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7 Moderate Exercise Training (MET) and Stabilization
of Nrf2-Antioxidant Signaling in the Myocardium
Given the role of Nrf2 during short sub-maximal (acute) and maximal endurance
stress in aging animals, a moderate exercise training (MET) for a longer duration
(6 weeks) seems to significantly augment nuclear Nrf2 level in both the young and
aging heart. Subsequent to MET-induced Nrf2 stabilization, an increase in the tran-
script and protein levels of major Nrf2-targets (i.e. glutathione reductase, hemoxy-
genase- 1, glucose 6-phosphate dehydrogenase and glutamyl cysteine ligase) was
also demonstrated [ 75 ]. Prior studies have established that a short- and long-term
MET promoted myocardial perfusion and functional capacity in animals and
humans with ischemic heart disease, and heart failure [ 152 , 156 , 159 – 166 ]. Notably,
MET has been beneficial in preventing age-related cardiovascular diseases [ 15 ,
167 ]. We along with others have shown that, although there was an MET-induced
protection seen in aged animals the magnitude of benefits was not as strong as that
noted in the younger group [ 75 , 168 ]. However, the precise mechanisms are still
elusive. Based on our previous study, it can be agreed upon that moderate exercise
training in aging animals can escalate Nrf2 signaling and restore redox homeostasis
[ 75 ], but the inherently high oxidative burden that exists during aging could require
a much stronger Nrf2 activation and its associated antioxidant signaling than that is
currently offered by MET. In other words, optimal benefits of MET could depend
on the optimization of redox and this could be one of the crucial points where the
young and old diverge with respect to MET’s effect. Further, an interesting finding
has demonstrated that when animals were subjected to swimming in warm water at
30–32 °C with a duration of 60 min (5 days/week) for 10 weeks that represents
MET, showed neovascularization along with improved structure and function of the
cardiovascular system [ 169 – 171 ]. Although MET can enhance Nrf2 signaling in the
aging model, how far MET can be effective in improving the proangiogenic process
in aging is unclear currently. Since, it has been reported that Nrf2 can activate
HIF-1α/VEGF pathway [ 172 , 173 ], investigating the molecular cross-talk between
Nrf2 with angiogenesis in response to MET in young and aged hearts could also be
worthwhile to narrow the gap in our understanding along these lines. Nevertheless,
moderate exercise training is still the most preferred and applied training modality
for improving cardiac fitness. However, new training modes and/or strategies are in
need for the aged segment. With the current understanding, we suppose an in-depth
animal study involving a combination of MET along with a titrated nutraceutical or
dietary mode of Nrf2 activation through Protandim or Broccoli, that contains sul-
foraphane (an activator of Nrf2) respectively will be an ideal starting point. And,
hopefully, more studies in this line of thought can provide impetus to explore an
effective strategy to improve the cardiac fitness in the elderly.
M. Narasimhan and N.-S. Rajasekaran