NF-κB, a culprit of both inflamm-ageing and declining immunity?

Abstract

NF-κB is generally recognized as an important regulator of ageing, through its roles in cellular senescence and inflammatory pathways. 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 inflamm-ageing 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. Here, we discuss some areas where further research may bear fruit in our understanding the impact of NF-κB in healthy ageing and longevity.

A Data-Mining Approach to Identify NF-kB-Responsive microRNAs in Tissues Involved in Inflammatory Processes: Potential Relevance in Age-Related Diseases

“…Inflammaging, which is principally sustained by the activation of the innate immune cells, is paralleled by the increased burden of senescent cells acquiring a senescence-associated secretory phenotype (SASP), which turns senescent cells into proinflammatory cells [ 86 , 93 , 94 , 95 , 96 ]. In immune cells and tissues obtained from patients affected by the most common ARDs, NF-kB is commonly constitutively activated [ 97 ]. Of note, NF-kB activation should be an inducible, but transient, event in physiological conditions.…”

COVID-19 mRNA Vaccine Effectiveness against Elderly Frail People

“…“Inflamm-ageing” is a systemic multifactorial condition, characterized by complex interactions owing to an excess of molecular mediators, as exemplified by the nuclear factor (NF)-κB interactome. NF-κB appears to influence the age-linked deficiencies of innate and adaptive immune systems, related to “inflamm-ageing” (mediated principally by the innate immune arm) and diminishing adaptive immunity (via inherent deficiencies of lymphocytes in signaling and proliferation), respectively [ 5 ].…”

Single-molecule tracking reveals two low-mobility states for chromatin and transcriptional regulators within the nucleus

“…To test this hypothesis, we performed SMT experiments and subsequent analysis on several nuclear proteins with different functions. RELA/p65 is an important subunit of the NF-kB transcription factor, which is activated in response to many external stimuli (35). Glucocorticoid receptor-interacting protein 1 (GRIP1), also known as nuclear receptor coactivator 2 (NCoA2) is a coregulatory protein that is recruited to DNA by nuclear receptors in response to ligand-activation (36).…”