LZ, Harker JO, Salva A, Guigoz Y, Vellas B. Screening for undernutrition in geriatric practice: developing the short-form mini-nutritional assessment (MNA-SF). J Gerontol Med Sci. 2001;56A:M366-M372.[Abstract/Free Full Text]
  123. Keller HH, McKenzie JD, Goy RE. Construct validation and test-retest reliability of the seniors in the community: risk evaluation for eating and nutrition questionnaire. J Gerontol Med Sci. 2001;56A:M552-M558.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Arch NeurolHome page
D. K. Johnson, C. H. Wilkins, and J. C. Morris
Accelerated weight loss may precede diagnosis in Alzheimer disease.
Arch Neurol, September 1, 2006; 63(9): 1312 - 1317.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
M.-M. G. Wilson and J. E. Morley
Invited Review: Aging and energy balance
J Appl Physiol, October 1, 2003; 95(4): 1728 - 1736.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Full Text (PDF)
Services
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
PubMed
Right arrow PubMed Citation

HOME ARCHIVE SEARCH TABLE OF CONTENTS