the european working group on sarcopenia in older people   has recently suggested that the definition of sarcopenia should include not only low muscle mass but also low muscle function ( strength or performance ) because sarcopenia is a syndrome that is characterized by both . the loss of muscle mass and strength are problems that plague many older adults , though the causal and correlative link between diminishing lean mass and strength is not well supported in aging humans . aging is also characterized by increasing depots of fat both between and within skeletal muscles . this increase in intramuscular adipose tissue ( imat ) , and its lipotoxic effect , has been identified as a potential contributor to declining strength and muscle quality ; with some also associating it with mobility limitations in older adults [ 48 ] . the recent structural focus on imat content rather than lean muscle mass is important as it could provide a plausible explanation for age - associated strength and mobility deficits . fatty infiltration into skeletal muscle may alter muscle fiber orientation and hence the force producing capabilities of the whole muscle . imat may also be a metabolically active component of muscle that secretes inflammatory cytokines leading to systemic inflammation , much like visceral adipose tissue , that can inhibit muscle force production even in the absence of muscle atrophy . further , imat may be an appropriate therapeutic rehabilitation target as some suggest its presence can blunt the strength response to resistance training . currently , it is accepted that muscle weakness , loss of lean tissue mass , and imat contribute to functional decline . in order to gain insight and parcel out the contributions of these muscle variables to mobility , this study examined the association of imat of the thigh , along with muscle lean tissue and muscle strength , with mobility measures in older adults . one hundred and nine older ( mean = 74.1 years  6.8 ) adults participated in this study . recruitment occurred over a 5-year period from 20062011 and consisted of receiving names and identifying information from clinical databases at the university of utah . each of the subjects received a personal letter providing information about the study , and they were then contacted directly via phone or in - person to assess their interest and to screen for eligibility following receipt of a signed informed consent document . the 109 subjects were community ambulating males ( n = 32 ) and females ( n = 77 ) 60 years of age or older with 2 or more comorbid disease conditions and were at risk for falling due to fatigue , muscle weakness and/or had experienced a fall in the previous 12 months . all scored > 23 on a folstein minimental examination or passed the mini - cog instrument for dementia . individuals were excluded if they had any of the absolute contraindications for mri , progressive diagnosed neurologic disease ( e.g. , parkinson 's , multiple sclerosis , guillain - barre , and alzheimer 's ) , any dystrophies , or rheumatologic conditions that primarily affect muscle ( muscular dystrophy , pmr ) or had been participating in regular ( 3x / week ) aerobic or resistance exercise over the past 12 months ( table 1 ) .   knee extension strength was determined via a maximum voluntary isometric contraction ( mvic ) on a kincom dynamometer ( chattanooga inc . , hixon , tn ) as follows : participants were stabilized by chest and thigh straps and seated with their knees fixed at 60 degrees of flexion with their arms folded across their chest . prior to testing , participants practiced submaximal contractions at 50 and 75% of their perceived maximal effort prior to one practice maximal contraction trial . after a 2-minute rest period , three separate maximal contractions were performed . the outcome variable muscle force was calculated as the average peak force of three trials . the respective imat and lean tissue cross - sectional areas were calculated from the mri scans . subjects were placed supine in a 3.0  tesla whole body mr imager ( siemens trio , siemens medical , erlangen , germany ) . the legs were scanned in a coronal plane with a turbo spin echo ( tse ) t1-weighted sequence to depict the femoral heads and the femoral condyles . the midpoint of the thigh was determined and defined as half way between the superior margin of the femoral head and the inferior margin of the femoral condyles . axial imaging ( 5  mm thick slices at 1  cm intervals ) of the legs was then performed over 1/2 the length of the femur , centered at the midpoint of the thigh . this was performed with a three - point dixon multislice 2d gradient recalled echo ( gre ) sequence ( tr = 300  ms , te = 5.15/6.4/7.65  ms , and matrix size = 512  288 ) . field of view was adjusted to the individual subject anatomy to obtain optimal in - plane spatial resolution , typically 1  1  mm or better . separate fat and water images were created with custom software using the three - point dixon method . a tissue model was then used to calculate estimates of total fat and nonfat volume fractions on a per - pixel basis , which were displayed in image form . four images from the middle 1/3 of each thigh were used to determine average cross - sectional area ( cm ) of imat and lean tissue . manual tracing eliminated subcutaneous fat and bone and isolated the fascial border of the thigh to create a subfascial region of interest ( roi ) . total imat and lean tissue were calculated by summing the value of percent fat fraction and percent lean tissue fraction over all pixels within the roi using custom - written image analysis software ( matlab ; the mathworks , natick , massachusetts ) . this sum was multiplied by the area of each pixel to give total fat and lean tissue csas within the roi . this method accurately measures fat and lean tissue in pixels that contain both   by allowing fractional contributions to the fat and lean tissue csa calculations . this allows microscopic fat within muscle tissue as well as thin planes of fat adjacent to fascial planes to be accurately taken into account , even when image resolution is inadequate to delineate these visually ( figure 1 ) .    the same investigator , blinded to time point of the scan and slice location , performed measurements of individual participants . this technique has demonstrated high levels of intrarater reliability , test - retest reliability [ 13 , 14 ] , and concurrent validity when compared to imaging of a cadaveric phantom limb . mobility was determined using four tests : ( 1 ) a six - minute walk ( 6mw ) , ( 2 ) stair ascent ( stair a ) , ( 3 ) stair descent ( stair d ) , and ( 4 ) a timed up and go ( tug ) . these performance tests were chosen to represent mobility function and have been shown to be both valid and reliable in this population [ 1517 ] . the 6mw test , a measure of the distance a subject walks in 6 minutes , was used to assess overall mobility . participants were asked to cover as much distance as possible in six minutes without running . the stair a test required participants to ascend one flight of stairs under close or contact supervision as quickly and safely as possible . time was recorded to the nearest 0.01 second from a verbal go signal to final foot placement on a standard flight of 10 stairs , and the average of three trials was recorded . the stair d test was performed exactly as the stair a test , except that participants were required to descend one flight of stairs as quickly and safely as possible . the tug test required participants to rise from a seated position , walk out 3 meters , turn around , and return to sitting as quickly and safely as possible . time was recorded to the nearest 0.01 second from the time the person 's buttocks left the chair until return contact with the chair . data management and statistical analyses were performed with pasw statistics 18.0 ( spss , chicago , il ) . descriptive data were calculated for demographic variables and dependent measures and are presented as means  sd . pearson correlation coefficients were calculated to determine the bivariate relationship between each muscle and mobility variable . the relative contribution of each muscle variable to explaining the variability in the mobility outcomes were examined using step - wise hierarchical linear regression models . each mobility test was used as the dependent variable in separate models , with knee extension strength , quadriceps lean tissue , and imat considered for entry in a stepwise manner . for each variable entered in the final model , the part correlation was examined to determine the unique amount of variance in the mobility outcome that was accounted for by the variable . the bivariate correlation of mobility variables with muscle variables revealed moderately strong and significant correlations ( r range = 0.230.55 , p < 0.05 ) ( table 2 ) . the direction of the correlations indicates that as strength and average lean tissue increase , mobility function improves . as average imat increases , mobility function declines . these results support the use of step - wise regression analyses to examine the unique and shared contributions of the muscle variables towards explaining the variance in mobility measures .   the multiple regression analysis on the 6mw revealed that the predictors as a group accounted for 34.6% of the variance in walk distance , with strength ( p = 0.005 ) , imat ( p = 0.002 ) , and lean ( p = 0.005 ) each significantly contributing to the final model ( p = 0.005 ) . the part correlation of strength was 0.23 , of imat was 0.30 , and of lean was 0.23 indicating that strength , imat , and lean explained 5.3% , 9.0% , and 5.3% of the variance in the 6mw score , respectively , with all other variables in the model held constant . the predictor variables as a group accounted for 45.1% of the variance in stair ascent time , with strength ( p = 0.001 ) and imat ( p < 0.001 ) contributing significantly to the final model ( p = 0.001 ) . the part correlation of strength was 0.54 and of imat was 0.39 , indicating that strength and imat explained 29.2% and 15.2% of the variance in the stair ascent scores , respectively , with all other variables in the model held constant . the predictor variables as a group accounted for 37.4% of the variance in stair descent time , with strength ( p = 0.001 ) and imat ( p = 0.001 ) contributing significantly to the final model ( p = 0.001 ) . the part correlation of strength was 0.49 and of imat was 0.37 , indicating that strength explained 24.0% and imat explained 13.7% of the variance in stair descent with all other variables in the model held constant . the predictor variables as a group accounted for 26.5% of the variance in tug score , with strength ( p = 0.001 ) and imat ( p = 0.001 ) contributing significantly to the final model ( p = 0.001 ) . the part correlation of strength was 0.42 and of imat was 0.28 , indicating that strength and imat explained 17.6% and 7.8% of the variance in tug scores , respectively , with all other variables in the model held constant ( table 3 ) . the novel finding in this investigation is that even when accounting for total body mass , thigh muscle adipose tissue surfaces as a potent muscle variable related to the ability of older adults to move about in their community . specifically , normalized muscle strength , imat and lean tissue composition measured via mri were tested to determine the contribution of these muscle variables to declining mobility levels in older adults . the link between imat and mobility deficits has been shown in large epidemiological studies ; however , this is the first study to target older individuals needing mobility related rehabilitation interventions . skeletal muscle lipid content in older men and women is independently associated with maximal torque production even after adjusting for muscle size , height , weight , age , and race , accounting for 3236% of the total variance in strength . greater fat infiltration into muscle is also associated with increased risk of future mobility loss in older men and women . our results punctuate the potential negative impact of fatty infiltration of muscle on mobility function , an important component of sarcopenia in the elderly and are particularly interesting considering that imat explains a surprisingly high amount of the variance in these mobility tasks . though by no means causal , the correlations reported here between imat and specific performance tests of mobility function in older adults support , in part , the potential inflammatory pathway linking ectopic fat deposition and deteriorating physical ability of older individuals . evidence of a direct effect of inflammatory cytokines on muscle catabolism [ 19 , 20 ] , combined with the knowledge that inflammation is often elevated with aging [ 21 , 22 ] suggests inflammation could be a reason for functional decline and frailty . the current study , however , does not provide any data to support this hypothesized role , and the lack of any biochemical data should be considered a limitation . recent evidence [ 23 , 24 ] suggests that an elevated inflammatory milieu is associated with loss of muscle , strength , and function in the older individuals , making it tempting to speculate that a connection between imat , inflammation , and sarcopenia exists , and future interventions should target not only the impact of lean tissue loss , but also of increased imat deposits . there is wide variation in aging populations with respect to mobility levels , comorbid conditions , and body composition . because of this , strong correlations between these variables are difficult to identify . a recent review of body composition factors and their relationship to mobility in older individuals   highlights this fact , emphasizing the importance of our results and suggesting that future studies should examine imat as an important variable with respect to sarcopenia and mobility function in older individuals . future studies are needed to confirm these findings and to determine whether decreases in imat are associated with concurrent improvement in mobility function . additionally , the participants in this study , while varying in age between 60 and 93 years , were generally high - functioning individuals . because individuals functioning at lower levels were not included , this should be considered when generalizing these findings . this newly identified muscle impairment has not traditionally been targeted by clinicians concerned with sarcopenia , but now in addition to the loss of lean tissue and muscle strength , imat should be considered an important factor that may contribute to deficits in mobility in the aging population . preliminary data show that moderate physical activity in older adults may prevent skeletal muscle fat infiltration   and that exercise can decrease imat [ 27 , 28 ] . this suggests that imat may be amenable to change with exercise countermeasures , though these findings are limited by small sample sizes and nonrandomized designs . well controlled , randomized studies are needed to determine the best exercise countermeasure to decrease imat and importantly , how this decrease impacts mobility function in mobility limited older adults . thigh imat contributes a significant amount of variance to the mobility performance of older adults needing rehabilitation , even when accounting for total body mass . imat has a negative impact on mobility function , an important component of sarcopenia in the elderly . locomotor muscle fatty infiltration , in addition to lean tissue and muscle strength , should be considered an important factor contributing to mobility deficits in this vulnerable population .
objective . intramuscular adipose tissue ( imat ) and sarcopenia 
 may adversely impact mobility function and physical activity . 
 this study determined the association of locomotor muscle structure and function with mobility function in older adults . 
 method . 
 109 older adults with a variety of comorbid disease conditions were examined for thigh muscle composition via mri , knee extensor strength via isometric dynamometry , and mobility function . 
 the contribution of strength , quadriceps lean tissue , and imat to explaining the variability in mobility function was examined using multivariate linear regression models . 
 results . 
 the predictors as a group contributed 2745% of the variance in all outcome measures ; however , imat contributed between 815% of the variance in all four mobility variables , while lean explained only 5% variance in only one mobility measure . 
 conclusions . 
 thigh imat , a newly identified muscle impairment appears to be a potent muscle variable related to the ability of older adults to move about in their community .