From the Chicago Meetings
Sarcopenia,☆☆

Presented at the Seventy-third Meeting of the Central Society for Clinical Research, Sept 21 through 23, 2000, Chicago, IL.
https://doi.org/10.1067/mlc.2001.113504Get rights and content

Abstract

Sarcopenia is a term utilized to define the loss of muscle mass and strength that occurs with aging. Sarcopenia is believed to play a major role in the pathogenesis of frailty and functional impairment that occurs with old age. Progressive muscle wasting occurs with aging. The prevalence of clinically significant sarcopenia is estimated to range from 8.8% in young old women to 17.5% in old old men. Persons who are obese and sarcopenic (the “fat frail”) have worse outcomes than those who are sarcopenic and non-obese. There is a disproportionate atrophy of type IIa muscle fibers with aging. There is also evidence of an age-related decrease in the synthesis rate of myosin heavy chain proteins, the major anabolic protein. Motor units innervating muscle decline with aging, and there is increased irregularity of muscle unit firing. There are indications that cytokines—especially interleukin-1β, tumor necrosis factor-α, and interleukin-6—play a role in the pathogenesis of sarcopenia. Similarly, the decline in anabolic hormones—namely, testosterone, dehydroepiandrosterone growth hormone, and insulin-like growth factor-I—is also implicated in the sarcopenic process. The role of the physiologic anorexia of aging remains to be determined. Decreased physical activity with aging appears to be the key factor involved in producing sarcopenia. An increased research emphasis on the factors involved in the pathogenesis of sarcopenia is needed. (J Lab Clin Med 2001;137:231-43)

Section snippets

Epidemiologic studies

The New Mexico group has developed methods for estimating the prevalence of sarcopenia and associations with risk factors and consequences in two studies of community-dwelling elderly populations in New Mexico. The first study is the New Mexico Aging Process Study, which consists of a cohort of approximately 400 elderly men and women who are being followed over time for the onset of sarcopenia, falls, morbidity, impairment, and disability.13 The second study is the New Mexico Elder Health

Future directions

These data suggest that many of the deleterious health and functional sequelae of old age are concentrated in a small group of people with sarcopenic-obesity. Because sarcopenic-obese, elderly individuals have increased body fat that masks their sarcopenia, they may not be recognized as “frail” unless muscle mass and strength are additionally measured.

Sarcopenia, obesity, and sarcopenic-obesity may be considered “syndromes of disordered body composition” that have different associations with

Age-related changes in muscle

Muscle accounts for approximately 40% of the total body mass and 75% of the body's cell mass.18 A quarter of all protein synthesis in the body occurs in muscle. There is a decrease in muscle mass and muscle strength with aging.19 In addition, there is a decline in age-related muscle efficiency (ie, muscle strength per unit of muscle mass).19, 20 This appears to be related to a decrease in total muscle fitness with aging with a disproportionate atrophy of the type IIa (fast-twitch) muscle fibers.

The role of cytokines in the development of sarcopenia

Loss of muscle with age may be caused by loss of anabolic factors such as neural growth factors, growth hormone, androgens and estrogens, and physical activity; by an increase in catabolic factors such as inflammatory cytokines; or by a combination of the two. The last is the most likely, but relatively little is currently known about the contribution of cytokines to the development of sarcopenia. It is clear that several of the cytokines are capable of causing muscle amino acid export in vivo

Anorexia of aging and sarcopenia

It is now well established that food intake declines with aging both in the general population and in highly healthy persons.51 The decline in food intake is greater in males than in females. The reasons for this physiologic decline in food intake are multiple and are reviewed briefly below. The role of this physiologic anorexia of aging in the pathogenesis of sarcopenia is uncertain.

The regulation of food intake is complex and involves both peripheral and central mechanisms.52 The major reason

Other nutritional factors and sarcopenia

There is now excellent evidence that homocystine levels increase with aging91 and that elevated homocystine levels are correlated with atherosclerosis.92 Peripheral vascular disease is associated with decreased lower limb function.93 Atherosclerosis is associated with accelerated blood flow to muscles and metabolic efficiency of muscles.94 Although deficiencies of both vitamin B12 and folate are associated with elevated homocystine level,95 it appears that they do not account for the majority

Hormones and sarcopenia

Both testosterone99, 100 and the adrenal androgens101 decline with age. There is epidemiologic evidence supporting the relationship of the fall in testosterone with the decline in muscle mass,17 muscle strength,17, 102 and functional status102 with aging. Interventional studies with testosterone have demonstrated an increase in muscle mass103 and an increase in upper arm strength.58, 104 One study suggested an increase in lower limb strength, but the study was not placebo controlled.105 Another

Exercise and sarcopenia

It is now well established that exercise, particularly that which increases mechanical force by strength training (resistance exercise), can increase muscle mass and strength even in very elderly persons.110 In elite Olympic oarsmen there was a decline in VO2 and in peak power. This decline was attenuated to some extent in those who continued to do regular aerobic training.111 Nelson et al112 demonstrated that high-intensity strength training exercises are an effective and feasible means to

Conclusion

The loss of muscle mass with aging represents a major cause of functional decline and disability. There is a paucity of data examining the pathogenesis of sarcopenia in older persons. The available data suggest that the pathogenesis of sarcopenia is multifactorial (Fig 5).

. The multifactorial origin of sarcopenia.

Intrinsic aging changes in the muscle and nerve represent one set of causes, but poor nutritional status, a decline in anabolic hormones and cytokines, and atherosclerosis all appear to

References (124)

  • AJ Silver et al.

    Effect of gastrointestinal peptides on ingestion in old and young mice

    Peptides

    (1988)
  • HM Perry et al.

    Body composition and age in African-American and caucasian women: relationship to plasma leptin levels

    Metabolism

    (1997)
  • RN Baumgartner et al.

    Age-related changes in sex hormones affect the sex difference in serum leptin independently of changes in body fat

    Metabolism

    (1999)
  • BA Gosnell et al.

    The effects of aging on opioid modulation of feeding in rats

    Life Sci

    (1983)
  • CR Plata-Salaman et al.

    Anorexia induced by chronic central administration of cytokines at estimated pathophysiological concentrations

    Physiol Behav

    (1996)
  • MJ Tisdale

    Wasting in cancer [review]

    J Nutr

    (1999)
  • MM Wilson et al.

    Prevalence and causes of undernutrition in medical outpatients

    Am J Med

    (1998)
  • J Fawcett et al.

    Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression [review]

    J Affect Disord

    (1998)
  • SS Yeh et al.

    Geriatric cachexia: the role of cytokines [review]

    Am J Clin Nutr

    (1999)
  • MR Nehler et al.

    Homocysteinemia as a risk factor for atherosclerosis: a review

    Cardiovasc Surg

    (1997)
  • JE Morley et al.

    Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men

    Metabolism

    (1997)
  • EL Schneider et al.

    The aging of America: impact on health care costs

    JAMA

    (1990)
  • JM Guralnik et al.

    Disability as a public health outcome in the aging population

    Annu Rev Public Health

    (1996)
  • D Gallagher et al.

    Appendicular skeletal muscle mass: effects of age, gender and ethnicity

    J Appl Physiol

    (1997)
  • RN Baumgartner et al.

    Cross-sectional age differences in body composition in persons 60+ years of age

    J Gerontol A Biol Sci Med Sci

    (1995)
  • RN Baumgartner et al.

    Human body composition and the epidemiology of chronic disease

    Obes Res

    (1995)
  • ME Mohs

    Assessment of nutritional status in the aged

  • JL Vittone et al.

    Muscle wasting in the elderly

    Age and Nutrition

    (1996)
  • LJ Launer et al.

    Body mass index, weight change, and risk of mobility disability in middle-aged and older women: the Epidemiologic Follow-up Study of NHANES I

    JAMA

    (1994)
  • JA Simoneau et al.

    Genetic determinism of fiber-type proportion in human skeletal muscle

    Faseb J

    (1995)
  • KE Ensrud et al.

    Correlates of impaired function in older women

    J Am Geriatr Soc

    (1994)
  • Bureau of the Census US

    Current population reports, series p-25

  • RN Baumgartner et al.

    Epidemiology of sarcopenia in elderly people in New Mexico

    Am J Epidemiol

    (1998)
  • Z Wang et al.

    Skeletal muscle mass: evaluation of neutron activation and dual energy X-ray absorptiometry methods

    J Appl Physiol

    (1996)
  • DN Proctor et al.

    Comparison of techniques to estimate total body skeletal muscle mass in people of different age groups

    Am J Physiol

    (1999)
  • RN Baumgartner et al.

    Predictors of skeletal muscle mass in elderly men and women

    Mech Ageing Dev

    (1999)
  • RS Lindle et al.

    Age and gender comparisons of muscle strength in 654 women and men aged 20-93 years

    J Appl Physiol

    (1997)
  • N Moller et al.

    Regulation of muscle mass and function: effects of aging and hormones

  • J Lexell

    Human aging, muscle mass, and fiber type composition [review]

    J Gerontol A Biol Sci Med Sci

    (1995)
  • M Foldvari et al.

    Association of muscle power with functional status in community-dwelling elderly women

    J Gerontol A Biol Sci Med Sci

    (2000)
  • G Grimby

    Muscle performance and structure in the elderly as studied cross-sectionally and longitudinally [review]

    J Gerontol A Biol Sci Med Sci

    (1995)
  • A Aniansson et al.

    Compensatory muscle fiber hypertrophy in elderly men

    J Appl Physiol

    (1992)
  • KR Short et al.

    The effect of age on protein metabolism: current opinion

    Clinical Nutrition and Metabolic Care

    (2000)
  • OE Rooyackers et al.

    Effect of age on in vivo synthesis rates of mitochondrial protein in human skeletal muscle

    Proc Natl Acad Sci USA

    (1996)
  • P Balagopal et al.

    Effects of aging on in vivo synthesis of skeletal muscle myosin heavy-chain and sarcoplasmic protein in humans

    Am J Physiol

    (1997)
  • J Andersen et al.

    Increase in the degree of coexpression of myosin heavy chain isoforms in skeletal muscle fibers of the very old

    Muscle Nerve

    (1999)
  • IG Brodsky et al.

    Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men: a clinical research center study

    J Clin Endocrinol Metab

    (1996)
  • RJ Urban et al.

    Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis

    Am J Physiol

    (1995)
  • KE Yarasheski et al.

    Effect of growth hormone and resistance exercise on muscle growth and strength in older men

    Am J Physiol

    (1995)
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    Supported in part by USDA Cooperative Agreement 58-1950-9-001 and National Institutes of Health Grant AG15797. The contents of this publication do not necessarily reflect the views or policies of the US Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

    ☆☆

    Reprint requests: John E. Morley, MB, BCh, Department of Medicine/Geriatrics, Saint Louis University School of Medicine, 1402 South Grand, Room M-238, St Louis, MO 63104.

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