J Cachexia Sarcopenia Muscle (2012) 3:181–190 183 , sen .su l , rs liiitlilrscacecaaenhdn60yw ,,ltttttitrrsseaaechohhngon ,iilrrsssseeaeaeecpphdum ttlititititiracecaenduonhwm tilrrrsssseeeaeydodovunhm tlttii(--rsaecanku6gnwm ./tti-(-sseea104o6dp<mm tlrrsseehodno liifsacunyhnp iilfscceecpudxE ilrssseaeacaduv iltrreaaecndppn ieaccaaxhnd ltiseaceakdudnw t:ir)og004npom tlt)recaghnk P D s n o i t i n i f e d a i n e p o c r a s s u s n e s n o c f o y r a m m u S 1 e l b a T ] 9 [ y t i l i b o m d e t i m i l h t i w a i n e p o c r a S n i a i x e r o n a – a i exh ]1 ac [1 c s : e p s a u e ro is tG dg tlrsn tisw e n e a I ia ic c n epS rcho n i a i n e p o c r a S n o p u o r G ing ]0 rk [1 aonW leepo ep rP o e ruE ldO ] 8 [ e c r o F k s a T a i n e p o c r a S A N A I p u o r G s n o s r e p r e d l O r e d l o d n a s r a e y 5 6 d e g a s n o s r e p l l A isen ,ro lien tehn c g ld trs ac , iin ino l t ithw c lfacun tsu a t tjseub icyph lseahh c s t S - a taeg lpopu tion r T ssanm rsaey ea an 30 l r em 02– a l aecppu leebohw rssaeenodg ir)cgoup id t n llspuow itisavno lthpy teehn ng ed eah sam itifcunno trsaandd ireund treohm roo ≥(2 seam lfod P w em tiag tiaG lac lo a tiiseaebnov ttlfssehou llssauuow .tti)segnk itrseyhph d ad lu la o rad ng )p w yb an oy ndu -4m cead .s d u ≥t(sssa2m irsaeenud irccagkob t/isenh lreepb rseaeu ce nm teh .8m can cem n l 0 ts an sum aem and (ed< teed fr m o ow teh sex sep sp e ep r L treceodo tiseepd ;tilfhow tseepd w ,/sp fIag tregn dy itagh ltubo .08m .iton irspg tobdo tisnw seepd ≤ed laavu and cee ion tiae ita tisaep iiteon rsaeuh ,trhgpo ltaeavu issanp lraogm th .Ifeedg scopom ,/semm tlrsecen tiisonpo lsecum /rsonm tlrseecng tsap odyb .08> sum com owm ≤.08 sum i G L .)d tod ee e itsp rceo tion a agm ,/sp l u a - m ev (4 .0 n iton 1< itiso cn eed op fau itsp com l c a y i hy Ifg bdo s P g n i n e e r c S 7 io ssa red .56 t m au ≤,n ra an sq e low lrea adn inm lpu s icdu l ) 2 inng eppn byDXA ./27k3gm )eonwm tio a nu een ssed ≤t(h 2 in c rf oo t ebw (ssae g ieh /m kg P e itn o itrav iifn ep ed O over time, and help clinical and therapeutic decision- making processes. Taking this definition into account, the functional, biological, or imaging-related parameters con- sidered in the present document will be hereby generally referred to with the term “biomarker.” There are currently numerous parameters that are poten- tially able to track the age-related skeletal muscle decline. Depending on the parameter chosen to define sarcopenia, different information might be obtained. Such variability depends on the specific characteristics of each parameter and the mechanisms measured by the parameter. The intrin- sic (e.g., accuracy, specificity, sensitivity) and extrinsic (e.g., cost, availability, time to be performed) properties of each biomarker will largely drive its use in research trials, making it more suitable for screening, baseline evaluation, and/or definition of outcomes (Table 2). The use of biomarkers in a given study must be “fit for purpose.” Thus, several different biomarkers may be re- quired to support different aspects of the development of a therapeutic intervention. For example, biomarkers for detec- tion and diagnosis may not be the same as those that ideally track disease progression. Likewise, for new therapeutic agents, a single assay may not suffice as a biomarker reflect- ing both target engagement and the pharmacodynamic effects of a drug. 4 Muscle quantity versus muscle quality Although muscle mass can objectively define the presence of sarcopenia, several components of skeletal muscle func- tion are not adequately captured by simply measuring mass or cross-sectional area. It is now clear that there is a certain degree of divergence between changes in muscle mass and alterations in muscle performance. The well-described de- cline in skeletal muscle mass in older adults is a critical determinant of age-related weakness, which is defined as a reduction in maximal voluntary joint torque or power. Yet, it is now clear that the relationship between force production capability and muscle size in older adults is less robust than it is in young people [13]. Indeed, longitudinal studies have demonstrated that the age-related decline in muscle strength far exceeds the observed changes in muscle mass or size, particularly in weight-stable individuals [14, 15]. Further- more, longitudinal studies indicate that maintenance or even gain of muscle mass may not prevent weakness in older adults [15, 16]. In addition, a number of age-related changes in force production capability are not readily explained by a reduction in muscle mass, including decreased specific force (force per cross sectional area) [17, 18] and slower rate of isometric force production (expressed relative to peak torque or to body weight) [19, 20]. Furthermore, voluntary weight loss leads to reductions in muscle mass/size with no declines