All the individuals underwent at least one single-fre- quency BIA measurement (average of two measure- ments). The measurement was performed on the right side of the body using 800- A and 50-kHz alternating sinusoidal current and a standard tetrapolar technique (BIA 101 Impedance Analyzer, AKERN, Florence, Italy). BIA was performed under standardised condi- tions: a quiet environment, an ambient temperature of 22 C – 24 C and after resting in the supine position for 20 min. After the electrode sites were cleaned with iso- propyl alcohol, electrode patches using a self-adhesive conducting gel (Kendal Care, Resting ECG Electrode, TYCO Healthcare Group LP, Mansfield, MA, USA) were attached. The electrodes were placed proximal to the metacarpal-phalangeal joints in the middle of the dorsal side of the right hand, and just below the trans- verse (metatarsal) arch on the superior side of the right foot. The whole-body impedance vector components, resistance (R) and reactance (Xc), were measured at the same time. Fat mass and skeletalmusclemass were determined using BODYGRAM-Software (AKERN S.r.I. Bioresearch, Florence, Italy).
investigated the change of relative skeletalmuscle over time. In terms of change in relative musclemass over 1 year, a change of SMI between baseline and year 1 could be easily assessed as a percent change by subtract- ing baseline SMI from SMI at year 1. From a practical perspective, using SMI may be a simple and convenient approach with which laypersons are able to easily assess change in their body composition. In a similar context, several studies have reported an annual loss of approxi- mately 1–2% of lean musclemass after about age 50 [39– 42]. In the present study, as a continuous variable, there was a significant decreased risk of metabolic syndrome by 11% per percent increase in SMI over a year, after adjusting for baseline SMI and glycometabolic param- eters. In line with this, a SMI change 0–1 or > 1% over 1 year versus < 0% may have the clinical implication sug- gesting that an increase in relative skeletalmusclemass is a potent preventive parameter for metabolic syndrome. However, there might be concerns regarding dependence of body weight on SMI when SMI changes. Therefore, we analyzed the change of body composition and glyco- metabolic parameters between baseline and year 1 after the adjustment for their corresponding values and found that people having an increase in SMI over a year tended to have decreased body weight and increased ASM over a year. Also, a change in SMI was negatively related with body weight, while positively related with ASM. Moreo- ver, we additionally adopted another ASM/BMI index, which was well correlated with cardiometabolic risk fac- tors than when using ASM/ht 2 , for assessing relative
months of denture wear . It has also been shown that the MMT significantly increases with dental implant therapy . Another study reported an increase in MMT after correction of the occlusal relationship through ortho- dontic treatment in teenagers . However, these studies were not limited to elderly individuals, and they did not investigate the effect of appendicular skeletalmusclemass and muscle strength. Therefore, to date, it is unknown whether occlusal recovery is effective in increasing MMT and pathologically reduced skeletalmusclemass and muscle strength in elderly patients with sarcopenia.
Skeletalmusclemass is regulated by a number of signaling pathways. For example, the activation of the Akt/mTOR signaling pathway induces skeletalmuscle growth (6, 7) and prevents muscle protein degradation (6–9). While promoting mitochondrial biogenesis and metabolic adaptation, activation of AMPK inhibits protein synthesis in skeletalmuscle through suppressing mTOR activity (10, 11). AMPK also induces pro- tein degradation through stimulating the ubiquitin-proteasome system (UPS) and autophagy (12–14). Several inflammatory cytokines, microbial products, and tumor-derived factors induce muscle wasting through the activation of canonical NF-κB and p38 MAPK signaling pathways (15–17). Furthermore, TGF-β and its closely related family members, myostatin, activin, and growth and differentiation factor 11 (GDF11), cause muscle wasting through the activation of Smad2/3 transcription factors (2, 18). However, the proximal signal- ing events that regulate the activation of these pathways in skeletalmuscle remain less understood.
studies indicate that losses of musclemass, protein and fiber size are typically small during hibernation. Furthermore, the ratio of skeletalmusclemass to body mass is maintained (James et al., 2013; Van Dyke et al., 2007; Yacoe, 1983a) or even improved (Hindle et al., 2014; Yang et al., 2014) following hibernation. Interestingly, animals may emerge from hibernation with greater functional capacity in regards to locomotor performance due to the much greater loss of adipose tissue in relation to skeletalmuscle changes. Hibernators also prevent alterations to muscle fiber type ratio that typically accompany inactivity. Most disuse atrophy models show a profound change towards a greater proportion of fast glycolytic muscle fibers. However, a number of studies on hibernators have shown only a marginal loss of oxidative type I fibers and a retention of fiber ratio throughout the winter (Agostini et al., 1991; Cotton and Harlow, 2010; Deveci and Egginton, 2002a; Nowell et al., 2011; Rourke et al., 2004a; Tinker et al., 1998). Perhaps more surprising are the number of studies showing a moderate increase in type I slow oxidative fiber ratio during the hibernation season despite animals spending 90% of the winter season in an essentially immobile state (Agostini et al., 1991; Gao et al., 2012; Hershey et al., 2008; Lazareva et al., 2012; Malatesta et al., 2009; Nowell et al., 2011; Rourke et al., 2006, 2004a). In fact, hibernators on average increase type I fiber ratio by 25% relative to fiber ratios during the summer active period (Table 1).
Recombinant adeno-associated virus (AAV) vectors, owing to their exceptional safety and efficacy profile, are frequently used for in vitro and in vivo gene delivery appli- cations . AAV vectors transduce both dividing and non-dividing cells, and vector genomes are predominantly converted into extrachromosomal episomal DNA in the nucleus . Transgene persistence in transduced terminal postmitotic cells is long-lasting, on the span of years [24 – 26]. We previously observed that AAV vector- mediated systemic delivery of the GDF11 propeptide-Fc (GDF11PRO-Fc) transgene into neonatal mice augmented skeletalmuscle growth . From these findings, we sought to further investigate the impact of both local and systemic GDF11PRO-Fc expression on skeletalmusclemass and function in adult mice and determine whether these effects have therapeutic relevance in the mdx mouse model of Duchenne muscular dystrophy (DMD). In the present study, we find that GDF11PRO-Fc induces skeletalmuscle hypertrophy after gene delivery in adult mice. Furthermore, we observe that systemic GDF11PRO-Fc gene delivery improves muscle strength and reduces intramuscular fibro- sis in mdx mice; however, GDF11PRO-Fc does not improve the dystrophic pathology overall.
The metabolic equivalent (MET) is a widely used physiological concept for quantifying levels of habitual physical activity and cardiorespiratory fitness (CRF) by conveying oxygen consumption requirements of physical activities as multiples of resting or basal metabolic rate (RMR). It may also be used as a means of prescribing workload for exercise training in patient groups, including those attending cardiac rehabilitation (CR). One MET is considered equivalent to the oxygen consumed per kg of body mass at rest 1 (whilst sitting) and, due to practical issues with direct metabolic cart measurement, it is conventionally approximated as 3.5 ml∙kg –1 ∙min –1 . This expression of resting energy expenditure has been incorporated within physical activity position statements and guidelines. 2,3 However, a number of factors including age, gender, body mass (fat-free mass), cardio- metabolic health, and CRF influence RMR, 4 which might limit the broad applicability of the conventional 1 MET at a population level. Widely prescribed cardiac medications, namely beta blockers, have also been cited to influence RMR with some inconsistent findings in males. 5 We aimed to evaluate the potential limitations of using the estimated MET in a cohort of patients with coronary heart disease (CHD), in which we recently reported a positive association between skeletalmusclemass and peak oxygen uptake (V̇O 2 peak). 6 We hypothesised that patients with lower skeletal
As suggested in this study, a lower SVR level was linked with a higher prevalence of NAFLD than that in the higher SVR group, regardless of gender. More- over, SVR would not be related to hepatic steatosis in men. Newman et al. argued that women were associ- ated with a lower musclemass while higher visceral fat than men, so they are more likely to develop func- tional limitations as well as disability related to sarco- penic obesity (including NAFLD), which is consistent with our finding [10, 23]. Otherwise, 90.1% of our Table 2 Correlation analysis between SVR levels and other
prognostic factors in cancers. Sarcopenia is defined as the progressive loss of muscle related to aging or disease . Sarcopenia has been associated with worse outcomes in many types of cancers such as hepatocellular carcin- oma, colorectal cancer, and small cell lung cancer [7 – 9]. For esophageal and gastroesophageal junction cancers, there are conflicting reports. Worse long-term outcomes have been reported in resected esophageal or gastro- esophageal junctional cancers [10 – 12]. Sarcopenia has been linked to increased pulmonary and other complica- tion rates [13, 14]. Decreased skeletalmuscle area during neoadjuvant therapy has also been associated with poorer outcomes and risk of positive clinical resection margin [15, 16]. There are also reports of sarcopenia not being an independent prognostic risk factor for mortal- ity, morbidity, or poor outcomes in EC after neoadjuvant chemoradiotherapy or chemotherapy [14, 17 – 19]. One
Significant differences found between men and women for all SMM parameters of whole body, torso, and UE (and also lower extremity, results not reported) highlighted this principal gender-related characteristic. While there is a reasonable body of data on whole-body parameters, data on UE and torso SMM are very limited. Our results on both whole body and segmental parameters are consistent with existing literature. 3,5,8,9,29 supporting the applicability of BIA for estimating SM parameters in various fields of research on human body composition as well as its relation to muscle function and physical performances (e.g. metabolic diseases associated with muscle wasting, ageing and sarcopenia, sports performance and training-induced changes, muscle rehabilitation and conditioning). Reviewing the literature, we were not able to find any comparable SMI data for the UE.
The afternoon before the start of the race, anthropometric characteristics such as body mass, body height, limb circum- ference, and skinfold thickness at the pectoral, mid axillary, triceps, subscapular, abdominal, suprailiac, front thigh, and medial calf sites were measured. Limb circumference and skinfold thickness were measured on the right side of the body. Using these data, body mass index, percent body fat, and skeletalmusclemass were calculated by anthropomet- ric methods. Body mass was measured using a commercial scale (Beurer BF 15, Beurer, Ulm, Germany) to the nearest 0.1 kg. Body height was determined using a stadiometer to
mass in obese individuals  and a negative association between vitamin D and waist circumference in women with PCOS . Furthermore, vitamin D remains posi- tively associated with skeletalmusclemass after adjust- ing for body fat mass in obese individuals . A large proportion of the women with PCOS had low vitamin D levels (Table 2); however, this is typical of young Canad- ian women because of the limited sun exposure due to northern latitude. The proportion of women with PCOS with vitamin D level lower than 50 nmol/L in our study (41%) is identical to that of Canadians in the same age group from the general population .
between the decrease of the lower leg volume and the estimated skeletalmusclemass, but that this correlation was influenced due to a non-quantified change in tissue fluid in the lower leg. As we were using plethysmogra- phy for measuring the volumes of the whole limbs, we were not able to differentiate a change in volume be- tween arm and hand or between lower leg and foot, re- spectively. This could have influenced our results. Lund-Johansen et al.  measured the displaced water by weighing, which is a similar method to the plethys- mography. These authors concluded that water displace- ment volumetry was a sensitive method for the measurement of leg volume. We therefore think that using plethysmography for measuring the leg volume is a sensitive method as well. Unfortunately, both methods have the limitation of not being able to differentiate be- tween volume changes in the measured compartment or to differentiate between the volume changes of the body composition. For example, if the volume of the lower leg decreases due to a depletion of intramyocellu- lar stored energy while the same amount of volume increases due to oedemata occurring in the skeletalmusclemass or in the adipose subcutaneous tissue, we could not measure any volume change using plethysmo- graphy. In previous studies, it was shown that oedemata did not develop immediately with the exercise or the race but shortly afterwards. Knechtle et al.  measured the highest total body water one day after a Triple Iron ultra-triathlon, Williams et al.  described a peak water retention on day 5 of consecutive hill-walking and Milledge et al.  measured the largest gain in the leg volumes one day after five consecutive days of hill-walk- ing. There is inactive time between exercise bouts, no muscle pump, and therefore the possibility for swelling to build. Nor is there any mechanism to decrease swel- ling on subsequent days.
first group performed resistance training throughout the entire 5 years (Trained), while the other group stopped after 2 years (Detrained). Both groups trained at 80% of their own 1 RM. The two groups significantly improved muscle strength at the end of two years. However, at the 5 year follow-up the Detrained group lost strength compared to the two-year checkpoint. Interestingly however, the overall strength in this Detrained group was still 15.6% higher compared to baseline. Thus, doing something over the two year period was clearly better than doing nothing. Clinicians should confidently rec- ommend that staying physically active can help mitigate the loss in skeletalmusclemass associated with aging.
Dual energy X-ray absorptiometry is the most widespread technique for measuring body composition. 27 DXA uses two different energy spectra to differentiate two materials: either bone or soft tissue, which is the basis for the measurement of bone mineral density (BMD) and content or lean soft tissue mass and fat mass in locations where bone is absent. Taken together, DXA provides an estimate of three body compart- ments, that is, lean, bone, and fat. At bone locations, lean and soft tissue are interpolated from the surroundings. These measurements can be performed for the whole body and for several regions (e.g. trunk, arms, and legs). 28,29 The principle of using DXA for measurement of body composition is based on the notion that when a beam of X-rays is passed through a complex material, the beam is attenuated in proportion to the composition and thickness of the material. The use of two different energy spectra is the basis to separately quan- tify the amount of bone mineral and soft tissue or of fat and lean mass. Lean soft tissue and adipose tissue are mostly comprised by water and organic compounds, which restrict the ﬂ ux of X-rays less than bone. 15,30 DXA is able to assess to- tal body lean soft tissue mass (which includes skeletalmusclemass as well as the mass of all other organs) and appendicu- lar lean soft tissue mass (i.e. an estimate of the musclemass contained in the limbs, which represents about 75% total body skeletalmusclemass). 27
We recently demonstrated induction of an ISR gene program in skeletalmuscle of pigs treated with a beta-adrenergic agonist (BA) , a potent class of muscle anabolic drug. Specifi- cally, treatment with a BA triggered a co-ordinated and temporal increase in expression of 20 + genes that are known transcriptional targets of ATF4, the best-characterized central effector of the ISR gene program. The majority of these genes were involved in amino acid biosynthesis (Phgdh, Psat1, Psph, Pck2, Asns, Arg2, Ass1, Gpt2), tRNA charging (Sars, Tars, Gars, Wars, Iars, Aars), and amino acid transport (Slc3a2, Slc7a1, Slc5a1), as well as inhibition of cellular growth (Sesn2 and Cdkn1a). Importantly, expression of these BA-inducible genes peaked 3 days fol- lowing the initiation of treatment, and declined thereafter. Several other studies have revealed an ISR in skeletalmuscle of rodents and humans following exercise [10,11], inactivity [12,13] and hypertrophic growth [14,15]. However, the role and cause of an ISR during skeletalmuscle growth remains unknown. It is possible that an increased demand for amino acids (caused by increased protein synthesis) triggers an ISR. Alternatively, an ISR could occur due to an accu- mulation of miss-folded proteins, i.e. endoplasmic reticulum (ER) stress, caused by over- reaching the protein synthetic capacity of the cell. Although the precise role of the ER in the maintenance of skeletalmusclemass is unknown, ER-stress (induced by treatment with thap- sigargin) causes anabolic resistance in cultured muscle cells through blockade of mTOR-medi- ated protein translation, exemplifying a link between ER homeostasis and protein metabolism in muscle cells .
high prevalence of polypharmacia, multimorbidity and difficulties in ADL’s characterize the study population as geriatric. Measurement of musclemass by BIA was highly correlated to DXA indicating that BIA is able to identify differences in skeletalmusclemass between geriatric inpatients. However, in absolute terms, BIA sig- nificantly overestimated musclemass. These results are in line with previous findings. Bosaeus et al.  investi- gated several BIA equations and their correlation to DXA measurement of musclemass in 117 hospitalized elderly patients. He found correlation coefficients up to 0.969, depending on the formula used. The slightly higher correlation may be explained by the elimination of outliers, the greater sample size and the lower age of the study participants, as shifts in water homoeostasis tend to increase with age. Again in line with our results, in the same study BIA also significantly overestimated Table 3 Accuracy of BIA in reference to DXA in identifying patients with reduced musclemass (a) and sarcopenia (b)
To the best of our knowledge, no study has previously addressed the association between the risk of malnutri- tion at admission and change of muscle strength or musclemass during hospitalization. We did expect to find a decrease of musclemass during hospitalization due to the high prevalence of inactivity and malnutrition in older patient populations. A balance between anabolic and catabolic processes is required to maintain skeletalmusclemass . Evidence shows that malnutrition can lead to a negative skeletalmuscle protein balance, fol- lowing muscle loss . Theoretically, a week of physical inactivity increases skeletalmuscle catabolism and decreases anabolism . Notwithstanding, we did not find a significant decrease of skeletalmuscle-, fat free mass and skeletalmuscle index in the low-risk or the high-risk group. This was in line with a previous study in which no statistically significant change of fat free mass (measured by BIA) during hospitalization was found in 23 COPD patients with a mean age of 63 years . In another study, a significant decrease of lean body mass was found after seven days of hospital stay in a group of 20 patients who had a median age of 70 years and underwent colorectal surgery . This result may be due to low appetite, vomiting and disturbed gastro- intestinal function after abdominal surgery in this se- lected patient population. Our study design minimized the risk of selection bias and the variety in specialisms ensured heterogeneity and a good representation of daily clinical practice.
However, previous studies have shown that the Chinese population, like other Asian populations, has a lower BMI but a higher percentage of body fat than Caucasians of similar age and gender. 29 BMI does not differentiate between bone, mus- cle, and fat mass, so a simple and inexpensive method of assessing fat mass may be better for predicting the develop- ment of GDM. Methods such as bioelectrical impedance ana- lysis for the assessment of fat mass and fat-free mass in pregnant women in the body composition studies have been described. 30 – 35 Our study establishes that BIA is a feasible and reproducible method that can be used during pregnancy. We found pregnant women with FMP over 28% had a higher risk of developing GDM than women with normal FMP (adjusted OR 1.572, 95% CI 1.104 – 2.240). These results are similar to those of previous studies, in which the visceral fat mass, 12 thickness of subcutaneous adipose tissue, 15 and body fat index (thickness of pre-peritoneal fat (mm) × thickness of subcutaneous fat (mm)/height (cm)) were good markers for determining the risk of the development of GDM. 17 We also found that SMMP was negatively correlated with increased risk of gestational diabetes. According to a study conducted by Kawanabe et al, inadequate appendicular skeletalmusclemass/fat mass ratio is a risk for the development of insulin resistance in Japanese patients with GDM. 29 Unfortunately, we did not evaluate the relationship between SMMP and insulin resistance since insulin test is not included in the routine