skeletal muscles of young mice whereas in old rats no stimulation was apparent. In addition, Liu et al. [122] demonstrated in a mouse model that stroke induced a major activation of AMPK in young animals but no response occurred in their older counterparts. These studies and many other observations indicate that the aging process impairs the activation capacity of AMPK signaling and in that way, disturbs autophagic activity, evokes oxidative stress and triggers the activation of inflammasomes. Moreover, AMPK activity represses NF-κB signaling [123] which could suppress the priming of inflammasomes in young animals but this effect may be lost during aging. There are several pharmacological activators of AMPK, e.g. AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) and the clinically-used antidiabetic drug metformin [105]. Both of these compounds also have AMPK-independent effects. AICAR stimulates AMPK-dependent autophagy via ULK1 and FoxO3a [124,125]. Several natural products, e.g. berberine, curcumin and quercetin, have been reported to activate AMPK signaling [105].
