Sarcopenic obesity (SO) is a combination of obesity and sarcopenia that primarily develops in older people. Patients with SO have high fat mass, low muscle mass, low muscle strength, and low physical function. SO relates to metabolic syndrome and an increased risk of morbimortality. The prevalence of SO varies because of lacking consensus criteria regarding its definition and the methodological difficulty in diagnosing sarcopenia and obesity. SO includes systemic alterations such as insulin resistance, increased proinflammatory cytokines, age-associated hormonal changes, and decreased physical activity at pathophysiological levels. Interestingly, these alterations are influenced by oxidative stress, which is a critical factor in altering muscle function and the generation of metabolic dysfunctions. Thus, oxidative stress in SO alters muscle mass, the signaling pathways that control it, satellite cell functions, and mitochondrial and endoplasmic reticulum activities. Considering this background, our objectives in this review are to describe SO as a highly prevalent condition and look at the role of oxidative stress in SO pathophysiology.

/pdf/the-critical-role-of-oxidative-stress-in-sarcopenic-obesity-500l8cxq31.pdf

The Critical Role of Oxidative Stress in Sarcopenic Obesity

Aging and obesity are two global concerns in public health. Sarcopenic obesity (SO), defined as the combination of age-related sarcopenia and obesity, has become a pressing issue. This systematic review and meta-analysis summarize the current clinical evidence relevant to SO. PubMed, Embase, and Web of Science were searched, and 106 clinical studies with 167,151 elderlies were included. The estimated prevalence of SO was 9% in both men and women. Obesity was associated with 34% reduced risk of sarcopenia (odds ratio [OR] 0.66, 95% CI 0.48-0.91; p < 0.001). The pooled hazard ratio (HR) of all-cause mortality was 1.51 (95% CI 1.14-2.02; p < 0.001) for people with SO compared with healthy individuals. SO was associated with increased risk of cardiovascular disease and related mortality, metabolic disorders, cognitive impairment, arthritis, functional limitation, and lung diseases (all ORs > 1.0, p < 0.05). The attenuated risk of sarcopenia in elderlies with obesity ("obesity paradox") was dependent on higher muscle mass and strength. Apart from unifying the diagnosis of SO, more research is needed to subphenotype people with obesity and sarcopenia for individualized treatment. Meanwhile, the maintenance of proper body composition of muscle and fat may delay or attenuate the adverse outcomes of aging. 

Deciphering the “obesity paradox” in the elderly: A systematic review and meta‐analysis of sarcopenic obesity

Obesity may aggravate the effects of sarcopenia on skeletal muscle structure and function in the elderly, but no study has attempted to identify the gene variants associated with sarcopenia in obese women. Therefore, the aims of the present study were to: (1) describe neuromuscular function in sarcopenic and non-sarcopenic women with or without obesity; (2) identify gene variants associated with sarcopenia in older obese women. In 307 Caucasian women (71 ± 6 years, 66.3 ± 11.3 kg), skeletal muscle mass was estimated using bioelectric impedance, and function was tested with a 30 s one-leg standing-balance test. Biceps brachii thickness and vastus lateralis cross-sectional area (VLACSA) were measured with B-mode ultrasonography. Handgrip strength, maximum voluntary contraction elbow flexion (MVCEF), and knee extension torque (MVCKE) were measured by dynamometry, and MVCKE/VLACSA was calculated. Genotyping was performed for 24 single-nucleotide polymorphisms (SNPs), selected based on their previous associations with muscle-related phenotypes. Based on sarcopenia and obesity thresholds, groups were classified as sarcopenic obese, non-sarcopenic obese, sarcopenic non-obese, or non-sarcopenic non-obese. A two-way analysis of covariance was used to assess the main effects of sarcopenia and obesity on muscle-related phenotypes and binary logistic regression was performed for each SNP to investigate associations with sarcopenia in obesity. There were no significant obesity * sarcopenic status interactions for any of the investigated muscle-related phenotypic parameters. Neither sarcopenia nor obesity had a significant effect on biceps brachii thickness, but sarcopenia was associated with lower VLACSA (p = 0.003). Obesity was associated with lower MVCEF (p = 0.032), MVCKE (p = 0.047), and MVCKE/VLACSA (p = 0.012) with no significant effect of sarcopenia. Adjusted for age and height, three SNPs (ACTN3 rs1815739, MTHFR rs1801131, and MTHFR rs1537516) were associated with sarcopenia in obese participants. Sarcopenia was associated with a smaller muscle size, while obesity resulted in a lower muscle quality irrespective of sarcopenia. Three gene variants (ACTN3 rs1815739, MTHFR rs1801131, and MTHFR rs1537516) suspected to affect muscle function, homocysteine metabolism, or DNA methylation, respectively, were associated with sarcopenia in obese elderly women. Understanding the skeletal muscle features affected by sarcopenia and obesity, and identification of genes related to sarcopenia in obese women, may facilitate early detection of individuals at particular risk of sarcopenic obesity.

Sarcopenia, obesity, and sarcopenic obesity: Relationship with skeletal muscle phenotypes and single nucleotide polymorphisms

Background: An increasing body of evidence indicates that the phase angle (PhA) can be applied as a marker of nutritional status, disease prognosis, and mortality probability. Still, it is not known whether PhA can be used as an indicator of muscular quantity and strength and maximal aerobic capacity in overweight/obese former highly active individuals, an understudied population. This study aimed to analyze the association between PhA with skeletal muscle mass, maximal isometric strength, and maximal aerobic capacity through VO2max, in overweight/obese and inactive former athletes. Methods: Cross-sectional information of 94 (62 males) former adult athletes (age: 43.1 ± 9.4 years old; body mass index: 31.4 ± 4.8 kg/m2) taking part in a weight-loss clinical trial was analyzed. Total fat and fat-free mass were determined by dual-energy X-ray absorptiometry, while skeletal muscle mass was predicted from appendicular lean soft tissue. Values for upper- and lower-body maximal isometric strength were assessed by handgrip and leg press dynamometry. VO2max was determined by indirect calorimetry through a graded exercise test performed on a treadmill. Results: PhA was associated with skeletal muscle mass (r = 0.564, p < 0.001), upper-body strength (r = 0.556, p < 0.001), lower-body strength (r = 0.422, p < 0.001), and VO2max (r = 0.328, p = 0.013). These relationships remained significant for skeletal muscle mass (β = 2.158, p = 0.001), maximal isometric strength (upper-body: β = 2.846, p = 0.012; low-er-body: β = 24.209, p = 0.041) after adjusting for age, sex, and fat mass but not for VO2max (β = −0.163, p = 0.098). Conclusion: Our findings indicated that former athletes with higher values of PhA exhibited greater muscle mass and strength, despite sex, age, and body composition, which suggests that this simple raw BI parameter can be utilized as an indicator of muscle quantity and functionality in overweight/obese former athletes.

Phase Angle Is a Marker of Muscle Quantity and Strength in Overweight/Obese Former Athletes.

Predictive equation for assessing appendicular lean soft tissue mass using bioelectric impedance analysis in older adults: Effect of body fat distribution.

Obesity is a global epidemic and coupled with the unprecedented growth of the world's older adult population, a growing number of individuals are both old and obese. Whilst both ageing and obesity are associated with an increased prevalence of chronic health conditions and a substantial economic burden, evidence suggests that the coincident effects exacerbate negative health outcomes. A significant contributor to such detrimental effects may be the reduction in the contractile performance of skeletal muscle, given that poor muscle function is related to chronic disease, poor quality of life and all-cause mortality. Whilst the effects of ageing and obesity independently on skeletal muscle function have been investigated, the combined effects are yet to be thoroughly explored. Given the importance of skeletal muscle to whole-body health and physical function, the present study sought to provide a review of the literature to: (1) summarise the effect of obesity on the age-induced reduction in skeletal muscle contractile function; (2) understand whether obesity effects on skeletal muscle are similar in young and old muscle; (3) consider the consequences of these changes to whole-body functional performance; (4) outline important future work along with the potential for targeted intervention strategies to mitigate potential detrimental effects.

Age-Related Skeletal Muscle Dysfunction Is Aggravated by Obesity: An Investigation of Contractile Function, Implications and Treatment.

This study examined the effect of stimulation frequency (140, 200, 230 and 260 Hz) on isometric force, work loop (WL) power, and the fatigue resistance of extensor digitorum longus (EDL) muscle (n=32), isolated from 8-10-week-old CD-1 female mice. Stimulation frequency had significant effects on isometric properties of isolated mouse EDL, whereby increasing stimulation frequency evoked increased isometric force, quicker activation, and prolonged relaxation (P <0.047), until 230 Hz and above, thereafter force and activation did not differ (P >0.137). Increasing stimulation frequency increased maximal WL power output (P <0.001; 140 Hz, 71.3±3.5; 200 Hz, 105.4±4.1; 230 Hz, 115.5±4.1; 260 Hz, 121.1±4.1 W.kg-1), but resulted in significantly quicker rates of fatigue during consecutive WL's (P <0.004). WL shapes indicate impaired muscle relaxation at the end of shortening and subsequent increased negative work appeared to contribute to fatigue at 230 and 260 Hz, but not at lower stimulation frequencies. Cumulative work was unaffected by stimulation frequency, except at the start of fatigue protocol where 230 and 260 Hz produced more work than 140 Hz (P <0.039). We demonstrate that stimulation frequency affects force, power, and fatigue, but effects are not uniform between different assessments of contractile performance. Therefore, future work examining contractile properties of isolated skeletal muscle should consider increasing stimulation frequency beyond that needed for maximal force when examining maximal power but utilise a sub-maximal stimulation frequency for fatigue assessments to avoid high degree of negative work atypical of in vivo function.

https://pure.coventry.ac.uk/ws/files/60637502/Post_Print.pdf

Effect of stimulation frequency on force, power, and fatigue of isolated mouse extensor digitorum longus muscle.

The present study uniquely examined the influence of old age and adiposity on maximal concentric and eccentric torque and fatigue of the elbow and knee (KF, KE) flexors and extensors. Forty males w...

/pdf/the-effects-of-high-adiposity-on-concentric-and-eccentric-2s5x8ub5oi.pdf

The Effects of High Adiposity on Concentric and Eccentric Muscle Performance of Upper and Lower Limb Musculature in Young and Old Adults

It remains unclear why some patients develop heart failure without evidence of structural damage. One theory relates to impaired myocardial energetics and ventricular-arterial decoupling as the heart works against adverse mechanical load. In this original study, we propose the novel concept of myocardial fatigue to capture this phenomenon and aim to investigate this using human cardiomyocytes subjected to a modern work-loop contractility model that closely mimics in vivo cardiac cycles. This proof-of-concept study (NCT04899635) will use human myocardial tissue samples from patients undergoing cardiac surgery to develop a reproducible protocol to isolate robust calcium-tolerant cardiomyocytes. Thereafter, work-loop contractility experiments will be performed over a range of preload, afterload and cycle frequency as a function of time to elicit any reversible reduction in contractile performance (i.e. fatigue). This will provide novel insight into mechanisms behind heart failure and myocardial recovery and serve as a valuable research platform in translational cardiovascular research. 

/pdf/profiling-the-biomechanical-responses-to-workload-on-the-26142wse.pdf

Profiling the Biomechanical Responses to Workload on the Human Myocyte to Explore the Concept of Myocardial Fatigue and Reversibility: Rationale and Design of the POWER Heart Failure Study

Sharn Shelley

Papers

Age-Related Skeletal Muscle Dysfunction Is Aggravated by Obesity: An Investigation of Contractile Function, Implications and Treatment.

Effect of stimulation frequency on force, power, and fatigue of isolated mouse extensor digitorum longus muscle.

The Effects of High Adiposity on Concentric and Eccentric Muscle Performance of Upper and Lower Limb Musculature in Young and Old Adults

Profiling the Biomechanical Responses to Workload on the Human Myocyte to Explore the Concept of Myocardial Fatigue and Reversibility: Rationale and Design of the POWER Heart Failure Study