Cardiac System during the Aging Process

Abstract

The aging process is accompanied by a continuous decline of the cardiac system, disrupting the homeostatic regulation of cells, organs, and systems. Aging increases the prevalence of cardiovascular diseases, thus heart failure and mortality. Understanding the cardiac aging process is of pivotal importance once it allows us to design strategies to prevent age-related cardiac events and increasing the quality of live in the elderly. In this review we provide an overview of the cardiac aging process focus on the following topics: cardiac structural and functional modifications; cellular mechanisms of cardiac dysfunction in the aging; genetics and epigenetics in the development of cardiac diseases; and aging heart and response to the exercise.

Figure 1.

Age-dependent cardiac structural modifications. The aged heart shows several structural changes when compared with younger adults. These cardiac modifications include epicardial fat deposition, aortic valve calcification, atrial hypertrophy, dilatation, and concentric left ventricle hypertrophy. At the cellular level, cardiomyocytes apoptosis is observed, and the remaining cardiomyocytes are under hypertrophy. The fibroblasts cells and fibrosis augments with aging. These age-dependent structural modifications may be affected by factors including gender (modified from ref. [8]).

Figure 2.

Epicardial torsion and endocardial circumferential shortening and relationship to subepicardial and subendocardial fiber orientations. Epicardium is represented in red and endocardium in green. Younger adults: (A) the heart presents oblique subepicardial fibers that lead to a rotation of the apex regarding the base (B) and a clockwise direction. This rotation is quantified in terms of circumferential-longitudinal angle (C). Epicardial torsion has a larger radius, giving it a mechanical advantage over the subendocardium, driving subendocardial bundles to narrow in a direction nearly 90º away from the subendocardial bundle’s orientation (circumferential plane) (D). The torsion to shortening ratio (TSR) quantifies the subepicardial to subendocardial interaction. Augmented values of TSR indicate reduced subepicardial effect over the subendocardium. Aging: there is an increase in the rotational angle E and torsional angle F. Endocardial circumferential shortening does not change compared with young adults, thus TSR increases, suggesting a reduced interaction between subepicardium and subendocardium. Aging - hypertension: there are no changes in the rotational and torsional angles when compared with young adults (G), even though the endocardial circumferential shortening is increased (thick dark green arrows, shortening H), indicating augmented interaction between the subepicardium and subendocardium and hence, the TSR is reduced (modified from ref. [10]).

Figure 3.

Normal age-associated changes in ECG measurements. A) Young adult vs old adult. The P wave represents auricular depolarization. P wave duration can exhibit a minor increase in old adult individuals. The PR interval, representing atrioventricular conduction, increases from 159 ms (individuals averaging 25-35 yrs) to 172 ms (old individual). The QT represents the time taken for ventricular depolarization and repolarization. The QT interval slightly increases with aging heart. Other findings that may became more prevalent with aging such as increased QRS voltage, Q waves, QT interval prolongation, and ST-T-wave anomalies, are usually linked to an increase of cardiovascular risk. B) Cardiac axis, young adult, vs old adult. With aging, individual exhibits a leftward shift of the QRS axis (Based on [16]).

Figure 4.

Graphic summary of the aging heart. Major cardiac structural modifications: left atrium dilatation caused by the increase of diastolic pressure because of slower ventricular filling; cardiac hypertrophy, characterized by a significant increase of the LV wall with a reduction of the LV chamber size; Aortic valve calcification and epicardial fat accumulation. Major functional modifications: diastolic function declines due to impairments of Ca²⁺ cycling/handling, affected by oxidative damage of SERCA, and ventricular-atrial stiffening in the senescence myocardium; systolic function is usually preserved at least at rest. Cardiac autonomic dysfunction due to impaired central integrations, impaired baroreceptor output and decreased sinoatrial response. Major cellular modifications: total number of cardiomyocytes declines, and the remaining undergo hypertrophic; fibroblast cells proliferation; increase fibrosis and amyloid fibrils formation; mitochondrial dysfunction that leads to ROS accumulation. ROS drives cellular oxidative stress and mtDNA damage which is reflected in an impairment of the energetic and metabolic state that disrupts homeostasis. Major genetic modifications include chemical DNA damage, mutations in the DNA and epigenetic modifications that change genes activity; telomere length shortening that leads to cell senescence and apoptosis. Cardiac adaptation to exercise: maximal HR decreases leading to chronotropic incompetence and thus to maladaptive symptoms in response to exercise. To compensate for the reduction of maximal HR, SV increases, however it seems to be slightly affected in the aged heart. Moreover, the MAC decreases which contributes to modifications in the mechanism that regulates oxygen dynamics in response to exercise.