Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator 
of energy metabolic homeostasis and thus a major survival factor in a variety of 
metabolic stresses and also in the aging process. Metabolic syndrome is 
associated with a low-grade, chronic inflammation, primarily in adipose tissue. 
A low-level of inflammation is also present in the aging process. There are 
emerging results indicating that AMPK signaling can inhibit the inflammatory 
responses induced by the nuclear factor-κB (NF-κB) system. The NF-κB subunits 
are not direct phosphorylation targets of AMPK, but the inhibition of NF-κB 
signaling is mediated by several downstream targets of AMPK, e.g., SIRT1, 
PGC-1α, p53, and Forkhead box O (FoxO) factors. AMPK signaling seems to enhance 
energy metabolism while it can repress inflammatory responses linked to chronic 
stress, e.g., in nutritional overload and during the aging process. AMPK can 
inhibit endoplasmic reticulum and oxidative stresses which are involved in 
metabolic disorders and the aging process. Interestingly, many target proteins 
of AMPK are so-called longevity factors, e.g., SIRT1, p53, and FoxOs, which not 
only can increase the stress resistance and extend the lifespan of many 
organisms but also inhibit the inflammatory responses. The activation capacity 
of AMPK declines in metabolic stress and with aging which could augment the 
metabolic diseases and accelerate the aging process. We will review the AMPK 
pathways involved in the inhibition of NF-κB signaling and suppression of 
inflammation. We also emphasize that the capacity of AMPK to repress 
inflammatory responses can have a significant impact on both healthspan and 
lifespan.