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defense mechanisms leads to reduced cardiac performance, dysfunction, fibrotic
remodeling, and inflammation through sustained oxidative stress [ 75 , 133 , 147 ].
Accordingly, our previous study demonstrated that acute exercise training stimu-
lated nuclear translocation of Nrf2 and transcriptional activation of its target anti-
oxidants in the heart of WT, while the Nrf2 ablated mice suffered from severe OS
upon acute exercise [ 96 ]. Overall findings reveal that exercise may exert a beneficial
effect in protecting the myocardium through Nrf2-dependent EpRE/ARE signaling
pathway, but benefits to exercise differ with age. Aged individuals display several
cardiac structural and functional impairments and are increasingly vulnerable to
develop pathological remodeling relative to younger ones.
Age-related diminution in myocardial performance and tolerance to exercise areknown [ 2 ] with the peak maximal oxygen capacity (VO 2 ) impairs either in the nor-
mal or highly active healthy but older people influencing the cardio-respiratory
health [ 148 – 153 ]. Recent reports indicate that the physiological level of Nrf2 and its
transactivation ability is reduced in aging [ 75 , 154 ]. An earlier report from our labo-
ratory has shown that the aging mice develop maladaptive oxidative stress and dia-
stolic dysfunction due to exhaustion of existing antioxidant pool to overcome the
endurance stress (Fig. 13.4) [ 155 , 156 ]. Studies in healthy older men indicated a
reduced response to acute exercise due to decreased β-adrenergic responses [ 157 ].
Recent reports on β1-adrenergic mediated Nrf2/HO-1/HMGB1 axis demonstrated
hypoxia/reoxygenation (H/R)- injury in neonatal rat cardiomyocytes [ 158 ]. Future
investigation on the cross-talk between Nrf2 and β-adrenergic signaling pathways in
acute exercise training during aging would be fascinating.
Fig. 13.4 Chronic endurance exercise induces diastolic dysfunction. Mitral valve inflow measure-
ments using pulse wave Doppler (Visual Sonics, Vevo2100 Echocardiography Imager) illustrates
the prolonged endurance exercise cause diastolic dysfunction in WT or Nrf2−/− mice on aging
13 Cardiac Agingfi– Bene ts offiExercise, Nrf2 Activation andfiAntioxidant Signaling