Age-associated changes in the heart: implications for COVID-19 therapies

Abstract

Cardiac aging involves progressive structural, functional, cellular, and molecular changes that impair heart function. This review explores key mechanisms, including oxidative stress, mitochondrial dysfunction, impaired autophagy, and chronic low-grade inflammation. Excess reactive oxygen species (ROS) damage heart muscle cells, contributing to fibrosis and cellular aging. Mitochondrial dysfunction reduces energy production and increases oxidative stress, accelerating cardiac decline. Impaired autophagy limits the removal of damaged proteins and organelles, while inflammation activates signaling molecules that drive tissue remodeling. Gender differences reveal estrogen's protective role in premenopausal women, with men showing greater susceptibility to heart muscle dysfunction and injury. After menopause, women lose this hormonal protection, increasing their risk of cardiovascular conditions. Ethnic disparities, particularly among underserved minority populations, emphasize how social factors such as access to care, environment, and chronic stress contribute to worsening cardiovascular outcomes. The coronavirus disease pandemic has introduced further challenges by increasing the incidence of heart damage through inflammation, blood clots, and long-term heart failure, especially in older adults with existing metabolic conditions like diabetes and high blood pressure. The virus's interaction with receptors on heart and blood vessel cells, along with a weakened immune response in older adults, intensifies cardiac aging. Emerging therapies include delivery of therapeutic extracellular vesicles, immune cell modulation, and treatments targeting mitochondria. In addition, lifestyle strategies such as regular physical activity, nutritional improvements, and stress reduction remain vital to maintaining cardiac health. Understanding how these biological and social factors intersect is critical to developing targeted strategies that promote healthy aging of the heart.

Keywords: COVID-19 cardiovascular complications; cardiac aging; health disparities; mitochondrial dysfunction; oxidative stress.

Figure 1

Cardiovascular anatomy. This figure shows a visual representation of some of the relevant cardiovascular anatomy. Labeled structures include the heart chambers, valves, capillary system, and a cardiac muscle cell.

Figure 2

Effects of aging on heart. As the heart ages, it experiences a range of structural, functional, cellular, and genetic changes. Structural alterations include vascular stiffness, thickening of the left ventricular wall, fibrosis, and enlargement of the atrium. Functional changes manifest as reduced cardiac output, atherosclerosis, and dysfunction in cardiac autonomic regulation. At the cellular level, there’s mitochondrial dysfunction, heightened fibrosis, amyloid fibril formation, and endothelial senescence. Additionally, genetic alterations such as DNA damage, endothelial dysfunction, and telomerase shortening occur with age.

Figure 3

A summary of different factors that contribute to the differences in cardiac agedness in men and women. The incidence of cardiovascular complications in COVID-19 pathology appears to be linked to differences in sex and gender. This likely contributes to the greater severity and poorer outcomes of SARS-CoV-2-mediated disease in male patients compared to females.

Figure 4

Cardiovascular complications of COVID-19 in elderly people. COVID-19 exacerbates cardiac injuries, especially in older patients with a cardiovascular medical background, increasing the likelihood of developing critical conditions.

Figure 5

To prevent the impact of COVID-19 on aging hearts, implement measures such as vaccination, adherence to public health guidelines, managing chronic conditions, staying active, and seeking regular medical care.

Figure 6

Ways COVID-19 contributes to cardiac aging. A COVID-19 infection can cause macroscopic and microscopic altercations that induce cardiovascular dysfunction. Image created by Biorender.com.