By Austin Baraki<\/p>\n\n\n\n
Recall from our prior articles that a decline in skeletal muscle mass is just one criterion for sarcopenia; in addition, there must also be a loss of strength or physical performance (1). This second criterion was added because the relationship between muscle cross-sectional area (i.e. size<\/i>) and force production (i.e. strength<\/i>) is much less predictable with aging compared to younger individuals (1,2). In other words, aging results in much more rapid strength and power losses than changes in muscle size alone would predict, suggesting that there are changes in \u201cmuscle quality\u201d that occur independently <\/i>of changes in muscle mass (2,3). It turns out that muscle quality (i.e strength per unit mass) \u201cappears to be a stronger predictor of performance than strength, mass, or body composition alone in older adults\u201d (3). We\u2019ll begin this article by looking at a few factors affecting muscle quality, including neuromuscular changes, structural changes, muscle infiltration, mitochondrial dysfunction, and microvascular dysfunction.<\/p>\n\n\n\n Sarcomere structure and organization is another crucial determinant of muscle contractile function. Electron micrograph studies of older muscle have shown disordered myofibrils, damage (\u201cstreaming<\/i>\u201d) of the sarcomere Z-disks, and abnormal swelling of the sarcoplasmic reticulum, all of which impair contractile function (3,10,11). Furthermore, part of the sarcomere contractile force is transmitted via the extracellular matrix (ECM) \u201cscaffolding\u201d throughout muscle tissue. This ECM also undergoes unfavorable changes in aging, including excessive accumulation of collagen and altered elasticity that impairs efficient force transmission (3,12).<\/p>\n\n\n\n At this point we\u2019ve discussed several mechanisms by which muscle \u201cquality\u201d decreases independently of changes in size, impairing strength and function. Muscle quality appears to be at least as (if not even more) important than total muscle mass in older individuals, particularly when it comes to treating sarcopenia (more on this in part 4 – let\u2019s not get ahead of ourselves).<\/p>\n\n\n\n DIAGNOSIS OF SARCOPENIA<\/span><\/strong><\/p>\n\n\n\n Now that we\u2019ve thoroughly explored our definition of sarcopenia, how do we make the diagnosis in a real person?<\/span> Although it might be too obvious to miss in some patients, we still need a reproducible, objective diagnostic method. There have been a number of scientific \u201cworking groups\u201d (SIG, EWGSOP, IWGS, SCWD, NIH) all looking at this particular issue over the years, but unfortunately we still don\u2019t have an \u201coperational definition\u201d based on a uniform set of clinical diagnostic criteria (21,22). Depending on which criteria are used, estimated prevalence of sarcopenia in community-dwelling people over 60 years old can range from 3-52% (23)! This massive range shows how badly we need a more rigorous diagnostic method. In this section we\u2019ll take a look at the current modalities that have been studied.<\/p>\n\n\n\n A number of techniques have been examined for quantifying<\/em> skeletal muscle mass<\/span><\/strong> (criterion #1). We can measure total skeletal muscle mass<\/span> and compare to young, healthy controls, or measure just the appendicular<\/span> (arms\/legs) lean mass (ALM), and normalize the value for height or BMI (ALM\/height2<\/sup> or ALM\/BMI) (1,22). In choosing among the available measurement techniques, we must consider their accuracy, precision, reproducibility, sensitivity to change over time, and accessibility (7). The 4-Compartment method (4C), CT scanning, and MRI are considered the \u201cgold standard\u201d methods for assessment of skeletal muscle mass (1,2,3,24). CT and MRI can accurately assess cross-sectional areas, volumes, muscle densities and fatty\/fibrotic infiltration. However, these methods are very expensive, limited in availability, and CT scanning adds risks of radiation exposure.<\/p>\n\n\n\n Dual X-ray Absorptiometry<\/span> (DXA or DEXA)<\/strong> scanning is a rapid, inexpensive, and low-radiation scanning modality already used in research and clinical settings (e.g. osteoporosis screening) to distinguish soft tissues and bone (1,2,3,24). DXA has been shown to closely correlate with MRI, CT and 4C measurements, and an added benefit is that it could be used for simultaneous<\/span> screening of sarcopenia and osteopenia\/osteoporosis since many women already get osteoporosis screening at 65 or older. While DXA is a very promising tool, it does have one major weakness: it cannot detect fat infiltration or fibrosis to assess muscle quality<\/span> (3). This is important given our discussion so far showing why muscle size isn\u2019t everything in older people!<\/p>\n\n\n\n Skeletal muscle ultrasound<\/span> is a cheap, widely available, and very promising technique for imaging-based assessments of muscle size and quality <\/em>(2,3,24). It is an accurate and reliable method to measure muscle CSA, thickness, volume, and it can even provide a look at fatty\/fibrotic infiltration by way of echo intensity (3). Interestingly, some evidence shows that hypertrophic changes in muscle may be visualized by ultrasound even before they appear on DXA (3)! This could make serial ultrasound assessments valuable in tracking the response to interventions over time. Of course, this technique is impractical for measuring total<\/em> muscle mass (we wouldn\u2019t ultrasound every muscle in the body<\/em>), so perhaps further research could use a few major muscle groups to establish reference values for whole-body correlation, or we could just use it as a tool for quick follow-up evaluations.<\/p>\n\n\n\n A few other techniques have been suggested, but are unlikely to play a major role anytime soon so I\u2019ll only mention them briefly here. Electrical Impedance Myography<\/span> (not to be confused with Bioimpedance Analysis) is a painless and noninvasive technique based on applying electrical currents to specific muscles (3). It can detect changes in muscle quality due to fatty\/fibrotic infiltration and has already been validated in patients with Amyotrophic Lateral Sclerosis (ALS, Lou Gehrig\u2019s disease), and could be a useful adjunct method in the future. Motor Unit Number Index<\/span> (MUNIX) is a similar technique using rapid surface EMG measurements to estimate the number of motor units<\/span> in a given muscle (another factor in muscle quality). It has already been validated for long-term use in ALS patients and has also been used in sarcopenia studies (5). In contrast, Bioimpedance Analysis is a popular, simple, and cheap test used to measure body composition, but it is a very unreliable and insensitive test due to the effects of fluid status and other physiologic parameters (24). Although some organizations have suggested it might be useful as a rapid, portable screening tool, it appears to be unnecessary for screening given the other tools we have available, and is not sensitive or accurate enough for diagnostic use either.<\/p>\n\n\n\n Muscle strength<\/span><\/strong> (part of criterion #2) is a more straightforward assessment in the clinical setting, and the Handheld Dynamometer<\/a> device has been shown to be an excellent tool for this purpose (1,2,24). It is an accurate, reliable and inexpensive technique that can measure hand grip, ankle, elbow, hip, and knee strength. Most of the working groups on sarcopenia recommend assessment of hand grip<\/span> strength, but unfortunately the selected \u201ccutoff\u201d values seem to have wide variation, ranging from 40 and 30 kg for males and females respectively (European Working Group), to 26\/18 kg (Asian Working Group) or even 26\/16 kg (National Institutes of Health) (22). This variation has considerable implications for who may or may not earn the diagnosis of sarcopenia! Furthermore, it could be argued that lower-body strength is much more important for the older individual to maintain independence and functional activity, and we should focus on that rather than grip strength (24). Unfortunately this has not been studied nearly as much at this point, but there has been one validated formula using a simple sit-to-stand test to assess knee extensor strength (25). One important limitation of any strength assessment is variability in patient effort, which can be influenced by things like depression, pain, or cognitive impairment (2,3).<\/p>\n\n\n\n Several tools have been proposed to assess aspects of muscle function\/physical performance<\/span><\/strong> (the other part of criterion #2). A basic gait speed measurement is one of the simplest screening tests for sarcopenia, and has been extensively studied and validated. Most scientific working groups on sarcopenia have agreed on cutoff values of 0.8-1.0 m\/s for gait speed<\/span> testing (1,21,22,24). Another excellent clinical tool is the \u201cShort Physical Performance Battery<\/a>\u201d (SPPB), which includes repeated chair stands, balance testing, and a timed 8-foot walk. Scoring ranges from 0 (worst) to 12 (best), and is predictive of risk for mortality, disability, and nursing home admission. These are simple, inexpensive, and easily assessed parameters in the vast majority of patients.<\/p>\n\n\n\n A more recent proposal of note is the SARC-F questionnaire<\/span> (although there are many, many others). The SARC-F is a simple 5-item screening questionnaire asking about strength, assistance with walking, rise from a chair, climbing stairs, and falls to generate a composite score from 0-10. The scoring system has shown high sensitivity and predictive power for adverse events, but, being a screening<\/span> test, is intended for use in older demographics with an already high prevalence of sarcopenia (27). It has been suggested that a composite scoring method taking other risk factors and comorbid diseases (e.g. obesity, cardiovascular, lung, liver, kidney, or autoimmune diseases) into account might be useful as a predictive tool for younger-aged individuals as well, similar to the FRAX tool<\/a> for osteoporosis and hip fracture risk (22,27).<\/p>\n\n\n\n Finally, biomarkers<\/span><\/strong> are widely used in medicine for a range of conditions and diagnoses because they can be very useful for screening, diagnosis, and evaluating responses to treatment using simple blood or urine tests (3,7). The number of biomarkers correlated<\/span><\/em> with sarcopenia is quite large and includes inflammatory markers (CRP, IL6, TNFa), hemoglobin, albumin, urinary creatinine, hormones (serum DHEA-S, testosterone, IGF-1, vitamin D), products of oxidative stress\/damage, and several others. This long list reflects the large number of mechanisms contributing to sarcopenia, many of which we have covered in these articles. Unfortunately<\/em>, as you may have already guessed, none of these are specific to muscle and are easily confounded by other comorbid disease processes, making them fairly useless for our needs in diagnosing and monitoring sarcopenia over time. There have been two promising candidates for more specific biomarkers, although they aren\u2019t quite ready for clinical use yet. Plasma levels of Procollagen type 3 N-terminal Peptide<\/span> (P3NP) serve as a marker of skeletal muscle remodeling; it tends to be decreased in older individuals, and changes in P3NP levels appear to be predictive of changes in muscle mass and strength (3). Another molecule, C-terminal Agrin Fragment<\/span> (CAF), is a fragment normally released into the serum during neuromuscular remodeling; however, excessive cleavage of the molecule is associated with loss of the neuromuscular junction (which, if you\u2019ll recall from our earlier discussion, is a major contributor to sarcopenia!) (3). With some more research, these molecules may end up being useful to measure in the clinical setting; but until then, we are left without many good options in terms of specific biomarkers for sarcopenia.<\/p>\n\n\n\n Below is the suggested diagnostic algorithm proposed by the European Working Group on Sarcopenia in Older People (EWGSOP) (from source 1). Consider what some of it\u2019s limitations might be before next week\u2019s article.<\/p>\n\n\n\n Let\u2019s wrap this article up. To summarize, we\u2019ve discussed:<\/p>\n\n\n\n In the next and final article we\u2019ll tie everything together and discuss practical implications for the most important topic of all, TREATMENT AND PREVENTION of sarcopenia!<\/p>\n\n\n\n Austin Baraki is a 25 year old student just three months away from completing his M.D. degree. He came to the sport of powerlifting after 15 years of experience competing in and coaching competitive swimming through the collegiate level. Since transitioning to powerlifting he has achieved personal best lifts of a 480 lb squat, 365 lb bench press, and has deadlifted 525\u00d74 at 5\u201910\u201d\/185 lbs. He is specializing in Internal Medicine and has a passion for coaching, teaching, preventive medicine, a nice rare steak, and making gainzZz\u2122.<\/em><\/p>\n\n\n\n References<\/b><\/p>\n\n\n\n 1) Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing.<\/a> 2010 Jul;39(4):412-23.<\/p>\n\n\n\n 2) How to assess functional status: a new muscle quality index. J Nutr Health Aging.<\/a> 2012 Jan;16(1):67-77.<\/p>\n\n\n\n 3) Muscle Quality in Aging: a Multi-Dimensional Approach to Muscle Functioning with Applications for Treatment. Sports Med.<\/a> 2015 Feb 6. [Epub ahead of print]<\/p>\n\n\n\n 4) Motoneuron loss is associated with sarcopenia. J Am Med Dir Assoc. 2014 Jun;15(6):435-9.<\/p>\n\n\n\n 5) The Motor Unit Number Index (MUNIX) in sarcopenic patients. Exp Gerontol. 2013 Apr;48(4):381-4.<\/p>\n\n\n\n 6) Interrelationship between muscle strength, motor units, and aging. Exp Gerontol. 2013 Sep;48(9):920-5.<\/p>\n\n\n\n 7) Biomarkers of sarcopenia in clinical trials-recommendations from the International Working Group on Sarcopenia. J Cachexia Sarcopenia Muscle.<\/a> 2012 Sep;3(3):181-90.<\/p>\n\n\n\n 7a) Treating Sarcopenia In Older And Oldest Old. Curr Pharm Des.<\/a> 2015 Jan 30. [Epub ahead of print]<\/p>\n\n\n\n 8) Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc. 12(4): 249\u2013256.<\/p>\n\n\n\n 9) Training-specific muscle architecture adaptation after 5-wk training in athletes. Med Sci Sports Exerc.<\/a> 2003 Dec;35(12):2013-22.<\/p>\n\n\n\n 10) Histochemical and ultrastructural aspects of m. vastus lateralis in sedentary old people (age 65–89 years). Acta Neuropathol.<\/a> 1980;51(2):99-105.<\/p>\n\n\n\n 11) Effect of aging on human muscle architecture. J Appl Physiol (1985).<\/a> 2003 Dec;95(6):2229-34.<\/p>\n\n\n\n 12) Aberrant repair and fibrosis development in skeletal muscle. Skelet Muscle.<\/a> 2011 May 4;1(1):21.<\/p>\n\n\n\n 13) Intramyocellular lipid content in human skeletal muscle. Obesity (Silver Spring).<\/a> 2006 Mar;14(3):357-67.<\/p>\n\n\n\n 14) Muscle ectopic fat deposition contributes to anabolic resistance in obese sarcopenic old rats through eIF2\u03b1 activation. Aging Cell.<\/a> 2014 Dec;13(6):1001-11.<\/p>\n\n\n\n 15) Increased intramuscular lipid storage in the insulin-resistant and endurance-trained state. Pflugers Arch.<\/a> 2006 Feb;451(5):606-16.<\/p>\n\n\n\n 16) Mitochondrial aging and age-related dysfunction of mitochondria. Biomed Res Int. 2014;2014:238463. By Austin Baraki Recall from our prior articles that a decline in skeletal muscle mass is just one criterion for sarcopenia; in addition, there must also be a loss of strength or physical performance (1). This second criterion was added because the relationship between muscle cross-sectional area (i.e. size) and force production (i.e. strength) is […]<\/p>\n","protected":false},"author":3,"featured_media":1553,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"inline_featured_image":false,"footnotes":""},"categories":[60],"tags":[269,111,53,220,245,128,273,125,268,185,274],"yoast_head":"\n\n
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17) Alterations in intrinsic mitochondrial function with aging are fiber type-specific and do not explain differential atrophy between muscles. Aging Cell. 2011 Dec;10(6):1047-55.
18) Accumulation of severely atrophic myofibers marks the acceleration of sarcopenia in slow and fast twitch muscles. Exp Gerontol. 2011 Aug;46(8):660-9.
19) Increased muscle blood supply and transendothelial nutrient and insulin transport induced by food intake and exercise: Effect of obesity and ageing. J Physiol.<\/a> 2015 Jan 27.
20) Histochemical and ultrastructural aspects of m. vastus lateralis in sedentary old people (age 65–89 years). Acta Neuropathol.<\/a> 1980;51(2):99-105.
21) Sarcopenia: there is a need for some steps forward. J Am Med Dir Assoc.<\/a> 2014 Jun;15(6):379-80.
22) Prevalence, incidence, and clinical impact of sarcopenia: facts, numbers, and epidemiology-update 2014. J Cachexia Sarcopenia Muscle.<\/a> 2014 Dec;5(4):253-9.
23) Defining sarcopenia: the impact of different diagnostic criteria on the prevalence of sarcopenia in a large middle aged cohort. Age (Dordr).<\/a> 2013 Jun;35(3):871-81.
24) Validity and reliability of tools to measure muscle mass, strength, and physical performance in community-dwelling older people: a systematic review. J Am Med Dir Assoc.<\/a> 2013 Mar;14(3):170-8.
25) Sit-to-stand test to evaluate knee extensor muscle size and strength in the elderly: a novel approach. J Physiol Anthropol.<\/a> 2009;28(3):123-8.
26) Validating the SARC-F: a suitable community screening tool for sarcopenia? J Am Med Dir Assoc.<\/a> 2014 Sep;15(9):630-4.
27) SARC-F: a simple questionnaire to rapidly diagnose sarcopenia. J Am Med Dir Assoc.<\/a> 2013 Aug;14(8):531-2.<\/p>\n","protected":false},"excerpt":{"rendered":"