Strength training for the prevention and treatment of sarcopenia

There is a progressive loss of muscle strength, muscle mass and muscle quality with advanced age, which results in a condition known as sarcopenia. In this review, the authors outline the magnitude of these losses, their functional consequences, and the efficacy of strength training (ST) as an intervention strategy for delaying, preventing or reversing the effects of sarcopenia. The question of whether sex differences and genetics influence the effects of sarcopenia and responses to ST are also discussed. Although many potential mechanisms for sarcopenia exist, their specific contributions are still unknown. Nevertheless, proposed mechanisms of sarcopenia are outlined and, where information is available, we examine the effects of ST on these potential mechanisms, which include neurogenic factors, anabolic hormones, protein synthesis, gene expression, muscle morphology, and muscle regeneration. Finally, the potential impact of genetics in the muscle response to both sarcopenia and ST is discussed. The evidence presented suggests that ST is an effective intervention for improving strength, muscle mass and muscle quality and delaying the onset of physical disability in the elderly. However, sex differences and genetic factors may play an important role in determining the muscular response to aging and ST.     

Research hypotheses on muscle wasting, aging, loss of function and disability

Advancing age is accompanied by modifications in body composition such as increase in fat and decrease in bone and muscle mass. Loss of muscle mass or sarcopenia is characterized by a decrease in the total number of muscle fibers, a reduced cross-sectional area of the thigh, and decreased muscle density associated with increased intramuscular fat. Loss of skeletal muscle mass may be a common pathway by which multiple diseases contribute to the risk of disability. Decreases in muscle mass are associated with an increased risk of morbidity, mortality and disability in old age, but the mechanisms by which this occurs are not fully understood. Inflammatory cytokines interfere with muscle contraction and are linked with sarcopenia. Recent evidence showing that decline in left ventricular function is accompanied by sarcopenia and an increase in cytokines might help to understand the role of cytokines in muscle loss in aging and disease. The Health and Body Changes (Health ABC) study, a large population-based cohort study sponsored by the National Institute on Aging, will prospectively address the issues related to sarcopenia and incident disability. Defining modifiable risk factors of sarcopenia is the first step towards the identification of interventions for preventing or reversing disability in older persons.     

Discovering pathways of sarcopenia in older adults: A role for insulin resistance on mitochondria dysfunction

The precise cause of sarcopenia, skeletal muscle loss and strength, in older persons is unknown. However, there is a strong evidence for muscle loss due to insulin resistance as well as mitochondrial dysfunction over aging. Considering that epidemiological studies have underlined that insulin resistance may have a specific role on skeletal muscle fibre atrophy and mitochondrial dysfunction has also been extensively shown to have a pivotal role on muscle loss in older persons, a combined pathway may not be ruled out. Considering that there is growing evidence for an insulin-related pathway on mitochondrial signaling, we hypothesize that a high degree of insulin resistance will be associated with the development of sarcopenia through specific alterations on mitochondrial functioning. This paper will highlight recent reviews regarding the link between skeletal muscle mitochondrial dysfunction and insulin resistance. We will specifically emphasize possible steps involved in sarcopenia over aging, including potential biomolecular mechanisms of insulin resistance on mitochondrial functioning.     

Independent and combined effects of exercise and vitamin D on muscle morphology, function and falls in the elderly

Regular exercise, particularly progressive resistance training (PRT), is recognized as one of the most effective strategies to prevent age-related muscle loss (sarcopenia), but its effects on muscle function are mixed. However, emerging data indicates that high velocity PRT (fast concentric muscle contractions) is more effective for improving functional outcomes than traditional PRT. In terms of falls prevention, high-challenging balance training programs appear to be most effective. There is also compelling evidence that supplemental vitamin D is an effective therapeutic option for falls prevention. The findings from a recent meta-analysis revealed that supplemental vitamin D at a dose of at least 700-1,000 IU/d or an achieved serum 25(OH)D level of at least 60 nmol/L was associated with reduced falls risk among older individuals. Based on these findings, it is possible that the combination of exercise and vitamin D could have a synergistic effect on muscle morphology and function, particularly since both interventions have been shown to have beneficial effects on type II "fast twitch" muscle fibers and systemic inflammation, which have both been linked to losses in muscle mass and function. Unfortunately however, the findings from the limited number of factorial 2 × 2 design RCTs indicate that additional vitamin D does not enhance the effects of exercise on measures of muscle morphology, function or falls risk. However, none of these trials were adequately powered to detect a "synergistic" effect between the two treatment strategies, but it is likely that if an exercise-by-vitamin D interaction does exist, it may be limited to situations when vitamin D deficiency/insufficiency is corrected. Further targeted research in "high risk" groups is still needed to address this question, and evaluate whether there is a threshold level of serum 25(OH)D to maximize the effects of exercise on muscle and falls risk.     

Designing Phase II B trials in sarcopenia: the best target population

Despite the existing limitations and controversies regarding the definition of sarcopenia and its clinical consequences, the current scientific evidence strongly suggests that muscle decline is a primary determinant of the disabling process (and likely of other major health-related events). In fact, the muscle loss (in terms of mass as well as strength) occurring with aging has been growingly associated with mobility impairment and disability in older persons. Unfortunately, current evidence is mainly from observational studies. Times are mature to begin testing interventions aimed at modifying the sarcopenia process through the design and development of specific clinical trials. Considering the emergence of many promising interventions towards this age-related condition (e.g., physical exercise [in particular, resistance training], testosterone, antioxidant supplementations), the need for Phase II trial designs is high. In the present report, we discuss which are the major issues related to the design of Phase II clinical trials on sarcopenia with particular focus on the participant’s characteristics to be considered as possible inclusion and exclusion criteria.     

Nutritional Supplements in Support of Resistance Exercise to Counter Age-Related Sarcopenia

Age-related sarcopenia, composed of myopenia (a decline in muscle mass) and dynapenia (a decline in muscle strength), can compromise physical function, increase risk of disability, and lower quality of life in older adults. There are no available pharmaceutical treatments for this condition, but evidence shows resistance training (RT) is a viable and relatively low-cost treatment with an exceptionally positive side effect profile. Further evidence suggests that RT-induced increases in muscle mass, strength, and function can be enhanced by certain foods, nutrients, or nutritional supplements. This brief review focuses on adjunctive nutritional strategies, which have a reasonable evidence base, to enhance RT-induced gains in outcomes relevant to sarcopenia and to reducing risk of functional declines.     

Effect of protein intake on bone and muscle mass in the elderly

The aging process is frequently characterized by an involuntary loss of muscle (sarcopenia) and bone (osteoporosis) mass. Both chronic diseases are associated with decreased metabolic rate, increased risk of falls/fracture, and, as a result, increased morbidity and loss of independence in the elderly. The quality and quantity of protein intake affects bone and muscle mass in several ways and there is evidence that increased essential amino acid or protein availability can enhance muscle protein synthesis and anabolism, as well as improve bone homeostasis in older subjects. A thorough evaluation of renal function is important, since renal function decreases with age. Finally, protein and calcium intake should be considered in the prevention or treatment of the chronic diseases osteoporosis and sarcopenia.     

Diet Quality and Measures of Sarcopenia in Developing Economies: A Systematic Review

Sarcopenia refers to common age-related changes characterised by loss of muscle mass, strength, and physical performance that results in physical disability, poorer health status, and higher mortality in older adults. Diet quality is indicated as a potentially modifiable risk factor for sarcopenia. However, the association between diet quality and sarcopenia in developing economies appears to be conflicting. Hence, we conducted a systematic review of the literature from developing economies examining the relationship between diet quality and at least one of the three components of sarcopenia, including muscle mass, muscle strength, and physical performance, and the overall risk of sarcopenia. No restrictions on age and study design were employed. We identified 15 studies that met review inclusion criteria. There was heterogeneity among the studies in the diet quality metric used and sarcopenia-related outcomes evaluated. Longitudinal evidence and studies relating diet quality to a holistic definition of sarcopenia were lacking. Although limited and predominantly cross-sectional, the evidence consistently showed that diet quality defined by diversity and nutrient adequacy was positively associated with sarcopenia components, such as muscle mass, muscle strength, and physical performance.     

Evolution of sarcopenia research

The term "saropenia" was coined by Irwin Rosenberg in 1989 to refer to age-related loss of skeletal muscle mass. The purpose of this current opinion is to provide an evolutionary overview of sarcopenia research since 1989. This includes the creation of an operational definition of sarcopenia; consideration of the impacts of sarcopenia on physical function, chronic disease, and mortality risk; the distinction between the process of sarcopenia and the process of age-related loss of muscle strength, a phenomenon that has recently been termed dynapenia; a comparison of the independent effects of sarcopenia and dynapenia on physical function, chronic disease, and mortality risk; and consideration of the combined influence of sarcopenia and dynapenia with obesity (i.e., sarcopenic-obesity and dynapenic-obesity) on physical function, chronic disease, and mortality risk.     

The role of hormones, cytokines and heat shock proteins during age-related muscle loss

Ageing is associated with a progressive decline of muscle mass, strength, and quality, a condition known as sarcopenia. Due to the progressive ageing of western populations, age-related sarcopenia is a major public health problem. Several possible mechanisms for age-related muscle atrophy have been described; however the precise contribution of each is unknown. Age-related muscle loss is thought to be a multi-factoral process composed of events such as physical activity, nutritional intake, oxidative stress, inflammatory insults and hormonal changes. There is a need for a greater understanding of the loss of muscle mass with age as this could have a dramatic impact on the elderly and critically ill if this research leads to maintenance or improvement in functional ability. This review aims to outline the process of skeletal muscle degeneration with ageing, normal and aberrant skeletal muscle regeneration, and to address recent research on the effects of gender and sex steroid hormones during the process of age-related muscle loss.     

A Vicious Cycle of Osteosarcopenia in Inflammatory Bowel Diseases—Aetiology,Clinical Implications and Therapeutic Perspectives

Sarcopenia is a disorder characterized by a loss of muscle mass which leads to the reduction of muscle strength and a decrease in the quality and quantity of muscle. It was previously thought that sarcopenia was specific to ageing. However, sarcopenia may affect patients suffering from chronic diseases throughout their entire lives. A decreased mass of muscle and bone is common among patients with inflammatory bowel disease (IBD). Since sarcopenia and osteoporosis are closely linked, they should be diagnosed as mutual consequences of IBD. Additionally, multidirectional treatment of sarcopenia and osteoporosis including nutrition, physical activity, and pharmacotherapy should include both disorders, referred to as osteosarcopenia.     

Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia

Sarcopenia, the age-associated loss of skeletal muscle mass and function, has considerable societal consequences for the development of frailty, disability, and health care planning. A group of geriatricians and scientists from academia and industry met in Rome, Italy, on November 18, 2009, to arrive at a consensus definition of sarcopenia. The current consensus definition was approved unanimously by the meeting participants and is as follows: Sarcopenia is defined as the age-associated loss of skeletal muscle mass and function. The causes of sarcopenia are multifactorial and can include disuse, altered endocrine function, chronic diseases, inflammation, insulin resistance, and nutritional deficiencies. Although cachexia may be a component of sarcopenia, the 2 conditions are not the same. The diagnosis of sarcopenia should be considered in all older patients who present with observed declines in physical function, strength, or overall health. Sarcopenia should specifically be considered in patients who are bedridden, cannot independently rise from a chair, or who have a measured gait speed less that 1 m/s(-1). Patients who meet these criteria should further undergo body composition assessment using dual energy x-ray absorptiometry with sarcopenia being defined using currently validated definitions. A diagnosis of sarcopenia is consistent with a gait speed of less than 1 m·s(-1) and an objectively measured low muscle mass (eg, appendicular mass relative to ht(2) that is ≤ 7.23 kg/m(2) in men and ≤ 5.67 kg/m(2) in women). Sarcopenia is a highly prevalent condition in older persons that leads to disability, hospitalization, and death.     

Longitudinal partially ordered data analysis for preclinical sarcopenia

Sarcopenia is a geriatric syndrome characterized by significant loss of muscle mass. Based on a commonly used definition of the condition that involves three measurements, different subclinical and clinical states of sarcopenia are formed. These states constitute a partially ordered set (poset). This article focuses on the analysis of longitudinal poset in the context of sarcopenia. We propose an extension of the generalized linear mixed model and a recoding scheme for poset analysis such that two submodels—one for ordered categories and one for nominal categories—that include common random effects can be jointly estimated. The new poset model postulates random effects conceptualized as latent variables that represent an underlying construct of interest, that is, susceptibility to sarcopenia over time. We demonstrate how information can be gleaned from nominal sarcopenic states for strengthening statistical inference on a person's susceptibility to sarcopenia.     

Extra Virgin Olive Oil (EVOO), a Mediterranean Diet Component,in the Management of Muscle Mass and Function Preservation

Aging results in a progressive decline in skeletal muscle mass, strength and function, a condition known as sarcopenia. This pathological condition is due to multifactorial processes including physical inactivity, inflammation, oxidative stress, hormonal changes, and nutritional intake. Physical therapy remains the standard approach to treat sarcopenia, although some interventions based on dietary supplementation are in clinical development. In this context, thanks to its known anti-inflammatory and antioxidative properties, there is great interest in using extra virgin olive oil (EVOO) supplementation to promote muscle mass and health in sarcopenic patients. To date, the molecular mechanisms responsible for the pathological changes associated with sarcopenia remain undefined; however, a complete understanding of the signaling pathways that regulate skeletal muscle protein synthesis and their behavior during sarcopenia appears vital for defining how EVOO might attenuate muscle wasting during aging. This review highlights the main molecular players that control skeletal muscle mass, with particular regard to sarcopenia, and discusses, based on the more recent findings, the potential of EVOO in delaying/preventing loss of muscle mass and function, with the aim of stimulating further research to assess dietary supplementation with EVOO as an approach to prevent or delay sarcopenia in aging individuals.     

Anorexia, body composition, and ageing

Over the lifespan there is a decline in food intake. This has been termed the physiological anorexia of aging. It has many causes, including alterations in the gastrointestinal satiating system, the effect of elevated leptin levels, especially in men, and a variety of changes in central nervous system neurotransmitters. Beyond the age of 70 years body mass declines. This includes both loss of adipose tissue and muscle mass. The loss of muscle mass in older individuals is termed sarcopenia. There is increasing evidence that this is caused, in men, partly by the decline in testosterone. Illness results in an increase of cytokines that produce both anorexia and cause protein wasting. Many of the causes of cachexia in older individuals are treatable. Depression is the most common cause of weight loss in older individuals. Dieting in older individuals is associated with a loss of skeletal tissue as well as fat mass. This can place older individuals at risk of becoming the 'fat frail'.     

Metabolic Syndrome and Sarcopenia

Skeletal muscle is a major organ of insulin-induced glucose metabolism. In addition, loss of muscle mass is closely linked to insulin resistance (IR) and metabolic syndrome (Met-S). Skeletal muscle loss and accumulation of intramuscular fat are associated with a variety of pathologies through a combination of factors, including oxidative stress, inflammatory cytokines, mitochondrial dysfunction, IR, and inactivity. Sarcopenia, defined by a loss of muscle mass and a decline in muscle quality and muscle function, is common in the elderly and is also often seen in patients with acute or chronic muscle-wasting diseases. The relationship between Met-S and sarcopenia has been attracting a great deal of attention these days. Persistent inflammation, fat deposition, and IR are thought to play a complex role in the association between Met-S and sarcopenia. Met-S and sarcopenia adversely affect QOL and contribute to increased frailty, weakness, dependence, and morbidity and mortality. Patients with Met-S and sarcopenia at the same time have a higher risk of several adverse health events than those with either Met-S or sarcopenia. Met-S can also be associated with sarcopenic obesity. In this review, the relationship between Met-S and sarcopenia will be outlined from the viewpoints of molecular mechanism and clinical impact.     

Frequency and Characteristics of Overestimated Renal Function in Japanese Patients with Chronic Liver Disease and Its Relation to Sarcopenia

Renal dysfunction and sarcopenia are important prognostic factors in patients with chronic liver disease (CLD). Muscle atrophy can cause the overestimation of renal function based on serum creatinine. However, the frequency of overestimated renal function in Japanese patients with CLD and its relationship with sarcopenia are unclear. In present study, we evaluated the frequency of overestimated renal function, defined as a >20% higher eGFR using creatinine than using cystatin C, in 307 patients with CLD as well as its relationship with indicators of sarcopenia. In total, 24.8% of patients had overestimated renal function. In a multivariate regression analysis, liver cirrhosis (p = 0.004) and psoas muscle mass index (p = 0.049) were significantly associated with overestimated renal function. Loss of skeletal muscle mass was significantly more frequent in both male and female patients with overestimated renal function than without. In males, the loss of muscle strength and rate of sarcopenia, defined as loss of muscle mass and strength, were significantly higher in patients with than without overestimated renal function. The high frequency of overestimated renal function in Japanese patients suggests that indicators of renal function should be carefully considered; furthermore, monitoring and interventions for both renal function and sarcopenia are needed in patients with CLD.     

Sarcopenie, fonction musculaire et prevention

Ageing is associated with sarcopenia that is characterised by loss of muscle mass and strength. Multiple factors underlie this process. Loss of motoneurons and decrease of myofibrillar protein synthesis appear to be major contributing factors. The role of other factors as decreased anabolic hormone production, mitochondrial DNA alteration, or inflammatory mediators remain to be more clearly defined. The influence of sarcopenia on disability and events as falls in the elderly is now well established. Resistance exercise programs have clearly shown benefits to potentially reverse sarcopenia. However the lack of motivation remain a limiting factor to generalize those programs especially in frail elderly. Proteino caloric intake play a major role in the prevention of sarcopenia.     

Interventions for Treating Sarcopenia: A Systematic Review and Meta-Analysis of Randomized Controlled Studies

Background

Much interest has been focused on interventions for treating sarcopenia; however, the effects have gained little evidence.

Epidemiology and consequences of sarcopenia

Sarcopenia is an evolving concept and the current definition of sarcopenia includes both a loss of muscle strength and loss of muscle mass. However, despite the increasing knowledge and improved technology, a worldwide operational definition of sarcopenia applicable across racial/ethnic groups and populations lacks consensus. As a result the prevalence of sarcopenia (8 to 40% of older people over 60 years) varies depending on the study sample (namely the age of the sample), the definition, and the assessment tool used. DXA is the main assessment method used to evaluate muscle mass, which is further adjusted to height, weight fat mass, or BMI to obtain an index of sarcopenia. Cross-sectional analyses seemed to prove an association between low muscle mass and functional decline, but these results were not consistent when analysed longitudinally over time. This inconsistency could be due to methodological issues as the selected populations in the cohorts where autonomous, community-dwelling, older people. In this highly active population decreases in muscle mass might be not as important as decreases in strength to predict functional decline. The aim of the present paper was to perform a comprehensive review of the literature on the epidemiology of sarcopenia and its consequences to be presented on November 13th and 14th 2008, at the Carla Workshop.