Sarcopenia

Molecular, Cellular, and Nutritional Aspects

Dominique Meynial-Denis, Dominique Meynial-Denis

• Publisher: CRC Press
• Year: 2019
• ISBN:
  9780429531972
• Edition: 1
• Topic: Medicina
• Subtopic: Enfermedades y alergias

Sarcopenia: Molecular, Cellular, and Nutritional Aspects describes the progressive loss of skeletal muscle mass and strength, defined by Rosenberg in 1997 as a hallmark of aging and referred to as "sarcopenia." As life expectancy continues to increase worldwide, sarcopenia has become a major public health issue. The condition worsens in the presence of chronic diseases accelerating its progression. Sarcopenia is not considered to be "a process of normative aging" but according to the International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM), as a disease. As sarcopenia is an ineluctable process, prevention and management are the only options to promote healthy aging; these actions should perhaps be taken during youth.

Included in this book:

· Features essential information on sarcopenia, its current definition, and molecular and cellular aspects of this disease

· Discusses the development of physical frailty, a complication of sarcopenia, and predicts its occurrence in the older population

· Presents alterations in muscle protein turnover and mitochondrial dysfunction in the aging process

· Provides data on the negative involvement of sarcopenia in certain chronic diseases

· Describes presbyphagia or age-related changes in the swallowing mechanism in older people

· Details possible strategies to combat muscle wasting in healthy older adults and their limits

This book features information collected from pioneers or experts on human aging from around the globe, including Europe, Brazil, Canada, Japan and the United States. It is a valuable source of information for nutritional scientists, medical doctors, sports scientists, food scientists, dietitians, students in these fields, and for anyone interested in nutrition. We hope this book provides a better understanding of sarcopenia which inevitably occurs with aging without weight loss. Moreover, this book will supply information outlining strategies to prevent or limit muscle wasting due to normal aging in order to promote successful aging.

Section VI

Applications

Part 1: Muscle Impairments or Diseases due to the Frailty Induced by Sarcopenia

16	Declines in Whole Muscle Function with Aging The Role of Age-Related Alterations in Contractile Properties of Single Skeletal Muscle Fibers Nicole Mazara and Geoffrey A. Power

CONTENTS

16.1 Introduction: Background and Impact of Sarcopenia

16.2 Muscle Morphology

16.2.1 Fiber Type and Myosin Heavy Chain Expression

16.2.2 Fiber Size and Myofibrillar Content

16.3 Isometric and Kinetic Measures of Contractile Properties

16.3.1 Single Muscle Fiber Force

16.3.2 Single Muscle Fiber Shortening Velocity

16.3.3 Single Muscle Fiber Power

16.4 Molecular Mechanisms of Contractile Properties

16.4.1 Cross-bridge Mechanics

16.4.2 Cross-bridge Bound State

16.4.3 Calcium Regulation

16.5 Whole Muscle versus Cellular Factors

16.6 Conclusion

References

16.1 INTRODUCTION: BACKGROUND AND IMPACT OF SARCOPENIA

The biological process of natural adult aging results in a gradual deterioration of the structure and function of the human neuromuscular system that accelerates into very old age (Vandervoort, 2002). The integrity of our cells, regrowth, regeneration, and neural processes are all compromised with aging, and one of the major areas impacted is skeletal muscle. However, it was not until the late 1980s that the marked reductions in skeletal muscle mass in the elderly became an area of concern for Dr. Irwin Rosenberg, who suggested that the age-associated loss of skeletal muscle mass be termed sarcopenia (literally translating into a poverty of flesh) so as to bring attention to this process (Rosenberg, 1997). Since the classification of sarcopenia, a myriad of causes for the loss of muscle mass over the lifespan have been researched, and as a result, a number of terms have emerged (Muscaratoli et al. 2010). The loss of skeletal muscle mass caused by an underlying disease-driven process—usually cancer—has been termed cachexia (Muscaritoli et al. 2010). Moreover, the terms myopenia, the loss of skeletal muscle mass or “muscle wasting” (Fearon et al. 2011), and dynapenia, the loss of muscle strength (Clark & Manini, 2008), have come into the literature as an effort to better describe and differentiate the alterations in skeletal muscle function (i.e., mass, strength, power, endurance capacity) across various populations. For the purpose of this book chapter, the term sarcopenia will refer to the age-related declines in skeletal muscle mass. Whole muscle function will refer to muscle mass, strength, power, and endurance capacity.

At approximately 60 years of age, the rate of skeletal muscle mass loss becomes appreciable (i.e., the onset of the sarcopenia process) and is estimated at ~1%–2% per year, and the associated rate of skeletal muscle strength loss is higher, estimated to be ~3% per year (von Haehling et al. 2010). While the process of sarcopenia affects all older adults, the state of being “sarcopenic” or “frail” has specific diagnostic criteria (Muscaritoli et al. 2010), and the sarcopenic phenotype is often accompanied by muscle weakness, increased fatigability (Power et al. 2013), and/or performance deficits (Muscaritoli et al. 2010; Cruz-Jentoft et al. 2010). On average, it is estimated that ~35% of older adults have diagnosable sarcopenia, and those sarcopenic older adults have an increased risk of falls, fractures, impaired mobility, frailty, metabolic dysfunction (such as type 2 diabetes), and overall lower quality of life (von Haehling et al. 2010).

There is a limited understanding regarding the etiology of sarcopenia, rendering the development of effective treatments limited, and explaining why even active older adults suffer from the sarcopenia process. The progression of sarcopenia has been linked to reorganization of the motor neuron and associated innervation (Deschenes et al. 2010), loss of motor units (Dalton et al. 2010; McNeil et al. 2005; Power et al. 2012), neuromuscular junction degeneration (Jang et al. 2010), mitochondrial dysfunction (Gouspillou et al. 2018; Marzetti et al. 2013), irreversible oxidation damage (Brocca et al. 2017; Jackson & McArdle 2011), and reductions in muscle protein synthesis rates in response to anabolic stimuli (Leenders et al. 2011). Alterations in cellular muscle mechanics, such as the disruption of force-producing characteristics, cross-bridge cycling, and calcium (Ca²⁺) release and sensitivity, have also been found in aging muscle and could offer another explanation for the seemingly inevitable onset and progression of sarcopenia in healthy adult aging skeletal muscle. The investigation of the role of cellular and molecular mechanisms driving impaired performance of skeletal muscle is vital to the understanding of how sarcopenia impacts the age-related alterations in whole muscle function.

This chapter will discuss:

• The changes in muscle morphology with aging and the association with sarcopenia.

• The testing and quantification of single muscle fiber mechanics.

• The mechanisms underpinning single muscle fiber mechanics.

• How cellular mechanics change with aging and contribute to sarcopenia.

16.2 MUSCLE MORPHOLOGY

Skeletal muscle generates the contractile force necessary to support multiple forms of locomotion, from the explosive power of a jump to the fine motor skill of knitting. In order to enable the execution of these distinctly differe nt physical functions, skeletal muscles exhibit different morphological/architectural features such as pennation angle, fascicle length, muscle length, and muscle fiber innervation (i.e., fast or slow twitch motor units). Similar to whole muscle structure, properties of the muscle cell, such as fiber type and size, fit to match the physical demands of the muscle.

16.2.1 FIBER TYPE AND MYOSIN HEAVY CHAIN EXPRESSION

A motor unit, consisting of the motor neuron and muscle fibers it innervates, can be divided generally into two different types: slow twitch and fast twitch; the fibers of which commonly express myosin heavy chain (MHC) I and II isoforms, respectively. Type I (TI) fibers are generally recruited for low-force producing, repetitive, and accuracy-based tasks, whereas type II (TII) fibers are recruited for high-force producing and more powerful tasks. MHC isoform expression is a commonly used technique to identify fiber type, and it has been shown that MHC expression correlates well with contractile properties of single muscle fibers in young adults (Aagaard & Andersen 1998; Bottinelli et al. 1996, 1999; Harridge et al. 1996). There are three primary MHC isoforms in adult human muscle. MHC I expressing fibers are typically smaller, weaker, slower, and more fatigue resistant (i.e., higher endurance capacity) (Larsson & Moss 1993; Bottinelli et al. 1996) across the three fiber types. Fibers that express MHC IIA are typically larger, faster, stronger, more powerful, and fatigue more quickly than MHC I. There is a small proportion of adult fibers that express MHC IIX, and these fibers are typically very powerful, produce force very quickly, and fatigue the fastest of the three fiber types (Larsson & Moss 1993; Bottinelli et al. 1996). Fibers can also co-express MHC isoforms and are referred to as hybrid fibers; these fibers are common in models of disuse atrophy (Gallagher et al. 2005; Ohira et al. 1999). Hybrid fibers show mixed contractile properties associated with the isoforms being expressed and occur in young, healthy adult muscle in low proportions (Bottinelli et al. 1996).

Age-related changes in fiber type distribution and MHC expression are muscle and species dependent. In a large, cross-sectional study across the ages of 15–83 years, it was determined that the driving force behind whole muscle mass loss with age (i.e., sarcopenia) was a loss of muscle fibers, specifically TII fibers, while TI fibers seemed to remain intact over a lifespan (Lexell et al. 1988). A loss, or lower proportion of, TII/MHC IIA containing fibers with aging has been found in other studies as well (Larsson et al. 1978; Oh et al. 2018; Trappe et al. 1995). The loss of TII fibers with aging can happen as a result of denervation, which either leads to atrophy and cell death or reinnervation by a neighboring motor unit. As reinnervation seems to cause fibers to co-express MHC isoforms (Purves-Smith et al. 2014; Rowan et al. 2012), it is likely that some TII fibers are not “lost” but are changing classification through reinnervation. This is supported in both humans and rodent models where the proportion of hybrid fibers is greater with aging (Andersen et al. 1999; Edstrom & Ulfhake 2005; Klitgaard et al. 1990; Monemi et al. 1999; Rowan et al. 2012). Another characteristic of denervated fibers is the highly angular shape, different from the typical cylindrical shape of muscle fibers, and angular muscle fibers have been found in aging humans (Andersen 2003; Power et al. 2016) and rodent models (Rowan et al. 2011, 2012). The denervation–reinnervation process is a major contributor to the loss of muscle fibers, expressing any MHC isoform, and progression of sarcopenia.

Sarcopenia, being the age-associated loss of muscle mass, is often confounded by disuse. Many older adults become less physically active and are at greater risk of a mobility-limiting injury or illness. Disuse has been shown to cause atrophy and fiber loss (Rowan et al. 2011) and seems to affect TI fibers, conversely to the TII-targeted process of aging (D’Antona et al. 2003; Hortobagyi et al. 2000; Widrick et al. 1999). As aging is often accompanied by disuse, this phenomenon causes fiber type distribution alterations to be unclear in the context of healthy aging compared with disuse atrophy, and how the two interact.

Alterations in MHC isoform expression are likely a symptom of the denervation–reinnervation process that occurs when motor units are lost during aging, and over longitudinal studies, tracking MHC isoform expression of single muscle fibers is a useful tool in quantifying age-related changes in muscle quality.

16.2.2 FIBER SIZE AND MYOFIBRILLAR CONTENT

Muscle fiber size is measured as cross-sectional area (CSA) either via diameter and depth measurements of single muscle fibers or area measurements of stained muscle cross-sections. Similar to fiber type distribution, there is evidence that TII fibers are preferentially targeted and atrophy more than TI fibers. It was found that TII fiber size was ~25% smaller in the old as compared with the young group (Lexell et al. 1988). Many studies are in agreement with the above findings from stained muscle cross-sections that TII fibers have a smaller CSA than TI in old compared with young adults (Aniansson et al. 1986; Coggan et al. 1992; Jennekens et al. 1971). A recent study found that older men had smaller TII muscle fiber CSA compared with TI fiber CSA (Snijders et al. 2016), and a study from the same group found a significant reduction in TII muscle fiber CSA between young and older men, but no difference in TI CSA (Nederveen et al. 2016).

However, in a longitudinal study, it was noted that fiber area for all types increased between the ages of 76–80 years suggesting that a “compensatory hypertrophy” was occurring in the fibers causing an increase in fiber size at a critical point in the aging process at about 75 years (Aniansson et al. 1992). This compensatory mechanism is likely associated with the ...