NF-κB shows up in a range of research on longevity and aging. It's one of a number of central pieces of biological machinery that appear to be altered by methods of extending life in laboratory animals, but which influence (usually indirectly) so very many processes and mechanisms that understanding how it all fits together becomes an enormous task. In this open access paper researchers look at NF-κB in the context of the immune system failure and systematic chronic inflammation that occurs with aging:
Chronic inflammation is a major biological mechanism underpinning biological ageing process and age-related diseases. Inflammation is also the key response of host defense against pathogens and tissue injury. Current opinion sustains that during evolution the host defense and ageing process have become linked together.
An excessive activation of NF-κB signaling pathway characterizes the entropic ageing process, responsible of inflammageing and SASP phenotype, and the consequent onset of several age-related diseases. This is plausible since nearly all insults enhancing the ageing process are well-known activators of NF-κB signaling system.
Thus, the large array of defense factors and mechanisms linked to the NF-κB system seem to be involved in ageing process. This concept leads us in proposing inductors of NF-κB signaling pathway as potential ageing biomarkers. On the other hand, ageing biomarkers, represented by biological indicators and selected through apposite criteria, should help to characterize biological age and, since age is a major risk factor in many degenerative diseases, could be subsequently used to identify individuals at high risk of developing age-associated diseases or disabilities. In addition, we also suggest [these biomarkers] as targets for the development of new therapeutic strategies against ageing and age-related diseases.
In the programmed view of aging, targeting things like the NF-κB signaling pathway is the logical first step, as aging is thought by that school to be caused by changes in gene expression and behavior of signaling pathways. In the more mainstream view of aging as caused by accumulated cellular and molecular damage, however, altering gene expression and pathway behavior is only a patch on the real problem. Those changes are a reaction to various forms of molecular damage in and between cells, and changing the response to damage rather than repairing that damage is only of limited benefit. It's a little like changing the oil in your car and hoping rather than replacing worn engine components.
Unfortunately despite the fact that most of the research community supports damage-based theories of aging, scientists still largely pursue research that better fits the programmed view of aging - i.e. that seeks only to alter biological reactions to the cause of aging rather than directly addressing the damage that is the cause. Only by repairing the damage, such as by implementing the SENS proposals for rejuvenation therapies, can we create truly effective therapies for aging.