The chaperoning systems that participate in controlling cellular homeostasis have been detected in skeletal muscle. Small Hsp, Hsp60, Hsp70, and Hsp90 play a significant role in muscle adaptation [
17,
127]. Nevertheless, Hsp60 was not deeply investigated after physical exercise, which, as we have already discussed, influences muscle homeostasis [
77]. Hsp60 and exercise correlation appears to be rational, but literature data are restricted and sometimes controversial (). Morton et al. [
128] demonstrated that aerobically trained men had significantly higher resting levels of Hsp60 in the vastus lateralis muscle (high percentage of fibers I and IIa) compared to untrained subjects, suggesting Hsp60 as a molecular marker of physiological adaptation to aerobic exercise. However, it has been demonstrated that in the human vastus lateralis muscle the highest mitochondrial content is showed by type I fibers followed by type IIa > IIx () [
49]. At the same time, an acute single bout of endurance training that is considered an aerobic exercise did not increase the basal Hsp60 protein levels in the same muscle [
128]. Thus, chronic training has the capacity to increase Hsp60 expression, whereas a single bout of exercise does not. Hsp60 expression is stimulated by endurance, resistance, and mixed training, but its fiber specificity is still debated. Hsp60 expression in the vastus lateralis of healthy active people with different training backgrounds was considered not to be fiber-type specific [
129]. In agreement, Ogata et al. [
130] and Soares Moura et al. [
131] did not show significant differences in Hsp60 levels in the plantaris and gastrocnemius, both rich fiber IIx muscles, of male rats after endurance training. On the other hand, several groups, including ours, demonstrated fiber-type specificity after training in specific muscles. Mattson et al. [
132] showed that female rats trained with an endurance protocol for 8 weeks displayed significantly higher levels of Hsp60 in the muscle plantaris, which is rich in fiber-type IIb [
46]. No difference of Hsp60 levels was detected in the rich fiber I muscle soleus in endurance-trained rats compared to the untrained group [
47,
132]. Hsp60 fiber-type I specificity was reported by Samelman [
133], who showed increased basal levels of Hsp60 in the soleus and not in the lateral gastrocnemius of endurance trained rats. In agreement, our group noted Hsp60 fiber-specific expression in healthy male BALB/c mice trained for 45 days on the treadmill. Specifically, higher levels of Hsp60 were observed in type I and IIa muscle fibers, while type IIx and IIb fibers showed a constitutive expression of this chaperonin [
134]. Therefore, increased levels of Hsp60 were reported after six weeks of endurance training, mainly in red gastrocnemius and soleus muscles, which are particularly rich in type I and IIa fibers [
134]. We also correlated this physiological adaptation to an increased expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), which triggers the mitochondrial biogenesis and thereby avoiding the cytotoxic effects [
134,
135,
136]. Finally, increased levels of Hsp60 were observed in the soleus muscle of male mice and the Extensor Digitorum Longus (EDL) muscle of female mice after an acute single bout of endurance training [
48].