Sarcopenia was originally defined as the age-related loss of muscle mass. Subsequently, it became obvious to clinicians that it was muscle quality, rather than muscle mass that determined the function of muscle. This led to the suggestion that it was muscle power (force x velocity) which should be utilized to determine the role of
muscle in determining outcomes. It was suggested that this should be termed dynapenia. From this developed the concept of a sarcopenia-disability cascade. Each component of this cascade can be separately measured and theoretically would lead to worse outcomes.
However, in 2010, Cruz-Jentoft et al. published the ‘‘European Consensus on Definition and Diagnosis of Sarcopenia.’’ They redefined sarcopenia as being muscle loss coupled with a decline in function (either walking speed or grip strength). This definition was validated as having a strong predictive ability of poor outcomes. Subsequently, 4 other definitions of sarcopenia, all using gait speed and grip strength, as well as some measurement of low muscle mass have been published. Each uses slightly different cut off points and 2 recognized the importance of having different cut offs for different ethnic groups. Woo et al. compared each of these definitions and found that they had slightly different predictive abilities. Of the definitions, the Foundation of NIH (FNIH) sarcopenia criteria using gait speed, but not grip strength, had slightly better predictive value for poor outcomes.
Based on the parallels between osteoporosis and sarcopenia and the finding that the 6 FRAX questions without Bone Mineral Density are highly predictive of fracture risk, we developed a simple sarcopenic questionnaire to predict poor muscle function. This questionnaire has been shown to be a valid predictor of poor outcomes similar to that of the FNIH (walking speed) definition in both the United States and Asia.
Sarcopenia has multiple causes and, as older persons develop a variety of diseases with increased production of cytokines, it may overlap with cachexia. In this review, we will first explore the physiological causes of sarcopenia with a special emphasis on potential pharmaceutical targets. We will then review the available and developing treatments for sarcopenia.
The Pathophysiology of Sarcopenia When muscle contracts this activates mechanoreceptors, i.e., titin and dystroglycan, and causes muscle injury. The mechanoreceptors increase the activity of muscle growth factors (IGF1-Ea and muscle growth factor) which increase muscle protein synthesis and recruit satellite cells and motor units. This leads to muscle regeneration and increased muscle function. With aging, there is increased muscle injury with a decrease in muscle regeneration and function. This is due to a decrease in muscle growth factors leading to a reduction in the protein synthesis/degradation cycle and the activation of satellite cells and motor units. Anatomically, with aging there is Type II fiber atrophy resulting in decreased muscle mass, strength, and power.
Old muscle shows fiber size heterogeneity and fiber grouping with an increase in myosin heavy chain. This differs from cachexia where fiber size variability is not seen. This is similar to the histological changes seen with Amyotrophic Lateral Sclerosis. Sarcopenic patients have a reduction in the motor unit number index (MUNIX) which is intermediate between that seen in healthy older persons and in patients with Amyotropic Lateral Sclerosis. Further evidence of motor neuron degeneration is the increase in C-terminal agrin fragments in about a third of sarcopenic patients. With aging, there is a 25 % loss of motoneurons leading to sprouting of small motor neurons that innervate Type II fibers leading to an eventual loss of type II fibers. Circulating levels of ciliary neurotopic factor (CNTF), which stimulate motor unit formation, decline with aging. Older persons who have the null allele rs1800169 for CNTF have lower grip strength. Axokine, a modified version of CNTF, was tried for weight loss due to its anorectic properties. The trials were suspended when subjects developed antibodies to CNTF.
Morley, John E. “Pharmacologic options for the treatment of sarcopenia.” Calcified tissue international 98.4 (2016): 319-333.