246
endurance training is considered to be safe in aging and regarded as a countermea-
sure for aging [ 186 ].
Typically, endurance exercise can increase the physiological demands of theheart and of note, a meta-analysis from 23 studies comprising a total of 294 cases
reported that following endurance exercise, there was a 2% reduction in left ven-
tricular ejection fraction (LVEF) transiently [ 187 ]. Strikingly, a small change of 1%
reduction in LVEF has been shown to increase the risk of fatal and nonfatal cardio-
vascular events in asymptomatic dialysis patients [ 188 ]. Diminution of right ven-
tricle function is also observed with endurance exercise [ 189 ]. In another study, rats
subjected to long term treadmill running protocol for 18 weeks (2 weeks of progres-
sive training +16 weeks of steady state 1-hour running), a time approximately trans-
lates to 10 years of endurance exercise training in humans, exhibited eccentric
myocardial hypertrophy, diastolic dysfunction, atrial dilation, together with colla-
gen deposition and higher fibrotic marker expression in both atria and right ventricle
[ 153 , 190 – 193 ]. These morphological and functional changes are essentially a close
mimic of the “athlete’s heart” as described in humans. Thus, given the increasing
trend of endurance exercise at an alarming rate over the past decades [ 194 , 195 ],
there is an immediate need for detailed understanding of endurance training in the
context of the myocardium. Further, since it was reported that an acute reduction in
LVEF and myocardial dysfunction could follow a prolonged strenuous exercise due
to increased oxidative signaling [ 196 , 197 ], the relevance of endurance exercise to
Nrf2-antioxidant signaling which is intrinsically disrupted in the aged myocardium
can be highly important from the standpoint of cardiovascular fitness. More detailed
studies with different aged animals spawning 6–24 months subjected to endurance
training (mild, moderate, intense) over prolonged period of time in the presence and
absence of Nrf2 will comprehensively determine the impact of endurance exercise
stress on normal and forced (redox stressed) cardiac aging.
9 Conclusions and Perspectives
Overall, the central theme presented here suggests that Nrf2 is crucial to avail bene-
fits of exercise. Discrete modes of exercise result in a differing degree of favorable
effects on cardiac health. Considerable evidence indicates that the cellular redox sta-
tus and signaling per se can shift a physiological adaptation to the pathological event
and vice-versa in response to any exercise training. Specifically, endurance exercise
stress may provoke cardiac exertion and instability in the aged animals. Since Nrf2
and its function progressively declines over age, within a specific segment (age
group), for instance, older segment, distinct individuals will likely possess varying
levels of redox control. In addition, no two individuals will present themselves with
stress levels to a similar extent. Relevant to the real time setting, in certain healthy
individuals with lower Nrf2 levels and antioxidant threshold who do not manifest
any apparent symptoms, an abstinence of competitive exercise may be required.
Further, exercise and Nrf2-dependent redox alterations either individually or in
M. Narasimhan and N.-S. Rajasekaran