Expression and Roles of Lynx1, a Modulator of Cholinergic Transmission, in Skeletal Muscles and Neuromuscular Junctions in Mice.

Lynx1 is a glycosylphosphatidylinositol (GPI)-linked protein shown to affect synaptic plasticity through modulation of nicotinic acetylcholine receptor (nAChR) subtypes in the brain. Because of this function and structural similarity to α-bungarotoxin, which binds muscle-specific nAChRs with high affinity, Lynx1 is a promising candidate for modulating nAChRs in skeletal muscles. However, little is known about the expression and roles of Lynx1 in skeletal muscles and neuromuscular junctions (NMJs). Here, we show that Lynx1 is expressed in skeletal muscles, increases during development, and concentrates at NMJs. We also demonstrate that Lynx1 interacts with muscle-specific nAChR subunits. Additionally, we present data indicating that Lynx1 deletion alters the response of skeletal muscles to cholinergic transmission and their contractile properties. Based on these findings, we asked if Lynx1 deletion affects developing and adult NMJs. Loss of Lynx1 had no effect on NMJs at postnatal day 9 (P9) and moderately increased their size at P21. Thus, Lynx1 plays a minor role in the structural development of NMJs. In 7- and 12-month-old mice lacking Lynx1, there is a marked increase in the incidence of NMJs with age- and disease-associated morphological alterations. The loss of Lynx1 also reduced the size of adult muscle fibers. Despite these effects, Lynx1 deletion did not alter the rate of NMJ reinnervation and stability following motor axon injury. These findings suggest that Lynx1 is not required during fast remodeling of the NMJ, as is the case during reformation following crushing of motor axons and development. Instead, these data indicate that the primary role of Lynx1 may be to maintain the structure and function of adult and aging NMJs.

A Novel Egr-1-Agrin Pathway and Potential Implications for Regulation of Synaptic Physiology and Homeostasis at the Neuromuscular Junction.

Synaptic transmission requires intricate coordination of the components involved in processing of incoming signals, formation and stabilization of synaptic machinery, neurotransmission and in all related signaling pathways. Changes to any of these components cause synaptic imbalance and disruption of neuronal circuitry. Extensive studies at the neuromuscular junction (NMJ) have greatly aided in the current understanding of synapses and served to elucidate the underlying physiology as well as associated adaptive and homeostatic processes. The heparan sulfate proteoglycan agrin is a vital component of the NMJ, mediating synaptic formation and maintenance in both brain and muscle, but very little is known about direct control of its expression. Here, we investigated the relationship between agrin and transcription factor early growth response-1 (Egr-1), as Egr-1 regulates the expression of many genes involved in synaptic homeostasis and plasticity. Using chromatin immunoprecipitation (ChIP), cell culture with cell lines derived from brain and muscle, and animal models, we show that Egr-1 binds to the AGRN gene locus and suppresses its expression. When compared with wild type (WT), mice deficient in Egr-1 (Egr-1-/-) display a marked increase in AGRN mRNA and agrin full-length and cleavage fragment protein levels, including the 22 kDa, C-terminal fragment in brain and muscle tissue homogenate. Because agrin is a crucial component of the NMJ, we explored possible physiological implications of the Egr-1-agrin relationship. In the diaphragm, Egr-1-/- mice display increased NMJ motor endplate density, individual area and area of innervation. In addition to increased density, soleus NMJs also display an increase in fragmented and faint endplates in Egr-1-/- vs. WT mice. Moreover, the soleus NMJ electrophysiology of Egr-1-/- mice revealed increased quantal content and motor testing showed decreased movement and limb muscle strength compared with WT. This study provides evidence for the potential involvement of a novel Egr-1-agrin pathway in synaptic homeostatic and compensatory mechanisms at the NMJ. Synaptic homeostasis is greatly affected by the process of aging. These and other data suggest that changes in Egr-1 expression may directly or indirectly promote age-related pathologies.

Muscle strength and force development in high- and low-functioning elderly men: Influence of muscular and neural factors.

BACKGROUND: Aging leads to a loss of muscle strength and functional capacity likely resulting from a combination of neural and muscle alterations. The aim of this study was to identify possible disparities in muscle strength and force development profiles in high- and low-functioning elderly men and to investigate muscular and neurophysiological factors that could explain the differences. METHODS: Sixty community-dwelling men in good general health were divided in two groups based on a functional capacity (FC) z-score derived from 6 tests of the Short Physical Performance Battery and Senior Fitness Test (Normal and fast 4m-walk tests, normal and fast Timed-up and go, chair and stair tests). Extensor strength of the lower limbs (LL) was obtained for concentric (CLES) contraction and combined with lean masses of LL (LLLM) to yield concentric (CLES/LLLM) index. Similarly, extensor strength of the right Quadriceps Femoris (IKES) was obtained during maximal voluntary isometric contraction (MVC) and combined with right thigh lean mass (rTLM) to produce an isometric strength (IKES/rTLM) index. A muscular profile was obtained from: ascending and descending force slopes during the MVC; Vastus Lateralis (VL) muscle twitches parameters (amplitude, contraction and ½ relaxation times); the knee joint velocity (KV) as well as integrated EMG (iEMG) were determined for a sit-to-stand functional evaluation; muscle phenotype. A neurophysiological profile was established from: the spinal excitability (Hmax/Mmax ratio); motoneuron conduction velocity (CV); the completeness of muscle activation (% of force reserve), median power frequency (MPF) and mean amplitude (MA) of the VL EMG signal during MVC. RESULTS: Coincidently, age did not differ between groups. Strength and force indices, descending force slopes for MVC, KV and iEMG during the sit-to-stand evaluation and FC parameters were all significantly (p<0.05) lower in the LoFC group than in the HiFC group. In contrast, no difference was observed between groups in: LLLM and rTLM, Hmax/Mmax ratio, CV, twitch parameters and muscle phenotype. CONCLUSION: The lower concentric and isometric strengths found in the LoFC group could not be accounted for by muscular factors. Similarly, peripheral nervous systems alterations could not explain group differences. It can be suggested that modifications within the central nervous system may be responsible for the differences in the functional status of healthy elderly individuals. Finally, more complex and demanding tasks, such as those requiring greater intensity or coordination, may further clarify how healthy elderly individuals with low and high functional capacities differ.

Mitochondrial energy deficiency leads to hyperproliferation of skeletal muscle mitochondria and enhanced insulin sensitivity.

Diabetes is associated with impaired glucose metabolism in the presence of excess insulin. Glucose and fatty acids provide reducing equivalents to mitochondria to generate energy, and studies have reported mitochondrial dysfunction in type II diabetes patients. If mitochondrial dysfunction can cause diabetes, then we hypothesized that increased mitochondrial metabolism should render animals resistant to diabetes. This was confirmed in mice in which the heart-muscle-brain adenine nucleotide translocator isoform 1 (ANT1) was inactivated. ANT1-deficient animals are insulin-hypersensitive, glucose-tolerant, and resistant to high fat diet (HFD)-induced toxicity. In ANT1-deficient skeletal muscle, mitochondrial gene expression is induced in association with the hyperproliferation of mitochondria. The ANT1-deficient muscle mitochondria produce excess reactive oxygen species (ROS) and are partially uncoupled. Hence, the muscle respiration under nonphosphorylating conditions is increased. Muscle transcriptome analysis revealed the induction of mitochondrial biogenesis, down-regulation of diabetes-related genes, and increased expression of the genes encoding the myokines FGF21 and GDF15. However, FGF21 was not elevated in serum, and FGF21 and UCP1 mRNAs were not induced in liver or brown adipose tissue (BAT). Hence, increased oxidation of dietary-reducing equivalents by elevated muscle mitochondrial respiration appears to be the mechanism by which ANT1-deficient mice prevent diabetes, demonstrating that the rate of mitochondrial oxidation of calories is important in the etiology of metabolic disease.

The impact of ageing, physical activity, and pre-frailty on skeletal muscle phenotype, mitochondrial content, and intramyocellular lipids in men.

BACKGROUND: The exact impact of ageing on skeletal muscle phenotype and mitochondrial and lipid content remains controversial, probably because physical activity, which greatly influences muscle physiology, is rarely accounted for. The present study was therefore designed to investigate the effects of ageing, physical activity, and pre-frailty on skeletal muscle phenotype, and mitochondrial and intramyocellular lipid content in men. METHODS: Recreationally active young adult (20-30 yo; YA); active (ACT) and sedentary (SED) middle-age (50-65 yo; MA-ACT and MA-SED); and older (65 + yo; 65 + ACT and 65 + SED) and pre-frail older (65 + PF) men were recruited. Muscle biopsies from the vastus lateralis were collected to assess, on muscle cross sections, muscle phenotype (using myosin heavy chain isoforms immunolabelling), the fibre type-specific content of mitochondria (by quantifying the succinate dehydrogenase stain intensity), and the fibre type-specific lipid content (by quantifying the Oil Red O stain intensity). RESULTS: Only 65 + SED and 65 + PF displayed significantly lower overall and type IIa fibre sizes vs. YA. 65 + SED displayed a lower type IIa fibre proportion vs. YA. MA-SED and 65 + SED displayed a higher hybrid type IIa/IIx fibre proportion vs. YA. Sedentary and pre-frail, but not active, men displayed lower mitochondrial content irrespective of fibre type vs. YA. 65 + SED, but not 65 + ACT, displayed a higher lipid content in type I fibres vs. YA. Finally, mitochondrial content, but not lipid content, was positively correlated with indices of muscle function, functional capacity, and insulin sensitivity across all subjects. CONCLUSIONS: Taken altogether, our results indicate that ageing in sedentary men is associated with (i) complex changes in muscle phenotype preferentially affecting type IIa fibres; (ii) a decline in mitochondrial content affecting all fibre types; and (iii) an increase in lipid content in type I fibres. They also indicate that physical activity partially protects from the effects of ageing on muscle phenotype, mitochondrial content, and lipid accumulation. No skeletal specific muscle phenotype of pre-frailty was observed.

Is handgrip strength normalized to body weight a useful tool to identify dynapenia and functional incapacity in post-menopausal women?

ABSTRACT Objective To investigate whether handgrip strength normalized to body weight could be a useful clinical tool to identify dynapenia and assess functional capacity in post-menopausal women. Method A total of 136 postmenopausal women were recruited. Body composition (Dual Energy X-ray Absorptiometry [DEXA], Bio-electrical Impedence Analysis [BIA]), grip strength (dynamometer) and functional capacity (senior fitness tests) were evaluated. Dynapenia was established according to a handgrip strength index (handgrip strength divided by body weight (BW) in Kg/KgBW) obtained from a reference population of young women: Type I dynapenic (<0.44 kg/KgBW) and type II dynapenic (<0.35 kg/KgBW). Results The results show a positive correlation between handgrip strength index (in kg/KgBW) and alternate-step test (r=0.30, p<0.001), chair-stand test (r=0.25, p<0.005) and one-leg stance test (r=0.335, p<0.001). The results also showed a significant difference in non-dynapenic compared to type I dynapenic and type II dynapenic for the chair-stand test (Non-dynapenic: 12.0±3.0; Type I: 11.7±2.5; Type II: 10.3±3.0) (p=0.037 and p=0.005, respectively) and the one-leg stance test (Non-dynapenic: 54.2±14.2; Type I: 43.8±21.4; Type II: 35.0±21.8) (p=0.030 and p=0.004, respectively). Finally, a significant difference was observed between type II dynapenic and non-dynapenic for the chair-stand test (p=0.032), but not with type I dynapenic. Conclusion The results showed that handgrip strength was positively correlated with functional capacity. In addition, non-dynapenic women displayed a better functional status when compared to type I and type II dynapenic women. Thus, the determination of the handgrip strength thresholds could be an accessible and affordable clinical tool to identify people at risk of autonomy loss.

Is handgrip strength normalized to body weight a useful tool to identify dynapenia and functional incapacity in post-menopausal women?

Objective: To investigate whether handgrip strength normalized to body weight could be a useful clinical tool to identify dynapenia and assess functional capacity in post-menopausal women. Method: A total of 136 postmenopausal women were recruited. Body composition (Dual Energy X-ray Absorptiometry [DEXA], Bio-electrical Impedence Analysis [BIA]), grip strength (dynamometer) and functional capacity (senior fitness tests) were evaluated. Dynapenia was established according to a handgrip strength index (handgrip strength divided by body weight (BW) in Kg/KgBW) obtained from a reference population of young women: Type I dynapenic (<0.44 kg/KgBW) and type II dynapenic (<0.35 kg/KgBW). Results: The results show a positive correlation between handgrip strength index (in kg/KgBW) and alternate-step test (r=0.30, p<0.001), chair-stand test (r=0.25, p<0.005) and one-leg stance test (r=0.335, p<0.001). The results also showed a significant difference in non-dynapenic compared to type I dynapenic and type II dynapenic for the chair-stand test (Non-dynapenic: 12.0±3.0; Type I: 11.7±2.5; Type II: 10.3±3.0) (p=0.037 and p=0.005, respectively) and the one-leg stance test (Non-dynapenic: 54.2±14.2; Type I: 43.8±21.4; Type II: 35.0±21.8) (p=0.030 and p=0.004, respectively). Finally, a significant difference was observed between type II dynapenic and non-dynapenic for the chair-stand test (p=0.032), but not with type I dynapenic. Conclusion: The results showed that handgrip strength was positively correlated with functional capacity. In addition, non-dynapenic women displayed a better functional status when compared to type I and type II dynapenic women. Thus, the determination of the handgrip strength thresholds could be an accessible and affordable clinical tool to identify people at risk of autonomy loss.

Muscle Strength and Body Weight Mediate the Relationship Between Physical Activity and Usual Gait Speed.

BACKGROUND: Usual gait speed (UGS) is recognized as a good indicator of a variety of health conditions as well as a predictor of future disability and mortality. There is evidence that UGS increases with physical activity. Muscle function and body composition changes may mediate these changes. However, we do not know exactly which of these factors contribute to the effect of physical activity on gait speed or the magnitude of their contribution. METHODS: Data are from 1378 women aged 75 years and older recruited in the Toulouse EPIDémiologie de l'OStéoporose cohort. Body weight and composition (dual energy X-ray absorptiometry), knee extension strength, and physical activity habits were assessed. The INDIRECT macro for SPSS (SPSS Inc, Chicago, IL) was used to determine total and specific indirect effects of physical activity on UGS through body weight (BW) and composition as well as muscle mass and strength. RESULTS: Knee extension strength [95% confidence interval (CI) 0.0091, 0.0231] and BW (95% CI 0.0037, 0.0412), but not fat mass or muscle mass, were mediators of the relationship between physical activity and gait speed. However, muscle mass significantly mediated the relationship between physical activity and muscle strength (95% CI -3.0722, -0.6265). CONCLUSIONS: Results suggest that muscle strength and BW are the most significant mediators of the relationship between physical activity and UGS. Although the specific effect of muscle mass appears negligible at first sight, its role should not be overlooked given its impact on muscle strength.

Caloric restriction and aerobic exercise in sarcopenic and non-sarcopenic obese women: an observational and retrospective study.

BACKGROUND: Sarcopenic obese (SO) individuals are a unique subset of subjects that combines obesity and sarcopenia. Traditional weight loss programmes including aerobic exercises may worsen their condition by further reducing their lean mass. The objective of this observational and retrospective study was to verify the effect of a mixed weight loss programme combining caloric restriction and exercise on body composition, and lipid-lipoprotein profile of obese women according to their sarcopenic status. METHODS: One hundred and forty-six obese women (body mass index ≥ 30 kg/m(2) and fat mass ≥ 40%) participated to the 3 week usual and institutionalized weight-reducing programme combining a dietary plan (1400 ± 200 kcal/day) and aerobic exercise (1 h/day, 6 days/week) of a specialized medical institution. The lean body mass index (LMI; lean mass/height(2)) was calculated, and women in the lowest tertile of LMI were considered SO. RESULTS: At baseline, SO women were older, and their body weight and LMI were lower than non-sarcopenic obese (N-SO) women (p < 0.05). N-SO and SO women similarly lost fat mass and improved their lipid-lipoprotein profile (p < 0.05), while differences in LMI between groups persisted at the end of the weight-reducing programme. Indeed, N-SO women lost lean mass (p < 0.05) while SO did not. CONCLUSIONS: These findings suggest that a short weight loss programme combining caloric restriction and aerobic exercise may significantly reduce fat mass and improve lipid-lipoprotein profile in obese women, independently of their sarcopenic status. Such programmes may have deleterious effects on lean mass in N-SO subjects, only.

Physical activity in advanced Parkinson's disease: impact of subthalamic deep brain stimulation.

BACKGROUND: Maintaining a physically active lifestyle promotes general health. Recent studies have demonstrated that patients with Parkinson's disease (PD) fail to meet the suggested levels of physical activity and that targeted interventions do not always improve this behavior. One validated treatment for motor symptoms in PD is subthalamic stimulation (STN DBS). OBJECTIVE: Assess whether motor symptom improvement following STN DBS translated into increased physical activity behavior. METHODS: Twenty patients with PD scheduled for bilateral STN DBS filled-out the Phone-FITT physical activity questionnaire and the SF-36 quality of life questionnaire prior to surgery and 6 to 9 months postoperatively. Data were compared to age- and gender-matched healthy controls. RESULTS: Our results demonstrate that PD patients' quality of life is significantly lower than healthy controls. While STN DBS improves motor symptoms in the intermediate term, it only improves some aspects of quality of life related to physical function. Furthermore, STN DBS does not modify physical activity behavior measured by the Phone-FITT, whether for household or recreational activities. CONCLUSION: The current study demonstrates that the motor improvements observed after STN DBS do not lead to systematic improvements in all aspects of quality of life or increased levels of physical activity. This highlights the need to develop and implement intervention strategies to promote an active lifestyle in this population, even if clinical improvement is evident following surgery.

The relationship between muscle fiber type-specific PGC-1α content and mitochondrial content varies between rodent models and humans.

PGC-1α regulates critical processes in muscle physiology, including mitochondrial biogenesis, lipid metabolism and angiogenesis. Furthermore, PGC-1α was suggested as an important regulator of fiber type determination. However, whether a muscle fiber type-specific PGC-1α content exists, whether PGC-1α content relates to basal levels of mitochondrial content, and whether such relationships are preserved between humans and classically used rodent models are all questions that have been either poorly addressed or never investigated. To address these issues, we investigated the fiber type-specific content of PGC-1α and its relationship to basal mitochondrial content in mouse, rat and human muscles using in situ immunolabeling and histochemical methods on muscle serial cross-sections. Whereas type IIa fibers exhibited the highest PGC-1α in all three species, other fiber types displayed a hierarchy of type IIx>I>IIb in mouse, type I = IIx> IIb in rat, and type IIx>I in human. In terms of mitochondrial content, we observed a hierarchy of IIa>IIx>I>IIb in mouse, IIa >I>IIx> IIb in rat, and I>IIa> IIx in human skeletal muscle. We also found in rat skeletal muscle that type I fibers displayed the highest capillarization followed by type IIa >IIx>IIb. Finally, we found in human skeletal muscle that type I fibers display the highest lipid content, followed by type IIa>IIx. Altogether, our results reveal that (i) the fiber type-specific PGC-1α and mitochondrial contents were only matched in mouse, (ii) the patterns of PGC-1α and mitochondrial contents observed in mice and rats do not correspond to that seen in humans in several respects, and (iii) the classical phenotypes thought to be regulated by PGC-1α do not vary exclusively as a function of PGC-1α content in rat and human muscles.

Subthalamic stimulation improves motor function but not home and neighborhood mobility.

OBJECTIVE: Subthalamic (STN) deep brain stimulation (DBS) is a recognized therapy for alleviating motor symptoms of Parkinson's disease (PD). However, little is known about its impact on mobility, an important component of quality of life (QoL). To address this issue, we assessed the impact of STN DBS on life-space mobility and QoL. METHODS: Twenty surgical patients with PD were assessed using mobility and QoL scales and the United Parkinson's disease rating scale, and results were compared before surgery and 6 to 9 months postoperatively. RESULTS: STN DBS significantly improved motor dysfunction but had a limited impact on measures of life-space mobility and QoL. INTERPRETATION: STN DBS improves motor function and some components of QoL. However, motor recovery does not translate into improved life-space in the intermediate term. In addition to a focus on motor function, multidisciplinary attention to increasing mobility may further improve QoL in the intermediate and long-term.

Identifying recreational physical activities associated with muscle quality in men and women aged 50 years and over.

BACKGROUND: Several studies conducted in a laboratory-related environment have shown that exercise is associated with increased muscle quality in older adults. The aim of the present study was to investigate whether recreational exercise may also be associated with muscle quality in men and women aged 50 years and over. METHODS: Data are from 312 individuals (215 women) aged 50 years and older. Body composition (dual-energy X-ray absorptiometry) and knee extension strength (KES) of the right leg (one repetition maximum) were assessed. Muscle quality (MQ) (KES/right lower limb lean mass) was calculated. Recreational exercises (duration and weekly amount) were determined by structured interview. RESULTS: The duration of the period during which participants practiced resistance activities was the only predictor of MQ (p = 0.018) and explained an additional 1.6 % of the variance in MQ, after controlling for age and gender. Furthermore, the weekly amount of practice of aerobic activities significantly interacted with age (p < 0.001) to determine MQ. CONCLUSIONS: Findings suggest that long-term engagement in resistance exercise is beneficial for muscle quality and should be encouraged. Furthermore, beyond 60 years, aerobic activities also seem to be positively associated with muscle quality.

Exploring the role of muscle mass, obesity, and age in the relationship between muscle quality and physical function.

BACKGROUND: Divergent conclusions emerge from the literature regarding the relationship between muscle quality (defined as muscle strength per unit of muscle mass) and physical function. These contrasted results may be due to the influence of factors such as age, obesity, and muscle mass itself. Consequently, the aim of the present study was to explore the role of these factors in the relationship between muscle quality (MQ) and physical function. METHODS: Data are from 312 individuals (97 men and 215 women) aged 50 years and older. Body composition (dual energy X-ray absorptiometry) and knee extension strength of the right leg (1 repetition maximum) were assessed. Appendicular lean body mass index (AppLBMI) and MQ (knee extension strength /right leg lean mass) were calculated. A composite score of physical function was created based on the timed up-and-go, alternate step, sit-to-stand, and balance tests. RESULTS: MQ was significantly associated with physical function when AppLBMI (ß = 0.179; P = .004) and body mass index (BMI) (ß = 0.178; P = .003), but not age (ß = 0.065; P = .26), were included in regression analysis. AppLBMI (ß = 0.221; P < .001), BMI (ß = 0.234; P < .001), and age (ß = 0.134; P = .018) significantly interacted with MQ to determine physical function. CONCLUSIONS: Our results show that muscle mass, obesity, and age influence the relationship between MQ and physical function, suggesting that these factors should be taken into account when interpreting MQ. Even so, higher levels of MQ were associated with higher physical function scores. Nutritional and physical activity interventions may be designed in this regard.

Increased sensitivity to mitochondrial permeability transition and myonuclear translocation of endonuclease G in atrophied muscle of physically active older humans.

Mitochondrial dysfunction is implicated in skeletal muscle atrophy and dysfunction with aging, with strong support for an increased mitochondrial-mediated apoptosis in sedentary rodent models. Whether this applies to aged human muscle is unknown, nor is it clear whether these changes are caused by sedentary behavior. Thus, we examined mitochondrial function [respiration, reactive oxygen species (ROS) emission, and calcium retention capacity (CRC)] in permeabilized myofibers obtained from vastus lateralis muscle biopsies of healthy physically active young (23.7±2.7 yr; mean±SD) and older (71.2±4.9 yr) men. Although mitochondrial ROS and maximal respiratory capacity were unaffected, the acceptor control ratio was reduced by 18% with aging, suggesting mild uncoupling of oxidative phosphorylation. CRC was reduced by 50% with aging, indicating sensitization of the mitochondrial permeability transition pore (mPTP) to apoptosis. Consistent with the mPTP sensitization, older muscles showed a 3-fold greater fraction of endonuclease G (a mitochondrial proapoptotic factor)-positive myonuclei. Aged muscles also had lower mitophagic potential, based on a 43% reduction in Parkin to the voltage-dependent anion channel (VDAC) protein ratio. Collectively, these results show that mitochondrial-mediated apoptotic signaling is increased in older human muscle and suggest that accumulation of dysfunctional mitochondria with exaggerated apoptotic sensitivity is due to impaired mitophagy.

Muscle quantity is not synonymous with muscle quality.

BACKGROUND: Greater muscle mass can generally produce greater muscle strength. However, whether higher muscle mass is associated with higher muscle quality (muscle strength relative to muscle mass) remains unknown. Furthermore, the nature of this relationship, and how their interaction determines the presence of functional impairments are unknown. This article aims to address these issues. METHODS: Secondary data analysis including 1219 women aged 75 years and older of the Toulouse ÉPIDemiologie de l'OSteoporose cohort study. Body composition (dual energy X-ray absorptiometry), handgrip, and knee extension strength were assessed. Physical function was measured using the chair stand test as well as the usual and fast gait speed tests. Participants were also asked if they experienced any difficulty in performing functional tasks. RESULTS: Upper- and lower-body muscle quality (r = -0.42, P < .001 and r = -0.16, P < .001, respectively) were significantly and negatively correlated with appendicular skeletal muscle mass index (ASMI). Independently of ASMI, individuals with high muscle quality had low risks of functional impairments (odds ratio <0.74), whereas individuals with high ASMI but low muscle quality had high risks of impairments (odds ratio >1.27). CONCLUSIONS: This inverse relationship between muscle mass and quality implies that sarcopenic individuals have better muscle quality than nonsarcopenic individuals. Results also suggest that high muscle quality may compensate for low ASMI with respect to functional impairments. Physical activity may potentially be involved in this relationship.

Toward a sex-specific relationship between muscle strength and appendicular lean body mass index?

BACKGROUND: In spite of some dissociation between muscle mass and strength, muscle strength is often used as a proxy to identify individuals with low muscle mass (sarcopenia). Thus, the aim of the present study was to investigate the relationship between muscle strength and the appendicular lean body mass index (app LBMI). METHODS: One hundred and five individuals were recruited. Knee extension and handgrip strength were measured. Body composition was assessed by DXA. App LBMI was calculated as appendicular lean body mass divided by height squared. RESULTS: At le level of the entire cohort, both handgrip (r = 0.73; p < 0.001) and knee extension strength (r = 0.57; p < 0.001) were associated with app LBMI. However, in women, knee extension strength (r = 0.32; p < 0.05) but not handgrip strength (r = 0.14; p = 0.35) was associated with app LBMI; while in men, handgrip strength (r = 0.43; p < 0.01) but not knee extension strength (r = 0.27; p = 0.09) was associated with app LBMI. CONCLUSIONS: Muscle strength appears to be associated with lean body mass; however, handgrip strength may be preferentially used in men and knee extension strength in women to detect sarcopenic individuals. Future larger studies are now needed to confirm our findings and their clinical relevance.

Clinical relevance of different muscle strength indexes and functional impairment in women aged 75 years and older.

BACKGROUND: Muscle mass index has long been used as a useful index to evaluate the risks of developing functional impairments. However, there is evidence that other indexes (particularly muscle strength-based indexes) may be more relevant. Thus, the purpose of this study was to compare the association between different indexes of muscle mass or strength with self-reported and measured functional performance to determine which index would be clinically relevant to detect individuals at risk of functional impairments. METHODS: Data are from 1,462 women aged 75 years and older recruited in the Toulouse EPIDémiologie de l'OStéoporose cohort. Body composition (assessed by dual energy x-ray absorptiometry), handgrip, and knee extension strength were assessed. Physical function was measured using the chair stand test as well as the usual and fast gait speed tests. Participants were also asked if they experienced any difficulty at performing functional tasks. RESULTS: Results showed that knee extension strength relative to body weight was the strongest correlate of physical function measures (.30 < r < .40). Women in the lowest quartile of knee extension strength relative to body weight were 5.9-, 24.7-, 12.1-, and 20.9-fold, respectively, more likely to present impairments at self-reported activities, chair stand test, and usual and fast gait speed compared with women in the highest quartile, respectively. CONCLUSIONS: Knee extension strength relative to body weight appears to be well associated with self-reported difficulties and functional impairments. A threshold between 2.78 and 2.86 (knee extension strength [kPa]/body weight [kg]), determined using receiver operating characteristics curves analysis, may be a potential cut point to discriminate women presenting higher functional impairments.