Biomedical Engineering Reference
In-Depth Information
RS have been found accumulated in aged animals, such as
•
O
2
-
, hydrroxyl radical,
and H
2
O
2
, reactive nitric oxide, and peroxynitrite. Higher lipid peroxidation and
products were also determined in the old animals, including 4-hydroxyhexenal,
malondialdehyde and LPC. In addition, protein oxidation was also detected; for
instance, level of AGEs was reported increased with age, including argpyrimidine,
l uorolink, pyrraline, and imidazolone derivatives of arginine. In contrast, the
anti-oxidative defense systems are weakened by age, such as the reduced anti-
oxidative capacity of serum. h erefore, the age-related redox imbalance occurring
under oxidatively stressed conditions is likely caused by the net ef ect of weakened
anti-oxidative defense systems and the incessantly increasing production of RS. As
discussed above, most of these redox mediators, like RS, LPC and AGE, have been
Inflammatory mediators
(Histamine, Thrombin, Phorbol
ester, Endothelin, Factor Xa,
Tissue factor)
Proinflammatory
cytokines
(TNF-
α
; IL-1,2,4,6; IFN-
γ
;
VEGF, GM -CSF
)
Cell
activation
Oxidants
(AGEs,
Bioactive lipids
(oxLDL, LPA, LPC, PAF)
-
HOO
222
)
Inflammatory Adhesion Molecules
(e.g. E-selectin, P-selectin, VCAM-1, ICAM-1)
Inflammatory Response
Leukocyte Infiltration
Fig. 1
Age-related stimuli that cause upregulation of inl ammatory AMs. Diverse aging-
related stimulators can upregulate expression of AMs on EC. Uncontrolled expression of AMs
causes dysregulated leukocyte-EC interactions, leading to improper recruitment of leukocytes.
(Unpublished.)
Pro-inflammatory Status of Aging
One inescapable cellular consequence of oxidative stress is the formation of a
primary driving force for increased activation of redox-regulated transcription
factors, such as NF-κB, which regulates the expression pro-inl ammatory molecules
(Fig. 2)
(Chung
et al.
2006). Most of the data indicated that the molecular events
involved in age-related NF-κB activation requires phosphorylation by inhibitor of
kappaB (IκB) kinase (IKK) / NF-κB-inducing kinase (NIK) and mitogen-activated
