Sarcopenia was originally defined as the age-related loss of\u00a0muscle mass. Subsequently, it became obvious to\u00a0clinicians that it was muscle quality, rather than muscle\u00a0mass that determined the function of muscle. This led\u00a0to the suggestion that it was muscle power (force x\u00a0velocity) which should be utilized to determine the role of
\nmuscle in determining outcomes. It was suggested that this\u00a0should be termed dynapenia. From this developed the\u00a0concept of a sarcopenia-disability cascade. Each\u00a0component of this cascade can be separately measured and\u00a0theoretically would lead to worse outcomes.<\/p>\n
However, in 2010, Cruz-Jentoft et al. published the\u00a0\u2018\u2018European Consensus on Definition and Diagnosis of\u00a0Sarcopenia.\u2019\u2019 They redefined sarcopenia as being muscle\u00a0loss coupled with a decline in function (either walking\u00a0speed or grip strength). This definition was validated as\u00a0having a strong predictive ability of poor outcomes.\u00a0Subsequently, 4 other definitions of sarcopenia, all using\u00a0gait speed and grip strength, as well as some measurement\u00a0of low muscle mass have been published. Each uses\u00a0slightly different cut off points and 2 recognized the\u00a0importance of having different cut offs for different ethnic\u00a0groups. Woo et al. compared each of these definitions\u00a0and found that they had slightly different predictive abilities. Of the definitions, the Foundation of NIH (FNIH)\u00a0sarcopenia criteria using gait speed, but not grip strength,\u00a0had slightly better predictive value for poor outcomes.<\/p>\n
Based on the parallels between osteoporosis and sarcopenia and the finding that the 6 FRAX questions\u00a0without Bone Mineral Density are highly predictive of\u00a0fracture risk, we developed a simple sarcopenic\u00a0questionnaire to predict poor muscle function. This questionnaire has been shown to be a valid\u00a0predictor of poor outcomes similar to that of the FNIH\u00a0(walking speed) definition in both the United States and\u00a0Asia.<\/p>\n
Sarcopenia has multiple causes and, as older persons\u00a0develop a variety of diseases with increased production of\u00a0cytokines, it may overlap with cachexia. In this review, we will first explore the physiological causes of\u00a0sarcopenia with a special emphasis\u00a0on potential pharmaceutical targets. We will then review the available and\u00a0developing treatments for sarcopenia.<\/p>\n
The Pathophysiology of Sarcopenia\u00a0When muscle contracts this activates mechanoreceptors,\u00a0i.e., titin and dystroglycan, and causes muscle injury. The\u00a0mechanoreceptors increase the activity of muscle growth\u00a0factors (IGF1-Ea and muscle growth factor) which increase\u00a0muscle protein synthesis and recruit satellite cells and\u00a0motor units. This leads to muscle regeneration and\u00a0increased muscle function. With aging, there is\u00a0increased muscle injury with a decrease in muscle regeneration and function. This is due to a decrease in muscle\u00a0growth factors leading to a reduction in the protein synthesis\/degradation cycle and the activation of satellite cells\u00a0and motor units. Anatomically, with aging there is Type II\u00a0fiber atrophy resulting in decreased muscle mass, strength,\u00a0and power.<\/p>\n
Old muscle shows fiber size heterogeneity and fiber\u00a0grouping with an increase in myosin heavy chain. This\u00a0differs from cachexia where fiber size variability is not\u00a0seen. This is similar to the histological changes seen with\u00a0Amyotrophic Lateral Sclerosis. Sarcopenic patients have a\u00a0reduction in the motor unit number index (MUNIX) which\u00a0is intermediate between that seen in healthy older persons\u00a0and in patients with Amyotropic Lateral Sclerosis.\u00a0Further evidence of motor neuron degeneration is the increase in C-terminal agrin fragments in about a third of\u00a0sarcopenic patients. With aging, there is a 25 % loss of\u00a0motoneurons leading to sprouting of small motor neurons that innervate Type II fibers leading to an eventual loss\u00a0of type II fibers. Circulating levels of ciliary neurotopic factor (CNTF), which stimulate motor unit formation, decline with aging. Older persons who\u00a0have the null allele rs1800169 for CNTF have lower grip\u00a0strength. Axokine, a modified version of CNTF, was\u00a0tried for weight loss due to its anorectic properties. The\u00a0trials were suspended when subjects developed antibodies\u00a0to CNTF.<\/p>\n
<\/p>\n
Morley, John E. “Pharmacologic options for the treatment of sarcopenia.” Calcified tissue international<\/i> 98.4 (2016): 319-333.<\/p>\n","protected":false},"excerpt":{"rendered":"
Sarcopenia was originally defined as the age-related loss of\u00a0muscle mass. Subsequently, it became obvious to\u00a0clinicians that it was muscle quality, rather than muscle\u00a0mass that determined the function of muscle. This […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[181],"tags":[414],"_links":{"self":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/621"}],"collection":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/comments?post=621"}],"version-history":[{"count":1,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/621\/revisions"}],"predecessor-version":[{"id":622,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/621\/revisions\/622"}],"wp:attachment":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/media?parent=621"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/categories?post=621"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/tags?post=621"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}