Associations between muscle strength, spirometric pulmonary function and mobility in healthy older adults.

Pathological obstruction in lungs leads to severe decreases in muscle strength and mobility in patients suffering from chronic obstructive pulmonary disease. The purpose of this study was to investigate the interdependency between muscle strength, spirometric pulmonary functions and mobility outcomes in healthy older men and women, where skeletal muscle and pulmonary function decline without interference of overt disease. A total of 135 69- to 81-year-old participants were recruited into the cross-sectional study, which was performed as a part of European study MyoAge. Full, partial and no mediation models were constructed to assess the interdependency between muscle strength (handgrip strength, knee extension torque, lower extremity muscle power), spirometric pulmonary function (FVC, FEV1 and FEF50) and mobility (6-min walk and Timed Up and Go tests). The models were adjusted for age, sex, total fat mass, body height and site of enrolment. Partial mediation models, indicating both direct and pulmonary function mediated associations between muscle strength and mobility, fitted best to the data. Greater handgrip strength was significantly associated with higher FVC, FEV1 and FEF50 (p < 0.05). Greater muscle power was significantly associated with better performance in mobility tests. Results suggest that decline in mobility with aging may be caused by decreases in both muscle strength and power but also mediated through decreases in spirometric pulmonary function. Future longitudinal studies are warranted to better understand how loss of function and mass of the respiratory muscles will affect pulmonary function among older people and how these changes are linked to mobility decline.

Diagnostic criteria for sarcopenia and physical performance.

Relative and absolute muscle mass and muscle strength are used as diagnostic criteria for sarcopenia. We aimed to assess which diagnostic criteria are most associated with physical performance in 180 young (18-30 years) and 281 healthy old participants (69-81 years) of the European study MYOAGE. Diagnostic criteria included relative muscle mass (total or appendicular lean mass (ALM) as percentage of body mass), absolute muscle mass (ALM/height squared and total lean mass), knee extension torque, and handgrip strength. Physical performance comprised walking speed, Timed Up and Go test (TUG), and in a subgroup physical fitness. Diagnostic criteria for sarcopenia and physical performance were standardized, and the associations were analyzed using linear regression models stratified by age category, with adjustments for age, gender, and country. In old participants, relative muscle mass was associated with faster walking speed, faster TUG, and higher physical fitness (all p < 0.001). Absolute muscle mass was not associated with physical performance. Knee extension torque and handgrip strength were associated with faster walking speed (both p ≤ 0.003). Knee extension torque was associated with TUG (p = 0.001). Knee extension torque and handgrip strength were not associated with physical fitness. In young participants, there were no significant associations between diagnostic criteria for sarcopenia and physical performance, except for a positive association between relative muscle mass and physical fitness (p < 0.001). Relative muscle mass, defined as lean mass or ALM percentage, was most associated with physical performance. Absolute muscle mass including ALM/height squared was not associated with physical performance. This should be accounted for when defining sarcopenia.

Diagnostic measures for sarcopenia and bone mineral density.

SUMMARY: Currently used diagnostic measures for sarcopenia utilize different measures of muscle mass, muscle strength, and physical performance. These diagnostic measures associate differently to bone mineral density (BMD), as an example of muscle-related clinical outcome. These differences should be taken into account when studying sarcopenia. INTRODUCTION: Diagnostic measures for sarcopenia utilize different measures of muscle mass, muscle strength, and physical performance. To understand differences between these measures, we determined the association with respect to whole body BMD, as an example of muscle-related clinical outcome. METHODS: In the European cross-sectional study MYOAGE, 178 young (18-30 years) and 274 healthy old participants (69-81 years) were recruited. Body composition and BMD were evaluated using dual-energy X-ray densitometry. Diagnostic measures for sarcopenia were composed of lean mass as percentage of body mass, appendicular lean mass (ALM) as percentage of body mass, ALM divided by height squared (ALM/height(2)), knee extension torque, grip strength, walking speed, and Timed Up and Go test (TUG). Linear regression models were stratified for sex and age and adjusted for age and country, and body composition in separate models. RESULTS: Lean mass and ALM/height(2) were positively associated with BMD (P < 0.001). Significance remained in all sex and age subgroups after further adjustment for fat mass, except in old women. Lean mass percentage and ALM percentage were inversely associated with BMD in old women (P < 0.001). These inverse associations disappeared after adjustment for body mass. Knee extension torque and handgrip strength were positively associated with BMD in all subgroups (P < 0.01), except in old women. Walking speed and TUG were not related to BMD. CONCLUSIONS: The associations between diagnostic measures of sarcopenia and BMD as an example of muscle-related outcome vary widely. Differences between diagnostic measures should be taken into account when studying sarcopenia.

Signalling pathways regulating muscle mass in ageing skeletal muscle: the role of the IGF1-Akt-mTOR-FoxO pathway.

During ageing skeletal muscles undergo a process of structural and functional remodelling that leads to sarcopenia, a syndrome characterized by loss of muscle mass and force and a major cause of physical frailty. To determine the causes of sarcopenia and identify potential targets for interventions aimed at mitigating ageing-dependent muscle wasting, we focussed on the main signalling pathway known to control protein turnover in skeletal muscle, consisting of the insulin-like growth factor 1 (IGF1), the kinase Akt and its downstream effectors, the mammalian target of rapamycin (mTOR) and the transcription factor FoxO. Expression analyses at the transcript and protein level, carried out on well-characterized cohorts of young, old sedentary and old active individuals and on mice aged 200, 500 and 800 days, revealed only modest age-related differences in this pathway. Our findings suggest that during ageing there is no downregulation of IGF1/Akt pathway and that sarcopenia is not due to FoxO activation and upregulation of the proteolytic systems. A potentially interesting result was the increased phosphorylation of the ribosomal protein S6, indicative of increased activation of mTOR complex1 (mTORC1), in aged mice. This result may provide the rationale why rapamycin treatment and caloric restriction promote longevity, since both interventions blunt activation of mTORC1; however, this change was not statistically significant in humans. Finally, genetic perturbation of these pathways in old mice aimed at promoting muscle hypertrophy via Akt overexpression or preventing muscle loss through inactivation of the ubiquitin ligase atrogin1 were found to paradoxically cause muscle pathology and reduce lifespan, suggesting that drastic activation of the IGF1-Akt pathway may be counterproductive, and that sarcopenia is accelerated, not delayed, when protein degradation pathways are impaired.

Diagnostic criteria for sarcopenia relate differently to insulin resistance.

Skeletal muscle is important in insulin-stimulated glucose uptake. Sarcopenia is, therefore, a possible risk factor for insulin resistance. Currently, different diagnostic criteria for sarcopenia include low muscle mass, muscle strength, and walking speed. We assessed these muscle characteristics in relation to insulin resistance in nondiabetics. This cross-sectional study included 301 nondiabetics, mean age 65.9 years. Area under curve (AUC) calculations of insulin and glucose from a 2-h oral glucose tolerance test (OGTT) and homeostasis model assessment of insulin resistance (HOMA-IR) were used as measures of insulin resistance. Muscle characteristics were relative muscle mass (total or appendicular lean mass (ALM) as percentage of body mass), absolute muscle mass (ALM/height(2) and total lean mass), handgrip strength, and walking speed. All muscle characteristics were standardized and analyzed in linear regression models, stratified by gender. For both males and females, relative muscle mass was inversely associated with AUC insulin, AUC glucose, and HOMA-IR (ALM percentage all p ≤ 0.004). Absolute muscle mass was positively associated with AUC insulin and HOMA-IR (ALM/height(2) all p < 0.001) but not with AUC glucose. Adjustments for fat mass attenuated aforementioned associations. There were no associations between handgrip strength and insulin resistance. Walking speed was inversely associated with AUC insulin in males (p = 0.032). The association between muscle characteristics and insulin resistance was strongest for relative muscle mass. Diagnostic criteria for sarcopenia relate differently to insulin resistance. The role of muscle tissue as an internal glucose-regulating organ is better reflected by relative muscle mass than by absolute muscle mass, muscle strength, or walking speed.

Defining sarcopenia: the impact of different diagnostic criteria on the prevalence of sarcopenia in a large middle aged cohort.

Sarcopenia, low muscle mass, is an increasing problem in our ageing society. The prevalence of sarcopenia varies extremely between elderly cohorts ranging from 7% to over 50%. Without consensus on the definition of sarcopenia, a variety of diagnostic criteria are being used. We assessed the degree of agreement between seven different diagnostic criteria for sarcopenia based on muscle mass and handgrip strength, described in literature. In this cross-sectional study, we included men (n=0325) and women (n=0329) with complete measurements of handgrip strength and body composition values as measured by bioimpedance analysis within the Leiden Longevity Study. Prevalence of sarcopenia was stratified by gender and age. In men (mean age 64.5 years), the prevalence of sarcopenia with the different diagnostic criteria ranged from 0% to 20.8% in the lowest age category (below 60 years), from 0%to 31.2% in the middle (60 to 69 years) and from 0% to 45.2% in the highest age category (above 70 years). In women (mean age 61.8 years), the prevalence of sarcopenia ranged from 0% to 15.6%, 0% to 21.8% and 0% to 25.8% in the lowest, middle and highest age category, respectively. Only one participant (0.2%) was identified having sarcopenia according to all diagnostic criteria that marked prevalence above 0%. We conclude that the prevalence of sarcopenia is highly dependent on the applied diagnostic criteria. It is necessary to reach a consensus on the definition of sarcopenia in order to make studies comparable and for implementation in clinical care.

Chronology of age-related disease definitions: osteoporosis and sarcopenia.

Low muscle mass at older age has been associated with functional impairments, cognitive decline and mortality. The term sarcopenia, coined in 1988, has been used interchangeably to describe low muscle mass, strength, and function. Without a well defined definition, results of studies using the term sarcopenia cannot be compared. Difficulties in defining sarcopenia parallel the history of defining osteoporosis. To understand critical steps that are needed to reach consensus in defining age-related diseases, we have identified milestones in the history of defining osteoporosis and compared these to sarcopenia. As a result, the main missing steps in the process of defining sarcopenia are: specific treatment options, pharmaceutical interest, and public awareness. Similar to osteoporosis being defined as 'low bone mineral density', the term sarcopenia should be reserved for 'low muscle mass'. Consensus must be reached regarding the diagnostic criteria to quantify muscle mass, correction factors, and reference populations used to define cut-off values of muscle mass.