Decreased Proteasome-Mediated Degradation in T Cells from the Elderly: A Role in Immune Senescence

• Published in: Cellular immunology 1999-03, Vol.192 (2), p.167-174
• Main Authors: Ponnappan, Usha, Zhong, Mingzheng, Trebilcock, Gina Uken
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Aging - immunology; Cysteine Endopeptidases - physiology; DNA-Binding Proteins - metabolism; Humans; I-kappa B Proteins; immune senescence; IκB; Multienzyme Complexes - physiology; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha; proteasome; Proteasome Endopeptidase Complex; Receptors, Interleukin-2 - analysis; T lymphocytes; T-Lymphocytes - metabolism; Tumor Necrosis Factor-alpha - pharmacology; ubiquitin
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1006/cimm.1998.1418

Induction of NFκB is a highly regulated process requiring phosphorylation, ubiquitination, and proteasome-mediated degradation of the cytosolic inhibitor IκBα. Analyses of the regulation of IκBα in TNF-α-treated T lymphocytes from young and elderly donors revealed severely compromised degradation of IκBα in T cells from the elderly. Examination of activation-induced phosphorylation and ubiquitination of IκBα did not demonstrate any significant age-related alterations. However, examination of proteasome activity in these T cells using fluorogenic peptide assays revealed a significant age-related decline in chymotryptic activity. These results suggest that a decline in proteasome activity results in a failure to fully degrade IκBα in the elderly. This failure to degrade IκBα may underlie both the observed decrease in NFκB induction and the IL-2 receptor expression in TNF-treated T cells during aging. Thus, decreased proteasome-mediated degradation may be central to immune dysfunction that accompanies aging.