NF-κB in Age-Related Inflammation and Immunosenescence

NF-κB is a well studied player in the complex regulatory systems that control the production and processing of inflammatory signaling in cells. Cells sense their environment and produce inflammatory signals in reaction to prompts, drawing in immune cells to investigate and amplify the local response if necessary. Unfortunately the cell and tissue damage characteristic of aging triggers cells into producing inflammatory signals. The consequent chronic inflammation is disruptive of tissue function throughout the body, contributing to degenerative aging. Sophisticated control over inflammatory signaling, eliminating excess inflammation while allowing necessary inflammatory signaling to proceed, is thus an important goal in the treatment of aging.

It is important to identify connections between seemingly unrelated mechanisms of ageing, or to discover new aspects of ageing biology. One of the master transcriptional regulators at the crossroads of immunity and ageing is nuclear factor kappa B (NF-κB), with its diverse roles implicated in nearly all the hallmarks of ageing. In this mini review, we aim to expose relatively unexplored topics surrounding NF-κB in the spirit of 'leave no stone unturned'. In both the innate and the adaptive immune systems, NF-κB senses danger signals and regulates the expression of cytokines and their receptors in a complex cell-cell communication cascade. Therefore, any age-related intrinsic defects of NF-κB signaling would have a direct impact on cell-cell communications within the immune system and with the surrounding microenvironments.

Here we discuss evidence and ideas for the relevance of NF-κB in two concepts of immune ageing: inflammageing and declining adaptive immunity (immunosenescence). Activated in virtually all cell-cell communication networks of the immune system, NF-κB is thought to affect age-related defects of both innate and adaptive immune cells, relevant to inflammageing and declining adaptive immunity, respectively. Moreover, the family of NF-κB proteins that exist as heterodimers and homodimers exert their function beyond the immune system. Given their involvement in diverse areas such as DNA damage to metabolism, NF-κB has the potential to serve as linkages between known hallmarks of ageing. However, the complexity of NF-κB dimer composition, dynamic signaling, and tissue-specific actions has received relatively little attention in ageing research.


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