Context-Dependent Regulation of Autophagy by IKK-NF-κB Signaling : Impact on the Aging Process

Abstract EN

The NF-κB signaling system and the autophagic degradation pathway are crucial cellular survival mechanisms, both being well conserved during evolution.

Emerging studies have indicated that the IKK/NF-κB signaling axis regulates autophagy in a context-dependent manner.

IKK complex and NF-κB can enhance the expression of Beclin 1 and other autophagy-related proteins and stimulate autophagy whereas as a feedback response, autophagy can degrade IKK components.

Moreover, NF-κB signaling activates the expression of autophagy inhibitors (e.g., A20 and Bcl-2/xL) and represses the activators of autophagy (BNIP3, JNK1, and ROS).

Several studies have indicated that NF-κB signaling is enhanced both during aging and cellular senescence, inducing a proinflammatory phenotype.

The aging process is also associated with a decline in autophagic degradation.

It seems that the activity of Beclin 1 initiation complex could be impaired with aging, since the expression of Beclin 1 decreases as does the activity of type III PI3K.

On the other hand, the expression of inhibitory Bcl-2/xL proteins increases with aging.

We will review the recent literature on the control mechanisms of autophagy through IKK/NF-κB signaling and emphasize that NF-κB signaling could be a potent repressor of autophagy with ageing.