NF-kappaB signaling in the aging process.

INTRODUCTION: The aging process represents a progressive decline in cellular and organism function. Explaining the aging process has given rise to a cornucopia for different theories in which the basic difference has been the question whether aging is genetically regulated or an entropic degeneration process.

DISCUSSION: Different screening techniques have revealed that mammalian aging is associated with the activation of NF-kappaB transcription factor system. The NF-kappaB system is an ancient host defense system concerned with immune responses and different external and internal dangers, such as oxidative and genotoxic stress. NF-kappaB signaling is not only the master regulator of inflammatory responses but can also regulate several homeostatic responses such as apoptosis, autophagy, and tissue atrophy. We will describe how chronic activation of NF-kappaB signaling has the capacity to induce the senescent phenotype associated with aging. Interestingly, several longevity genes such as SIRT1, SIRT6, and FoxOs can clearly suppress NF-kappaB signaling and in this way delay the aging process and extend lifespan.

CONCLUSION: It seems that the aging process is an entropic degeneration process driven by NF-kappaB signaling. This process can be regulated by a variety of longevity genes along with a plethora of other factors such as genetic polymorphism, immune and dietary aspects, and environmental insults.