Table 1.

Aging modulates the expression in skeletal muscle of molecules that influence muscle inflammation and regeneration.

Molecule	Species	Net change with age	Potential source in muscle	Effects on muscle regeneration	Effect on muscle inflammation	References
TNFα	human, mouse, rat	increase	macrophages, neutrophils, muscle cells, endothelial cells, fibroblasts	promotes muscle cell proliferation, inhibits myoblast differentiation, promotes protein catabolism, reduces protein synthesis rate, chemotactic recruitment of muscle cells to lesions	stimulates production of Th1 cytokines, promotes the M1 macrophage phenotype	Greiwe et al., 2001; van der Poel et al., 2011; Wang et al., 2015, 2018; Wehling-Henricks et al., 2018; Collins and Grounds, 2001; Sloboda et al., 2018; Warren et al., 2002; Li, 2003; Langen et al., 2001, 2004; Reid and Li, 2001, Lang et al., 2002; Torrente et al., 2003; Locati et al., 2003; Tidball and Villalta, 2010
IFNγ	mouse	increase	macrophages, natural killer cells, T-cells	inhibits muscle cell proliferation, inhibits muscle cell differentiation	stimulates production of Th1 cytokines, promotes the M1 macrophage phenotype, represses the M2 macrophage phenotype	Wang et al., 2015; Wehling-Henricks et al., 2018; Cheng et al., 2008; Fu et al., 2015; Panduro et al., 2018; Kalovidouris et al., 1993; Kelić et al., 1993; Londhe and Davie et al., 2011; Villalta, et al., 2011a; Mills et al., 2000; Tidball, 2017; Tidball and Villalta, 2010
IL6	human, mouse, rat	unchanged	macrophages, muscle cells	promotes muscle cell proliferation, promotes muscle cell differentiation	promotes the M2 macrophage phenotype, macrophage chemoattractant	Przybyla et al., 2006; Wang et al., 2015; Hamada et al., 2015; Visser et al., 2002; Serrano et al., 2008; Kami and Senba, 1998; Zhang et al., 2013; Hoene et al., 2013, Toth et al., 2011; Haddad et al., 2005; Chen et al., 2018, Duluc et al., 2007
IL1β	mouse, human	increase	macrophages	inhibits IGF-1-mediated differentiation of muscle cells	promotes Th1 cytokine production, macrophage chemoattractant	Przybyla et al., 2006; Wang et al., 2015; Arnold et al., 2007; Perdiguero et al., 2011, Wang et al., 2014; Broussard et al., 2004; Mortala et al., 2018; Rider et al., 2011
IL10	human, mouse	increase	macrophages, regulatory T-cells	IL-10-activated macrophages promote muscle cell proliferation, reduces M1 macrophage-mediated cytotoxicity, modulates muscle cell differentiation	deactivates the M1 macrophage phenotype, promotes the M2 macrophage phenotype	Przybyla et al., 2006; Wang et al., 2015; Deng et al., 2012; Villalta et al., 2009; Villalta et al., 2011b; Castiglioni et al., 2015; Villalta et al., 2014; Mosser and Zhang, 2008; Murray, 2016; Martinez-Pomares et al., 2003; Welc et al., 2020
GDF3	mouse	decrease (following injury)	macrophages	promotes muscle cell fusion, increases regenerating myofiber cross-sectional area	inhibits Th1 cytokine production	Patsalos et al., 2018; Varga et al., 2016; Wang et al., 2020
OPN	mouse	increase (following injury)	macrophages, muscle cells, T-cells	promotes muscle cell fusion (ECM-bound OPN), promotes muscle cell differentiation (soluble OPN), inhibits muscle cell differentiation (soluble OPN), promotes muscle regeneration	promotes Th1 cytokine production, inhibits the M2 macrophage phenotype, macrophage chemoattractant, neutrophil chemoattractant	Paliwal et al., 2012; Denhardt et al., 2001; Pereira et al., 2006; Uaesoontrachoo n et al., 2008; Wasgewatte Wijesinghe et al., 2019; Patarca et al., 1989; Hirata et al., 2003; Marcondes et al., 2008; Shi et al., 2018; Zhu et al., 2004; Koh et al., 2007; Ashkar et al., 2000; Many et al., 2016
Klotho	mouse	decrease	macrophages, muscle cells, fibro-adipogenic progenitor cells	promotes muscle cell proliferation, increases myofiber growth	promotes Th1 cytokine production, promotes Th2 cytokine production, increases M2-biased macrophage numbers	Kuro-o et al., 1997; Wehling-Henricks et al., 2016, 2018; Sahu et. al., 2018; Welc et al., 2020b; Sahu et al., 2018; Ahrens et al., 2018
IGF1	human, mouse, rat	decrease	macrophages, muscle cells	promotes muscle cell proliferation, promotes muscle cell differentiation, stimulates protein synthesis, promotes muscle fiber growth, increases aged muscle growth (exogenous administration)	promotes the M2 macrophage phenotype	Corpas et al., 1993; Kelijman, 1991; Lamberts et al., 1997; Lu et al., 2010; Tonkin et al., 2015; Jennische et al., 1987; Allen and Boxhorn, 1989; Coolican et al., 1997; Palmer et al., 1997; Barton-Davis et al., 1998