NF-κB pathway activators as potential ageing biomarkers: targets for new therapeutic strategies

Abstract

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. 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 this report, some inflammatory biomarkers will be discussed for a better understanding of the concept of biological ageing, providing ideas on eventual working hypothesis about potential targets for the development of new therapeutic strategies and improving, as consequence, the quality of life of elderly population.

Figure 1

Ageing process results by the lost of molecular fidelity followed by an improved entropy. This determines loss complexity and random accumulation of damages (i.e. particularly damages to nuclear and mitochondrial DNA) at cellular, tissue, organ levels and/or of whole body. Thus, it becomes more easily vulnerable to internal and external stressors, frailty, disability and disease.

Figure 2

NF-kB system is at the hub of aging inflammatory network Its activation is induced by different factors, such as mitochondria dysfunction, oxidative stress, activation of Inflammasomes, decline of autophagic cleansing. Other NF-kB activators are activation of innate/inflammatory responses by PAMPs and DAMPs, elevated induction of insulin/IGF1 pathway, acetylation and O-glycosylation of components of NF-kB pathway, and DNA damage. NF-kB system induces entropic ageing process and release of SASP.