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Notably, cardiac aging in the murine model is highly consistent with the age-related cardiac changes observed in a healthy human population [ 70 ]. Indeed, histo-
pathological, echocardiographic and signaling studies indicate that the murine heart
undergoes subendocardial, interstitial fibrotic changes, amyloid deposition along
with hypertrophy, diastolic dysfunction, reduced functional reserve and molecular
alterations with age parallels that of elderly humans [ 70 – 75 ]. Like other tissues, a
human heart also has the replicative potential [ 76 , 77 ] and thus myocardial aging
can also be accompanied by an imbalance between the reduction of myocyte growth
and death. Along these lines, an interesting study demonstrated that the endomyo-
cardial biopsies from patients with heart failure revealed shortened telomeres,
increased cellular senescence and cell death [ 78 ]. In addition, telomeric length in
circulating leukocytes has been shown to be a representative of that in the cardiac
myocytes and role of oxidant stress in telomere attrition in this context is well
known [ 79 – 81 ]. Using telomerase ablation, researchers were also able to generate
a premature aging animal model that was characterized by an enhanced apoptotic
myocyte death along with poor myocyte growth [ 82 ]. Interestingly, lack of telomer-
ase and the subsequent telomere erosion also led to increased oxidative stress in
cardiomyocytes [ 83 ] thus hinting at the fact that the redox-telomere axis can operate
in a loop perpetuating each other in the myocardium. Further, the redox perturba-
tions associated with an aged heart can particularly induce a functional loss of either
cardiomyocyte and/or the supporting cells eventually accruing and/or eliminating
those from the system [ 84 – 86 ]. Very recently, under steady state conditions, physi-
ological aging is shown to be accompanied by shifts in the composition of heart-
associated leukocyte populations has been reported [ 87 ]. Further, the same study
demonstrated that heart-directed immune responses along with myocardial func-
tional and structural alterations may spontaneously occur in the elderly, without the
presence of any apparent tissue damage or infection. These shifts in the cardiac-
resident cells can influence the local milieu modulating several events and affecting
the heart regenerative capacity with age progression [ 78 , 88 , 89 ]. At this juncture, it
is noteworthy that the age-accompanied oxidative changes and certain clinical man-
ifestations observed in humans are also recapitulated in the myocardium of murine
models [ 70 , 90 – 93 ]. Thus, the more we appreciate and comprehend the redox con-
trol and environment, the better we will understand the biology of the heart and thus
on the crosstalk of aging and cardiovascular health.
5 Response to Redox Stress – Nrf2 Signaling and Relevance
to Cardiac Aging
In general, the cellular system is inherently endowed with several antioxidants
based counteracting mechanisms to respond to and balance the increase in oxidative
burden. They either individually or in combination eliminate the free radicals, scav-
enge and neutralize ROS and their precursor, inhibit ROS generation or sequester
the redox-active metal ions required to catalyze the Fenton-type ROS generating
13 Cardiac Agingfi– Bene ts offiExercise, Nrf2 Activation andfiAntioxidant Signaling