Biomedical Engineering Reference
In-Depth Information
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Signaling Kinases: MAPK, NIK/IKK
Transcription Factor: NF-
B
Pro-inflammatory Molecules:
Cytokines, AMs, iNOS, COX-2
Chronic Inflammation
Aging,
Age-related Diseases
Fig. 2
Major molecular pro-inl ammatory pathways involved in aging. (Unpublished.)
protein kinases (MAPK). For instance, 4-hydoxyhexenal triggered NF-κB activation
by IκB phosphorylation via the IKK/NIK pathway, through increased p38 kinase
and extracelluar signal-regulated kinase, but not c-jun kinase signaling.
Redox-sensitive activation of NF-κB-dependent genes is a major culprit
responsible for the systemic inl ammatory process during aging. In aged organisms,
NF-κB-regulated inl ammatory reactions lead to a chronic pro-inl ammatory
state as evidenced from the activation of pro-inl ammatory gene expression. h e
activation of NF-κB is responsible for transcription of not only pro-inl ammatory
proteins such as TNF-α, interleukins such as IL-1, IL-2, and IL-6 as well as the
chemokines iNOS and COX-2, but also AMs (Chung
et al.
2006). h e dif erence in
the NF-κB activation observed during aging could be explained by a much faster
and more extensive IκB degradation in old than young, leading to more abundant
expression of ICAM-1 in the old vascular smooth muscle cells, for example. A
greater activation of the NIK/IKK/IκB pathway in aorta from old rats was found;
therefore, this pathway may be responsible for increased levels of aortic P-selectin
and VCAM-1 in the old rats.
As proposed in the molecular inl ammation hypothesis of aging, a state of
chronic, low-grade inl ammation mediated by redox-sensitive transcription
