CONSTITUTIVE ACTIVATION OF NF-KAPPA-B IN AN ANIMAL-MODEL OF AGING

The pathophysiology of many disease states observed in aged individual s has been linked to the dysregulated production of several pleiotropi c cytokines. We have demonstrated that NF-kappa B, a major transcripti onal regulator of these aberrantly expressed cytokines, exists in a co nstitutively activated state in cells obtained from the major lymphoid organs of aged animals, Therapeutic treatment with dietary antioxidan ts or with agents capable of activating the peroxisome proliferator-ac tivated receptor (PPAR)-alpha was able to correct the abnormal nuclear NF-kappa B activity, reduce lipid peroxide levels, and eliminate the dysregulated expression of cytokines and other genes under NF-kappa B control. These results suggest that abnormal activation of NF-kappa B in aging contributes to the dysregulated expression of certain pleiotr opic cytokines. Effective therapeutic regimens for aging and other inf lammatory disease states might benefit from the administration of anti oxidants or other agents which specifically activate PPAR-alpha.