Nestle Supplement 2

NUTRITION AND THE OLDER PERSON TABLE 8. Pathogenesis of Sarcopenia Genetic factors Low muscle mass at birth Physical inactivity Low calorie intake Low protein intake Insulin resistance Hypogonadism (men) Low growth hormone Low mechanogrowth factor Low vitamin D Myostatin Cytokine excess Loss of motor units Peripheral arterial disease Accumulation of fat in muscles decreases muscle power. This can occur due to either abnormalities in mitochondrial DNA that occur with aging or increased circulating triglycerides. These changes are strongly associated with insulin resistance. Testosterone levels decline with aging.26 Low testosterone levels with aging are associated with decreased muscle mass and falls.Testosterone replacement enhances muscle mass, strength, and physical performance. A preliminary study has suggested that together with an oral caloric supplement testosterone will decrease hospitalizations.27 The major effect of testosterone on muscle is to stimulate satellite cells and thus increase muscle repair. Nandrolone, an anabolic steroid, appears to have similar effects. This has led to the development of selective androgen receptor molecules (SARMs) that build muscle and bone without altering prostate function.They can be given orally. The first of these SARMs is ostarine, which specifically binds the androgen receptor. In rats, it promotes muscle growth and shrinks the prostate. It also restores bone in ovariectomized rats. In humans over the age of 60 years, when given for 3 months, ostarine increased fat-free mass and increased stair climb power. In contrast, dehydroepiandrosterone has no effects on muscle mass, strength, or fat. Growth hormone increases nitrogen retention and increases muscle mass but fails to increase strength. Ghrelin is a peptide hormone produced in the fundus of the stomach. It enhances food intake, increases growth 28 • DECEMBER 2007 hormone release, and improves memory. Ghrelin has been shown to increase human appetite and is a potentially potent orexigenic agent. There are 2 major forms of the human insulin growth factor-1 gene: IGF-1 and mechanogrowth factor (MGF). IGF-1 promotes muscle protein synthesis and is regulated by growth hormone. Mechanogrowth factor enhances satellite cell production and motor neuron unit number. It is increased by resistance exercise. Stem cell replacement of MGF in older rats rejuvenated the old muscle. Hypovitaminosis D is associated with a decline in muscular strength, falls, and disability.28 In persons with low vitamin D, vitamin D supplementation has been shown to improve strength and performance. Myostatin inhibits muscle growth by inhibiting satellite cell proliferation. In 24-month-old mice lacking myostatin there is increased muscle mass. Amgen (Thousand Oaks, Calif) has developed peptobodies to myostatin, which are in clinical trials to develop a muscle-enhancing agent. Cytokines (especially tumor necrosis factor alpha and interleukin-6) decrease muscle mass, strength, and physical performance. In addition, they result in anemia, loss of urinary albumin, osteopenia, anorexia, and extravasation of albumin into the extravascular space. Motor unit firing rate declines with aging. Ciliary neurotrophic factor appears to be able to reverse this effect in rats. Motor units decline more rapidly in persons with diabetes and metabolic syndrome. Both alpha-lipoic acid and topiramate can stimulate nerve regeneration. Atherosclerosis, which leads to muscle hypoxia, results in muscle wasting and decreased function. The factors involved in the pathogenesis of sarcopenia are outlined in Table 8. These factors are consistently promoting muscle catabolism through atrophy and apoptosis. Agents that slow down or reverse sarcopenia promote anabolism through promoting muscle hypertrophy and regeneration (Figure 2).The ubiquitin-protease system (the cell “death chamber”) plays a key role in removing proteins from cells and turning them into amino acids or short chain peptides. Mitochondrial damage results in apoptosis. EXERCISE The key to reversing sarcopenia is exercise. Older persons should always begin with resistance exercises followed by balance exercises before undertaking endurance exercise. This approach decreases the likelihood of falls. Exercise regimens for older persons should aim for at least 30 minutes 5 days a week.

Table of Contents Feed for the Digital Edition of Nestle Supplement 2

Nestle Supplement Table of Contents Introduction to Weight Loss in Older Persons Diagnosis and Management of Oropharyngeal Dysphagia in the Elderly The Danger of Weight Loss in the Elderly Nutrients and Frailty

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