Biomedical Engineering Reference
In-Depth Information
POSSIBLE INTERVENTIONS IN AGE-RELATED AM
CHANGES
Considering the ef ects of dysregulated AMs during aging on various age-
associated diseases, to seek possible interventions in age-related AM changes by
various means is important, and should be of great interest to researchers. In this
section, we present a few known experimental paradigms by which the activation
of AMs was ef ectively modulated.
Calorie restriction (CR) is the most powerful nutritional intervention of the
aging process, and researchers have now accepted CR as the only established anti-
aging experimental paradigm. Although the molecular mechanism of ef ects of CR
is still not clearly known, its anti-aging ef ects are thought to be due mainly to its
powerful resistance against oxidative stress and ability to maintain a proper cellular
redox status. It has been clearly demonstrated that CR suppresses age-related
diseases, modulates redox-sensitive transcription factors and inl ammation, and
restores various membrane-associated functions in experimental animals (Chung
et al.
2006, Yu and Chung 2006).
Accumulating evidence indicates that anti-oxidative CR signii cantly
attenuates NF-κB, TNF-α, interleukins (IL-1β, IL-2, and IL-6), chemokines (IL-8
and RANTES) and AMs (Chung
et al.
2009). h e increased levels of aortic AMs,
VCAM-1 and P-selectin, as well as sAMs, E-selectin, P-selectin, VCAM-1 and
ICAM-1 during aging in non-restricted old rats were ef ectively blunted by CR, and
leukocyte ini ltration in the old rats was also reduced by CR (Son
et al.
2005). CR
even initiated in late adulthood confers benei cial ef ects, such as the attenuation
of oxidative stress, enhanced expression of HSP-70, neural plasticity markers
NCAM, and PSA-NCAM, and reduced levels of GFAP (Kaur
et al.
2008).
Antioxidants and anti-inl ammatory treatments are also ef ective in controlling
the level of AMs in the elderly. Polyphenols or vitamin E may assist in preventing
cardiovascular disease, in part by decreasing EC expression of pro-inl ammatory
cytokines, AMs, and monocyte adhesions. Ferulate is a well-described natural
antioxidant found in plants, and ferulate has exhibited its anti-oxidative action
by reducing the NF-κB-induced, pro-inl ammatory VCAM-1 and ICAM-1
in kidney from old Sprague-Dawley rats (Jung
et al.
2009). Betaine suppresses
pro-inl ammatory signaling during aging including the VCAM-1 and ICAM-1
expression through its anti-oxidative ef ects as betaine is involved in glutathione
metabolism.
Aberrant AMs with age could also be regulated by anti-inl ammatory treatments.
Increased ICAM-1 was decreased by etanercept treatment, which binds and
inactivates TNF-a. Anti-TNF-a treatment exerts anti-aging, vasculoprotective
ef ects (Csiszar
et al.
2007). Aspirin is one of the most commonly used non-steroidal
anti-inl ammatory drugs. In a recent study, we investigated the ef ect of short-term,
low dose aspirin intake on the modulation of pro-inl ammatory NF-κB activation
