Table 1.
Summary depicting overlapping physiological and functional responses to Klotho expression and exercise/physical activity.
| Age-related phenotype | Klotho | Exercise |
|---|---|---|
| Gait function | Positive association: gait dysfunction observed in Kl mice; in humans, higher klotho levels are associated with improved scores on tests of lower extremity strength and functioning (Kuro-o et al., 1997; Crasto et al., 2012) | Positive association: improved fitness is associated with greater walking capacity (Peeters and Mets, 1996; Newman et al., 2006; Simonsick et al., 2006) |
| Cardiovascular disease (CVD) | Negative association: Kl mice demonstrate arteriosclerosis (Kuro-o et al., 1997). In humans, higher klotho levels were associated with lower likelihood of CVD (Semba et al., 2011) | Negative association: sedentary behavior is positively associated with mortality and CVD (Matthews et al., 2008; Warren et al., 2010; Chomistek et al., 2013) |
| Osteoporosis | Negative association: decreased Klotho levels are associated with decreased bone mineral density of hindlimb bones, primarily as a result of decreased cortical bone thickness (Kuro-o et al., 1997) | Negative association: lower physical activity is associated with decreased bone mineral density (Martyn-St James and Carroll, 2009; Hamilton et al., 2010) |
| Cognitive function | Positive association: Kl mice display impaired novel-object recognition and associative memory (Nagai et al., 2003; Kuang et al., 2014). Klotho levels have been shown to be lower in those with Alzheimer's disease (Semba et al., 2014) | Positive association: exercise promotes brain plasticity and has been shown to halt, delay and/or reverse the effects of aging on cognitive function (reviewed in Foster et al., 2011) |
| Angiogenesis | Positive association: Kl mice demonstrate significantly decreased skeletal muscle capillary density and evidence of angiogenesis following an ischemic injury (Fukino et al., 2002; Shimada et al., 2004) | Positive association: muscle loading results in a significantly increased skeletal muscle capillary density and the promotion of angiogenesis (Hoier et al., 2012) |
| Resistance to stress | Positive association: Klotho protects cells from apoptosis induced by oxidative stress (Yamamoto et al., 2005) | Positive association: whereas acute stress may induce oxidative stress and reactive oxygen species accumulation, chronic training has been shown to promote upregulation of antioxidants (Gomez-Cabrera et al., 2008; Mangner et al., 2013) |
| Tissue regeneration | Positive association: Kl mice display increase Wnt signaling, decreased stem cell numbers and an impaired regenerative response (Liu et al., 2007) | Positive association: muscle loading enhances the participation of stem cells in muscle regeneration (Ambrosio et al., 2010; Distefano et al., 2013). An acute bout of exercise results in increased satellite cell number (Dreyer et al., 2006; Kosek et al., 2006; Cermak et al., 2012), while chronic, repeated bouts mRNA expression of myogenic markers and reduces mRNA expression for inhibitors of myogenesis (Carey, 2007; Costa et al., 2007). Endurance exercise increases satellite cell content by 30–58% (Charifi et al., 2003; Verney et al., 2008) |