Lowering of NF-κB p65 protein in the liver appears to be a common biological effect across a wide range of anti-ageing strategies, including dietary, pharmaceutical, and genetic interventions, highlighting this inflammatory regulator as a potential unifying target for promoting longevity and metabolic resilience.
December 2024 – GeroScience
Key takeaways
- Common target across longevity approaches: Reduced levels of the inflammatory protein NF-κB p65 were consistently observed in the liver across seven out of ten tested anti-ageing strategies, including caloric restriction, rapamycin, and genetic models of slow ageing. This suggests a shared biological pathway that may underpin many life-extending interventions
- Inflammatory signalling is selectively suppressed: While p65 was consistently downregulated, other NF-κB components like p50 and upstream regulators such as IKKα and IKKβ did not show uniform changes. This indicates that specific suppression of p65, rather than broad pathway inhibition, might be sufficient to dampen age-related inflammation in the liver
- Downstream inflammatory and metabolic genes follow suit: Key genes regulated by p65, including HNF4α, IL-1β, and CRP, were also reduced in multiple models. These genes are tied to inflammation and liver metabolism, implying that p65 downregulation could help modulate both immune function and metabolic health with age
- Potential for novel therapeutic targeting: Because p65 downregulation emerged across diverse and mechanistically different interventions, it offers a promising molecular target for future anti-ageing therapies. Modulating p65 levels could support systemic resilience against age-related inflammatory decline and may complement other lifestyle or pharmacological approaches to longevity
Read the article at: Elmansi, Ahmed M., et al. “Downregulation of the NF-κB protein p65 is a shared phenotype among most anti-aging interventions.” GeroScience (2024). https://doi.org/10.1007/s11357-024-01466-9
