Osteoprotegrin (OPG) as a therapeutic target to combat age associated muscle loss.

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BackgroundOsteoprotegerin (OPG) is a circulating factor more commonly associated with the regulation of bone resorption. OPG acts as a decoy receptor to the ligand of the RANK molecule (RANKL). The proportion of RANKL to OPG must remain balanced to maintain bone turnover (Grimaud et al., 2003 Kong et al., 1999; Lacey et al., 1998); OPG is released when RANKL levels are elevated, ensuring bone resorption does not continually occur when RANK/RANKL are bound. OPG is also released from muscle in murine models of degenerative diseases. However, the specific pathway that causes these changes has not been identified (Shen et al., 2017; Dufresne et al., 2016a; Dufresne et al., 2016b; Dufresne et al., 2015). The Impact of Osteoprotegerin in AgeingAfter the age of 50 years old, muscle mass declines by 1-2% per year, with a total decline of ~25% between the ages of 50 and 75 years (Delmonico et al., 2009; Marcell, 2003; LaPier, 1997; Waters et al., 2008). The most recent definition of sarcopenia includes three key parameters; low levels of muscle strength, muscle quality/quantity and physical performance. Muscle quality and quantity are the primary indicators of probable sarcopenia (Cruz-Jentoft et al., 2018). Early diagnosis and treatment of sarcopenia is essential to mitigate the high personal, social and economic burdens that it becomes associated with when left untreated (Cruz-Jentoft et al., 2018).