Abstract
Sarcopenia is characterized by a lower skeletal muscle quantity, higher fat accumulation in the muscle, lower muscle strength, and lower physical performance. The most commonly used, low cost and accessible methods to assess skeletal muscle mass include dual energy X-ray absorptiometry (DEXA), anthropometry and bioelectrical impedance analysis (BIA). Magnetic resonance imaging (MRI), computerized tomography (CT) and creatinine excretion are the most specific golden standards for assessing muscle mass or cross sectional muscle area. Other available measures include peripheral quantitative computerized tomography (pQCT), ultrasound and neutron activation. Skeletal muscle strength is another important component for the assessment of sarcopenia and muscle quality. Several methods are available for the measurement of muscle strength which include simple dynamometers to measure isometric strength and the most complex isokinetic strength measures of power and torque. Standardized physical performance measures complement the measures of muscle mass for the assessment of sarcopenia. A clinical definition of sarcopenia ought to use methods of assessment that are valid, reliable, specific to skeletal muscle, predictive of future health events, non-invasive, practical, low cost and widely accessible.
Sarcopenia is characterized by a lower skeletal muscle quantity, higher fat accumulation in the muscle, lower muscle strength, lower physical performance, and changes in circulating biological markers. Because sarcopenia has long-reaching definitions, there is a lack of standardized methodologies to assess sarcopenia resulting in inconsistencies in the literature, to the paucity of clinical trials of interventions which primarily target sarcopenia, and to the lack of therapeutic indications for sarcopenia that are accepted by the regulatory agencies in the US and Europe.
Methods for measuring skeletal muscle mass and imaging
The most commonly used, low cost and accessible methods to assess skeletal muscle mass include dual energy X-ray absorptiometry (DEXA), anthropometry and bioelectrical impedance analysis (BIA). Magnetic resonance imaging (MRI), computerized tomography (CT) and creatinine excretion are the most specific golden standards for assessing muscle mass or cross sectional muscle area. Other available measures include peripheral quantitative computerized tomography (pQCT), ultrasound and neutron activation. Table 1 summarizes the advantages and limitations of each of these measurement methods.
Table 1. Methods to assess skeletal muscle mass and muscle imaging.
Method | Advantages | Limitations | |
---|---|---|---|
Golden Standard |
Magnetic resonance imaging
(MRI) |
|
|
Computerized tomography
(CT) |
|
|
|
Creatinine excretion |
|
|
|
Widely Used Measures |
Dual energy X-ray
absorptiometry (DEXA) |
|
|
Bioelectrical impedance
analysis (BIA) |
|
|
|
Anthropometry |
|
|
|
Other Measures |
Peripheral quantitative
computerized tomography (pQCT) |
|
|
Ultrasound |
|
|
|
Neutron activation |
|
|
The DEXA is one of the most commonly used, widely available and low cost technologies for measuring body composition and muscle mass estimation. However, the accuracy of DEXA for assessing muscle mass in people of different age groups and in some pathological conditions may vary. For example, DEXA may overestimate muscle mass1 because it does not differentiate between water and bone-free lean tissue, and therefore may lead to an overestimate on muscle mass in older persons who have and extracellular fluid accumulation.2 Despite this limitation, DEXA provides valid estimates of appendicular skeletal muscle mass,3, 4 and skeletal muscle measures with DEXA are associated with prevalent and incident physical disability.5-8 Anthropometric measures and BIA are inexpensive and easy to assess, but have limited accuracy and validity.9-11
MRI and CT are considered the golden standard and the most accurate imaging methods to assess muscle mass, muscle cross sectional area and muscle quality as determined by muscle density and intramuscular fat infiltration. However, the high cost and the operational complexity limit their use in large clinical trials and clinical practice, although the new technology of low-field extremity MRI is allowing less expensive alternatives to this image modality. MRI and CT also assess adipose tissue, which is directly associated with intramuscular fat infiltrates, which in turn may impair muscle function and strength.12 The assessment of muscle density using MRI or CT provides a reliable and valid measure of the fatty degeneration of muscle tissue.13 A lower muscle density indicates a higher intramuscular fat content which may be detrimental for muscle function.
Urinary creatinine excretion is a specific indicator of total body skeletal muscle mass because creatine, which is the precursor of creatinine, originates almost exclusively from skeletal muscle. However, creatinine excretion varies during the day, which may affect the excretion estimate. In addition, this method requires to maintain the subject on a meat-free diet for a few days and a prolonged urine collection is needed.2
The pQCT uses a portable CT scanner to measure cross-sectional area and density of bone, muscle and adipose tissue of the extremities.12 B-mode ultrasonography is an alternative low cost methodology for assessing the muscle size of individual muscles, but this technique requires highly trained personnel.14 Another method to estimate the whole body muscle mass is the in vivo neutron activation analysis combined with the 40K whole body counting.15 This method is based on the difference in the potassium-to-nitrogen ratio between the skeletal muscle and the non-skeletal muscle tissues. If total body potassium (from the 40K whole body counting) and total body nitrogen (from prompt-γ neutron activation analysis) are known, these ratios can be derived and applied to predict the skeletal muscle mass. However, this method is expensive and needs to be validated compared to CT.1
Muscle strength
Skeletal muscle strength is another important component for the assessment of sarcopenia and muscle quality.10, 16, 17 Several methods are available for the measurement of muscle strength which include simple dynamometers to measure isometric strength and the most complex isokinetic strength measures of power and torque. In well-functioning older men and women enrolled in the Health Aging and Body Composition (Health ABC) study, the mid-thigh muscle area is associated with a higher risk of mobility disability, but such an association is not independent of lower knee extension strength and skeletal muscle density.18 In the same cohort, low muscle mass does not explain the strong relationship between strength and mortality, suggesting that muscle strength may be more important than muscle mass in estimating the risk of events.19 Hand grip and quadriceps strength have similar predictive value for mortality.19-21 In the InChianti cohort isometric hand grip strength is strongly correlated with lower extremity muscle power, knee extension torque, and calf cross-sectional muscle area,22 suggesting that sarcopenia is a systemic condition rather than being limited to single muscles or body compartments, such as lower extremities. Because muscle strength measures of various body compartments are highly correlated, these data also suggest that grip strength measured with a hand held dynamometer may be a good surrogate measure of other more complex measures of skeletal muscle strength in the lower extremities.
Physical performance
Standardized physical performance measures complement the measures of muscle mass for the assessment of sarcopenia.23 Physical performance measures are correlated with body composition and skeletal muscle parameters,24, 25 and predict relevant health-related outcomes, such as mortality, morbidity, institutionalization and disability.26-29 The Short Physical Performance Battery based on gait speed, chair stands and balance tests, 27 the 400 m walk test26 and the 6 min walk30 test are among the most widely used and validated measures. Other useful physical performance measures include the stair climb test,30 the lift and carry task,30 the car task,30 the Performance Activities of Daily Living (PADL),31 the task modification (MOD) scale for assessing compensatory strategies for completing daily tasks,32 the musculoskeletal impairment index,33 and the multidimensional physical performance test.34
Biological markers
The adipose tissue produces several pro-inflammatory cytokines, such as tumor necrosis factor (TNF-alpha), interleukin (IL-6), and IL-1, all of which are associated with aging, obesity and sarcopenia.35-37 The pro-inflammatory cytokines are involved with cachexia, anorexia of aging,38 and are detrimental to the skeletal muscle.39 Several studies have shown independent associations of pro-inflammatory cytokines with lower muscle strength, lower physical performance, and higher risk of disability in older persons.37, 40-43
Oxidative damage biomarkers have also relevant associations with sarcopenia. Oxidized low-density lipoprotein (oxLDL), a marker of lipoprotein peroxidation, is an independent predictor of incident mobility limitation.44 Protein carbonyls, markers of oxidative damage, are associated with lower grip strength in older adults.45, 46 On the other hand, antioxidants, such as intake of carotenoids and vitamin C, and plasma levels of alpha- and gamma-tocopherol are inversely associated with measures of sarcopenia.47-49
Several other biomarkers have shown significant associations with measures of sarcopenia. Anemia is associated with lower muscle strength and physical performance in older persons.50 Low serum albumin is associated with poor grip strength in older men and women.51 Low plasma selenium concentration is associated with reduced muscle strength.52 Higher circulating levels of uric acid are prospectively associated with higher handgrip and knee extension torque strength in older persons.53 Higher magnesium concentrations are significantly associated with indexes of muscle performance, including grip strength, lower-leg muscle power, knee extension torque, and ankle extension strength.54 Vitamin D plays an important role in the skeletal muscle metabolism, and persons with low serum 25-hydroxyvitamin D level have poor performance, poor muscle mass measured with DEXA, and diminished lower grip strength.55, 56
In summary, several studies have shown that pro-inflammatory cytokines, markers of oxidative damage and a broad range of other biomarkers have strong and independent associations with several measures of sarcopenia. However, such markers are also associated with a wide range of other diseases and conditions. Because these markers have little specificity for skeletal muscle and strength loss, they may have limited utility for the assessment of sarcopenia. The measurement of circulating ubiquitin proteasome57-59 and plasma caspase60 may be more specific markers of muscle protein breakdown, however, to our knowledge these circulating markers have not been studied in association with age-related sarcopenia.
Conclusions
Currently there is no standardized and established quantitative definition of sarcopenia based on skeletal muscle mass, strength and/or physical performance, which is used in clinical practice or as an accepted therapeutic indication. Once the standardized methodology for the clinical assessment of sarcopenia is established, normal and abnormal values of the measurement need to be determined. Normal values of biological or physiological measures can be based on cut-points from standard deviations of a reference population or on quantiles distribution in a population. A clinically more relevant approach to define sarcopenia should be based on cut-points of muscle mass or muscle quality levels determined by expert consensus according to the risk for future health-related events, such as mortality,19 morbidity or incidence of physical disablity.5
A clinical definition of sarcopenia ought to use methods of assessment that are valid, reliable, specific to skeletal muscle, predictive of future health events, non-invasive, practical, low cost and widely accessible. In this respect, sarcopenia expressed as muscle quality assessed by means of a combined measure of muscle mass with DEXA and measure of grip strength with a hand-held dynamometer seems a very promising approach, as both these methodologies share most of the abovementioned characteristics.
Acknowledgements
This work was supported by the University of Florida Institute on Aging and the Claude D. Pepper Older Americans Independence Center (NIH grant 1P30AG028740)
Reference List
- 1.Wang ZM, Visser M, Ma R, Baumgartner RN, Kotler D, Gallagher D, Heymsfield SB. Skeletal muscle mass: evaluation of neutron activation and dual-energy X-ray absorptiometry methods. J Appl Physiol. 1996 Mar;80(3):824–31. doi: 10.1152/jappl.1996.80.3.824. [DOI] [PubMed] [Google Scholar]
- 2.Proctor DN, O’Brien PC, Atkinson EJ, Nair KS. Comparison of techniques to estimate total body skeletal muscle mass in people of different age groups. Am J Physiol. 1999 Sep;277(3 Pt 1):E489–E495. doi: 10.1152/ajpendo.1999.277.3.E489. [DOI] [PubMed] [Google Scholar]
- 3.Levine JA, Abboud L, Barry M, Reed JE, Sheedy PF, Jensen MD. Measuring leg muscle and fat mass in humans: comparison of CT and dual-energy X-ray absorptiometry. J Appl Physiol. 2000 Feb;88(2):452–6. doi: 10.1152/jappl.2000.88.2.452. [DOI] [PubMed] [Google Scholar]
- 4.Visser M, Fuerst T, Lang T, Salamone L, Harris TB. Validity of fan-beam dual-energy X-ray absorptiometry for measuring fat-free mass and leg muscle mass. Health, Aging, and Body Composition Study--Dual-Energy X-ray Absorptiometry and Body Composition Working Group. J Appl Physiol. 1999 Oct;87(4):1513–20. doi: 10.1152/jappl.1999.87.4.1513. [DOI] [PubMed] [Google Scholar]
- 5.Janssen I, Baumgartner RN, Ross R, Rosenberg IH, Roubenoff R. Skeletal muscle cutpoints associated with elevated physical disability risk in older men and women. Am J Epidemiol. 2004 Feb 15;159(4):413–21. doi: 10.1093/aje/kwh058. [DOI] [PubMed] [Google Scholar]
- 6.Baumgartner RN, Wayne SJ, Waters DL, Janssen I, Gallagher D, Morley JE. Sarcopenic obesity predicts instrumental activities of daily living disability in the elderly. Obes Res. 2004 Dec;12(12):1995–2004. doi: 10.1038/oby.2004.250. [DOI] [PubMed] [Google Scholar]
- 7.Reid KF, Naumova EN, Carabello RJ, Phillips EM, Fielding RA. Lower extremity muscle mass predicts functional performance in mobility-limited elders. J Nutr Health Aging. 2008 Aug;12(7):493–8. doi: 10.1007/BF02982711. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Janssen I. Influence of sarcopenia on the development of physical disability: the Cardiovascular Health Study. J Am Geriatr Soc. 2006 Jan;54(1):56–62. doi: 10.1111/j.1532-5415.2005.00540.x. [DOI] [PubMed] [Google Scholar]
- 9.Fuller NJ, Hardingham CR, Graves M, Screaton N, Dixon AK, Ward LC, Elia M. Predicting composition of leg sections with anthropometry and bioelectrical impedance analysis, using magnetic resonance imaging as reference. Clin Sci (Lond) 1999 Jun;96(6):647–57. [PubMed] [Google Scholar]
- 10.Rolland Y, Lauwers-Cances V, Cournot M, Nourhashemi F, Reynish W, Riviere D, Vellas B, Grandjean H. Sarcopenia, calf circumference, and physical function of elderly women: a cross-sectional study. J Am Geriatr Soc. 2003 Aug;51(8):1120–4. doi: 10.1046/j.1532-5415.2003.51362.x. [DOI] [PubMed] [Google Scholar]
- 11.Heymsfield SB, McManus C, Smith J, Stevens V, Nixon DW. Anthropometric measurement of muscle mass: revised equations for calculating bone-free arm muscle area. Am J Clin Nutr. 1982 Oct;36(4):680–90. doi: 10.1093/ajcn/36.4.680. [DOI] [PubMed] [Google Scholar]
- 12.Cesari M, Leeuwenburgh C, Lauretani F, Onder G, Bandinelli S, Maraldi C, Guralnik JM, Pahor M, Ferrucci L. Frailty syndrome and skeletal muscle: results from the Invecchiare in Chianti study. Am J Clin Nutr. 2006 May;83(5):1142–8. doi: 10.1093/ajcn/83.5.1142. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Goodpaster BH, Kelley DE, Thaete FL, He J, Ross R. Skeletal muscle attenuation determined by computed tomography is associated with skeletal muscle lipid content. J Appl Physiol. 2000 Jul;89(1):104–10. doi: 10.1152/jappl.2000.89.1.104. [DOI] [PubMed] [Google Scholar]
- 14.Reeves ND, Maganaris CN, Narici MV. Ultrasonographic assessment of human skeletal muscle size. Eur J Appl Physiol. 2004 Jan;91(1):116–8. doi: 10.1007/s00421-003-0961-9. [DOI] [PubMed] [Google Scholar]
- 15.Cohn SH, Vartsky D, Yasumura S, Sawitsky A, Zanzi I, Vaswani A, Ellis KJ. Compartmental body composition based on total-body nitrogen, potassium, and calcium. Am J Physiol. 1980 Dec;239(6):E524–E530. doi: 10.1152/ajpendo.1980.239.6.E524. [DOI] [PubMed] [Google Scholar]
- 16.Goodpaster BH, Ward BK, Rossi A, Glynn NW, Delmonico MJ, Kritchevsky SB, Pahor M, Newman AB. Effects of Physical Activity on Strength and Skeletal Muscle Fat Infiltration in Older Adults: A Randomized Controlled Trial. J Appl Physiol. 2008 Sep 25; doi: 10.1152/japplphysiol.90425.2008. rd PJ. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Clark BC, Manini TM. Sarcopenia =/= dynapenia. J Gerontol A Biol Sci Med Sci. 2008 Aug;63(8):829–34. doi: 10.1093/gerona/63.8.829. [DOI] [PubMed] [Google Scholar]
- 18.Visser M, Goodpaster BH, Kritchevsky SB, Newman AB, Nevitt M, Rubin SM, Simonsick EM, Harris TB. Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons. J Gerontol A Biol Sci Med Sci. 2005 Mar;60(3):324–33. doi: 10.1093/gerona/60.3.324. [DOI] [PubMed] [Google Scholar]
- 19.Newman AB, Kupelian V, Visser M, Simonsick EM, Goodpaster BH, Kritchevsky SB, Tylavsky FA, Rubin SM, Harris TB. Strength, but not muscle mass, is associated with mortality in the health, aging and body composition study cohort. J Gerontol A Biol Sci Med Sci. 2006 Jan;61(1):72–7. doi: 10.1093/gerona/61.1.72. [DOI] [PubMed] [Google Scholar]
- 20.Willcox BJ, He Q, Chen R, Yano K, Masaki KH, Grove JS, Donlon TA, Willcox DC, Curb JD. Midlife risk factors and healthy survival in men. JAMA. 2006 Nov 15;296(19):2343–50. doi: 10.1001/jama.296.19.2343. [DOI] [PubMed] [Google Scholar]
- 21.Rantanen T, Guralnik JM, Foley D, Masaki K, Leveille S, Curb JD, White L. Midlife hand grip strength as a predictor of old age disability. JAMA. 1999 Feb 10;281(6):558–60. doi: 10.1001/jama.281.6.558. [DOI] [PubMed] [Google Scholar]
- 22.Lauretani F, Russo CR, Bandinelli S, Bartali B, Cavazzini C, Di IA, Corsi AM, Rantanen T, Guralnik JM, Ferrucci L. Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia. J Appl Physiol. 2003 Nov;95(5):1851–60. doi: 10.1152/japplphysiol.00246.2003. [DOI] [PubMed] [Google Scholar]
- 23.Newman AB, Kupelian V, Visser M, Simonsick E, Goodpaster B, Nevitt M, Kritchevsky SB, Tylavsky FA, Rubin SM, Harris TB. Sarcopenia: alternative definitions and associations with lower extremity function. J Am Geriatr Soc. 2003 Nov;51(11):1602–9. doi: 10.1046/j.1532-5415.2003.51534.x. [DOI] [PubMed] [Google Scholar]
- 24.Visser M, Kritchevsky SB, Goodpaster BH, Newman AB, Nevitt M, Stamm E, Harris TB. Leg muscle mass and composition in relation to lower extremity performance in men and women aged 70 to 79: the health, aging and body composition study. J Am Geriatr Soc. 2002 May;50(5):897–904. doi: 10.1046/j.1532-5415.2002.50217.x. [DOI] [PubMed] [Google Scholar]
- 25.Delmonico MJ, Harris TB, Lee JS, Visser M, Nevitt M, Kritchevsky SB, Tylavsky FA, Newman AB. Alternative definitions of sarcopenia, lower extremity performance, and functional impairment with aging in older men and women. J Am Geriatr Soc. 2007 May;55(5):769–74. doi: 10.1111/j.1532-5415.2007.01140.x. [DOI] [PubMed] [Google Scholar]
- 26.Newman AB, Simonsick EM, Naydeck EM, Kritchevsky SB, Nevitt M, Pahor M, Satterfield S, Brach JS, Studenski SA, Harris TB. Association of long-distance corridor walk performance with mortality, cardiovascular disease, mobility limitation, and disability. JAMA. 2006;295(17):2018–26. doi: 10.1001/jama.295.17.2018. [DOI] [PubMed] [Google Scholar]
- 27.Guralnik JM, Ferrucci L, Simonsick EM, Salive ME, Wallace RB. Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability. N Engl J Med. 1995;332(9):556–61. doi: 10.1056/NEJM199503023320902. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Cesari M, Kritchevsky SB, Penninx BWJH, Nicklas BJ, Simonsick EM, Newman AB, Tylavsky F, Brach JS, Satterfield S, Bauer DC, Visser M, Rubin S, Harris TB, Pahor M. Prognostic value of usual gait speed in well-functioning older people-results from the health, aging and body composition study. J Am Geriatr Soc. 2005;53:1675–80. doi: 10.1111/j.1532-5415.2005.53501.x. [DOI] [PubMed] [Google Scholar]
- 29.Rolland Y, Lauwers-Cances V, Cesari M, Vellas B, Pahor M, Grandjean H. Physical Performance Measures as Predictors of Mortality in a Cohort of Community-dwelling Older French Women. Eur J Epidemiol. 2006;21(2):113–22. doi: 10.1007/s10654-005-5458-x. [DOI] [PubMed] [Google Scholar]
- 30.Ettinger WH, Burns R, Messier SP, Applegate WB, Rejeski WJ, Morgan T, Shumaker S, Berry MJ, O’Toole M, Monu J, Craven T. The Fitness Arthritis and Seniors Trial (FAST): a randomized trial comparing aerobic exercise and resistance exercise to a health education program on physical disability in older people with knee osteoarthritis. JAMA. 1997;277:25–31. [PubMed] [Google Scholar]
- 31.Kuriansky JB, Gurland BJ, Fleiss JL. The assessment of self-care capacity in geriatric psychiatric patients by objective and subjective methods. J Clin Psychol. 1976 Jan;32(1):95–102. doi: 10.1002/1097-4679(197601)32:1<95::aid-jclp2270320129>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
- 32.Manini TM, Cook SB, VanArnam T, Marko M, Ploutz-Snyder L. Evaluating task modification as an objective measure of functional limitation: repeatability and comparability. J Gerontol A Biol Sci Med Sci. 2006 Jul;61(7):718–25. doi: 10.1093/gerona/61.7.718. [DOI] [PubMed] [Google Scholar]
- 33.Jette AM, Branch LG. Impairment and disability in the aged. J Chronic Dis. 1985;38(1):59–65. doi: 10.1016/0021-9681(85)90008-6. [DOI] [PubMed] [Google Scholar]
- 34.Reuben DB, Siu AL. An objective measure of physical function of elderly outpatients. The Physical Performance Test. J Am Geriatr Soc. 1990 Oct;38(10):1105–12. doi: 10.1111/j.1532-5415.1990.tb01373.x. [DOI] [PubMed] [Google Scholar]
- 35.Roubenoff R, Harris TB, Abad LW, Wilson PW, Dallal GE, Dinarello CA. Monocyte cytokine production in an elderly population: effect of age and inflammation. J Gerontol A Biol Sci Med Sci. 1998 Jan;53(1):M20–M26. doi: 10.1093/gerona/53a.1.m20. [DOI] [PubMed] [Google Scholar]
- 36.Cesari M, Kritchevsky SB, Baumgartner RN, Atkinson H, Penninx BWJH, Lenchik L, Palla S, Ambrosius WT, Tracy RP, Pahor M. Sarcopenia, obesity and inflammation – Results from theTrial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors study. Am J Clin Nutr. 2005;82:428–34. doi: 10.1093/ajcn.82.2.428. [DOI] [PubMed] [Google Scholar]
- 37.Visser M, Pahor M, Taaffe D, Goodpaster BH, Simonsick E, Newman AB, Nevitt MC, Harris TB. Relationship of interleukin-6 and tumor necrosis factor-á with muscle mass and muscle strength in elderly men and women: the Health ABC Study. J Gerontol A Biol Sci Med Sci. 2002;57:M326–M332. doi: 10.1093/gerona/57.5.m326. [DOI] [PubMed] [Google Scholar]
- 38.Bales CW, Ritchie CS. Sarcopenia, weight loss, and nutritional frailty in the elderly. Annu Rev Nutr. 2002;22:309–23. doi: 10.1146/annurev.nutr.22.010402.102715. Epub;%2002 Jan 4.:309-23. [DOI] [PubMed] [Google Scholar]
- 39.Anker SD, Ponikowski PP, Clark AL, Leyva F, Rauchhaus M, Kemp M, Teixeira MM, Hellewell PG, Hooper J, Poole-Wilson PA, Coats AJ. Cytokines and neurohormones relating to body composition alterations in the wasting syndrome of chronic heart failure. Eur Heart J. 1999 May;20(9):683–93. doi: 10.1053/euhj.1998.1446. [DOI] [PubMed] [Google Scholar]
- 40.Penninx BW, Kritchevsky SB, Newman AB, Nicklas BJ, Simonsick EM, Rubin S, Nevitt M, Visser M, Harris T, Pahor M. Inflammatory markers and incident mobility limitation in the elderly. J Am Geriatr Soc. 2004 Jul;52(7):1105–13. doi: 10.1111/j.1532-5415.2004.52308.x. [DOI] [PubMed] [Google Scholar]
- 41.Penninx BW, Abbas H, Ambrosius W, Nicklas BJ, Davis C, Messier SP, Pahor M. Inflammatory Markers and Physical Function Among Older Adults with Knee Osteoarthritis. J Rheumatol. 2004 Oct;31(10):2027–31. [PubMed] [Google Scholar]
- 42.Cesari M, Penninx BW, Pahor M, Lauretani F, Corsi AM, Guralnik JM, Ferrucci L. Inflammatory markers and physical performance in older persons: the InChianti study. J Gerontol A Biol Sci Med Sci. 2004;59:242–8. doi: 10.1093/gerona/59.3.m242. [DOI] [PubMed] [Google Scholar]
- 43.Ferrucci L, Harris TB, Guralnik JM, Wacholder S, Tracy RP, Corti MC, Penninx BWJH, Pahor M, Wallace RB, Havlik RJ. Inflammation, a novel risk factor for disability in older persons. J Am Geriatr Soc. 1999;47:639–46. doi: 10.1111/j.1532-5415.1999.tb01583.x. [DOI] [PubMed] [Google Scholar]
- 44.Cesari M, Kritchevsky SB, Nicklas BJ, Penninx BW, Holvoet P, Koh-Banerjee P, Cummings SR, Harris TB, Newman AB, Pahor M. Lipoprotein peroxidation and mobility limitation: results from the health, aging, and body composition study. Arch Intern Med. 2005 Oct 10;165(18):2148–54. doi: 10.1001/archinte.165.18.2148. [DOI] [PubMed] [Google Scholar]
- 45.Howard C, Ferrucci L, Sun K, Fried LP, Walston J, Varadhan R, Guralnik JM, Semba RD. Oxidative protein damage is associated with poor grip strength among older women living in the community. J Appl Physiol. 2007 Jul;103(1):17–20. doi: 10.1152/japplphysiol.00133.2007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 46.Semba RD, Ferrucci L, Sun K, Walston J, Varadhan R, Guralnik JM, Fried LP. Oxidative stress and severe walking disability among older women. Am J Med. 2007 Dec;120(12):1084–9. doi: 10.1016/j.amjmed.2007.07.028. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 47.Cesari M, Pahor M, Bartali B, Cherubini A, Penninx BW, Williams GR, Atkinson H, Martin A, Guralnik JM, Ferrucci L. Antioxidants and physical performance in elderly persons: the Invecchiare in Chianti (InCHIANTI) study. Am J Clin Nutr. 2004 Feb;79(2):289–94. doi: 10.1093/ajcn/79.2.289. [DOI] [PubMed] [Google Scholar]
- 48.Semba RD, Blaum C, Guralnik JM, Moncrief DT, Ricks MO, Fried LP. Carotenoid and vitamin E status are associated with indicators of sarcopenia among older women living in the community. Aging Clin Exp Res. 2003 Dec;15(6):482–7. doi: 10.1007/BF03327377. [DOI] [PubMed] [Google Scholar]
- 49.Semba RD, Lauretani F, Ferrucci L. Carotenoids as protection against sarcopenia in older adults. Arch Biochem Biophys. 2007 Feb 15;458(2):141–5. doi: 10.1016/j.abb.2006.11.025. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 50.Penninx BWJH, Pahor M, Cesari M, Corsi AM, Woodman RC, Guralnik JM, Ferrucci L. Anemia is associated with decreased physical performance and muscle strength in the elderly. J Am Geriatr Soc. 2004;52:719–24. doi: 10.1111/j.1532-5415.2004.52208.x. [DOI] [PubMed] [Google Scholar]
- 51.Schalk BW, Deeg DJ, Penninx BW, Bouter LM, Visser M. Serum albumin and muscle strength: a longitudinal study in older men and women. J Am Geriatr Soc. 2005 Aug;53(8):1331–8. doi: 10.1111/j.1532-5415.2005.53417.x. [DOI] [PubMed] [Google Scholar]
- 52.Lauretani F, Semba RD, Bandinelli S, Ray AL, Guralnik JM, Ferrucci L. Association of low plasma selenium concentrations with poor muscle strength in older community-dwelling adults: the InCHIANTI Study. Am J Clin Nutr. 2007 Aug;86(2):347–52. doi: 10.1093/ajcn/86.2.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 53.Macchi C, Molino-Lova R, Polcaro P, Guarducci L, Lauretani F, Cecchi F, Bandinelli S, Guralnik JM, Ferrucci L. Higher circulating levels of uric acid are prospectively associated with better muscle function in older persons. Mech Ageing Dev. 2008 Sep;129(9):522–7. doi: 10.1016/j.mad.2008.04.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 54.Dominguez LJ, Barbagallo M, Lauretani F, Bandinelli S, Bos A, Corsi AM, Simonsick EM, Ferrucci L. Magnesium and muscle performance in older persons: the InCHIANTI study. Am J Clin Nutr. 2006 Aug;84(2):419–26. doi: 10.1093/ajcn/84.1.419. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 55.Visser M, Deeg DJ, Lips P. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab. 2003 Dec;88(12):5766–72. doi: 10.1210/jc.2003-030604. [DOI] [PubMed] [Google Scholar]
- 56.Houston DK, Cesari M, Ferrucci L, Cherubini A, Maggio D, Bartali B, Johnson MA, Schwartz GG, Kritchevsky SB. Association between vitamin D status and physical performance: the InCHIANTI study. J Gerontol A Biol Sci Med Sci. 2007 Apr;62(4):440–6. doi: 10.1093/gerona/62.4.440. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 57.Roth SM, Metter EJ, Ling S, Ferrucci L. Inflammatory factors in age-related muscle wasting. Curr Opin Rheumatol. 2006 Nov;18(6):625–30. doi: 10.1097/01.bor.0000245722.10136.6d. [DOI] [PubMed] [Google Scholar]
- 58.Ishibashi Y, Hanyu N, Suzuki Y, Yanai S, Tashiro K, Usuba T, Iwabuchi S, Takahashi T, Takada K, Ohkawa K, Urashima M, Yanaga K. Quantitative analysis of free ubiquitin and multi-ubiquitin chain in colorectal cancer. Cancer Lett. 2004 Jul 28;211(1):111–7. doi: 10.1016/j.canlet.2004.01.028. [DOI] [PubMed] [Google Scholar]
- 59.Takada K, Nasu H, Hibi N, Tsukada Y, Shibasaki T, Fujise K, Fujimuro M, Sawada H, Yokosawa H, Ohkawa K. Serum concentrations of free ubiquitin and multiubiquitin chains. Clin Chem. 1997 Jul;43(7):1188–95. [PubMed] [Google Scholar]
- 60.Matulevicius S, Rohatgi A, Khera A, Das SR, Owens A, Ayers CR, Timaran CH, Rosero EB, Drazner MH, Peshock RM, de Lemos JA. The association between plasma caspase-3, atherosclerosis, and vascular function in the Dallas Heart Study. Apoptosis. 2008 Oct;13(10):1281–9. doi: 10.1007/s10495-008-0254-1. [DOI] [PubMed] [Google Scholar]