Mike KS Chan 1, Michelle BF Wong 3, Dmytro Klokol 1,2* , Olha Nishkumai 1,2, Jonathan RT Lakey 4,5 and Natali Shyshkina 1,2,5
1 European Wellness Biomedical Group (Edenkoben, Germany)
2 European Wellness Academy (Malaysia, APEC)
3 Stellar Biomolecular Research (Edenkoben, Germany)
3 University of California, Irvine, Department of Surgery (Irvine CA, USA)
4 University of California, Irvine, Department of Biomedical Engineering (Irvine, CA, USA)
5 Bogomolets National Medical University, Department of Internal Medicine#2 (Kyiv, Ukraine)
***Corresponding author:** Dmytro Klokol, European Wellness Academy (Ukraine, Malaysia, APEC)
**Citation:** Chan MKS, Wong MBF, Klokol D, Nishkumai O, Lakey JRT, Shyshkina N. Peptides in Cardiology: Preventing Cardiac Aging and Reversing Heart Disease. Adv Clin Med Res. 5(4):1-16.
**Received**: November 26, 2024 Published: December 06, 2024
**Copyright**©2024 genesis pub by Klokol D et al. CC BY-NC-ND 4.0 DEED. This is an open-access article distributedunder the terms of the Creative Commons Attribution-NonCommercial-No Derivatives 4.0 International License.,This allows others distribute, remix, tweak, and build upon the work, even commercially, as long as they credit the authors for the original creation.
**DOI:**https://www.frankenthalerfoundation.org
Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide. As the population ages, the incidence of heart disease related to aging has surged, highlighting the need for innovative therapeutic strategies. Among these, peptides have emerged as a promising class of molecules due to their unique ability to modulate multiple physiological pathways involved in cardiac aging, repair, and regeneration. This review explores the role of various peptides in preventing cardiac aging, promoting myocardial repair, and reversing heart diseases, focusing on their mechanisms of action, clinical potential, and potential future prospects.
Cardiac aging; Cardiomyopathy; Peptides; Cardiovascular disease; Stem cells; Regenerative medicine; Cardiac regeneration
Cardiac aging is a complex physiological process that contributes to the development of various cardiovascular diseases (CVDs), which remain the leading cause of mortality worldwide. As populations age, the burden of heart diseases escalates, impacting both longevity and quality of life. The pathophysiology of cardiac aging involves structural and functional alterations in the heart and vasculature, including myocardial stiffness, reduced cardiac output, and endothelial dysfunction. These changes predispose individuals to conditions such as hypertension, heart failure, atrial fibrillation, and coronary artery disease. The impact of heart diseases on longevity is profound, shortening life expectancy, while the associated decline in cardiac function often leads to diminished quality of life. Understanding the mechanisms of cardiac aging is critical for developing strategies to prevent or mitigate the effects of cardiovascular diseases, emphasizing the need for early detection, lifestyle interventions, and pharmacological therapies. In this article, we explore the biological mechanisms of cardiac aging, its contribution to heart diseases, the impact on overall health, and the importance of prioritizing cardiovascular health in healthcare systems [1].
The human heart undergoes various age-related changes that affect both its structure and function. These changes are influenced by genetic factors, environmental exposures, lifestyle habits, and co-morbidities. As the global population continues to age, CVDs are becoming an increasingly important issue, contributing significantly to morbidity, mortality, and healthcare costs. The World Health Organization estimates that by 2030, CVDs will account for more than 23 million deaths annually, representing nearly half of all global deaths. Cardiovascular health, therefore, plays a central role in determining both longevity and quality of life in older adults [2].
Cardiac aging is a complex process involving both structural and functional changes that contribute to the increased prevalence of heart disease in older adults. Age-related cardiomyopathies, including dilated, hypertrophic, restrictive, and amyloid cardiomyopathies, pose significant challenges to clinical management. Understanding the molecular and cellular mechanisms behind these changes is crucial for developing more effective therapeutic strategies. Future research into targeted therapies, including gene editing, regenerative medicine, and novel pharmacological agents, will be essential in addressing the growing burden of cardiovascular disease in the aging population [1-3].
Cardiac aging has a profound impact on both longevity and the quality of life. The gradual decline in heart function and the increasing prevalence of heart disease reduces life expectancy in aging populations. More importantly, cardiovascular diseases significantly impair the quality of life, as individuals with CVD often experience fatigue, shortness of breath, limitations in physical activity, and an increased risk of disability.
Heart failure, particularly, is associated with a high symptom burden and poor functional status, leading to frequent hospitalizations, reduced independence, and increased caregiver burden. The psychological and emotional impacts of living with a chronic cardiovascular condition, such as depression and anxiety, further exacerbate the decline in quality of life [4]
The growing prevalence of cardiovascular diseases in aging populations presents a significant challenge to healthcare systems worldwide. The costs associated with the management of heart diseases—including hospitalizations, long-term care, medications, and surgeries—place a substantial strain on healthcare resources. Moreover, the management of older patients with multiple co-morbidities requires a comprehensive, multidisciplinary approach.
The heart, like other organs in the body, undergoes a series of changes as a person ages. While some of these alterations are considered part of the normal aging process, others may contribute to the development of cardiovascular diseases, including heart failure, arrhythmias, and cardiomyopathies. The intersection of aging and cardiovascular disease is a growing area of research, as the aging population continues to expand globally. Understanding the mechanisms behind age-related cardiac changes, along with the pathogenesis of cardiomyopathies, has important implications for the prevention, diagnosis, and treatment of heart disease in older adults.
Cardiac aging is characterized by both cellular and molecular alterations that reduce the heart's efficiency and its ability to respond to stress. Let’s look into some key mechanisms involved in cardiac aging. As the heart ages, it undergoes both structural and functional changes that are thought to contribute to its diminished capacity to adapt to stressors, whether physiological or pathological. One of the most common structural changes observed in the aging heart is left ventricular hypertrophy, often due to long-standing hypertension or increased afterload. LVH is associated with both systolic and diastolic dysfunction, increased myocardial stiffness, and impaired relaxation [5-7].
Myocardial Fibrosis is another hallmark of cardiac aging. As part of the remodeling process, excessive collagen deposition occurs within the myocardium, particularly in the interstitial and perivascular spaces. This fibrosis contributes to ventricular stiffness, reduces compliance, and impairs relaxation during diastole. It is a major contributor to diastolic heart failure in the elderly [8].
Aging also affects the coronary microvasculature, leading to endothelial dysfunction, impaired vasodilation, and reduced capillary density. This contributes to ischemia in older hearts, even in the absence of significant coronary artery disease. With age, there is a decline in the number and function of pacemaker cells in the sinoatrial node, as well as fibrosis in the conduction system. This can result in arrhythmias, including atrial fibrillation, which is more common in the elderly.
One of the earliest and most common functional changes in the aging heart is diastolic dysfunction. This refers to impaired relaxation and filling of the ventricles during diastole. The increased stiffness of the left ventricle, due to fibrosis and other factors, makes it harder for the heart to fill with blood, which can ultimately lead to heart failure with preserved ejection fraction (HFpEF).
Although less common than diastolic dysfunction, systolic dysfunction can also occur with aging. This is often due to progressive myocardial damage, loss of myocytes, and changes in the contractile proteins within the heart muscle, leading to a reduced ejection fraction and the development of heart failure with reduced ejection fraction (HFrEF) [9].
The autonomic nervous system undergoes changes with age, leading to increased sympathetic activity and reduced parasympathetic tone. This results in altered heart rate variability and contributes to the increased risk of arrhythmias in elderly patients [13,15].
Cardiomyopathies are a heterogeneous group of diseases characterized by structural and functional abnormalities of the heart muscle. In older adults, cardiomyopathies may arise due to age-related changes, underlying co-morbidities, or genetic predisposition [10,12].
While Age-Related Dilated Cardiomyopathy (DCM) is typically associated with younger populations, age-related DCM is an increasingly recognized condition in elderly patients. The pathogenesis of DCM in older adults is multifactorial and involves both intrinsic aging mechanisms and the accumulation of risk factors such as hypertension, diabetes, and coronary artery disease. Myocyte apoptosis, loss of contractile proteins, mitochondrial dysfunction, and impaired calcium handling contribute to the progressive dilation of the ventricles and the reduced ability to contract effectively [10].
Hypertrophic Cardiomyopathy (HCM) is a genetically inherited condition characterized by asymmetric hypertrophy of the left ventricle. While it is primarily diagnosed in younger individuals, age-related worsening of HCM can occur, with increased fibrosis, myocyte disarray, and progressive systolic dysfunction. The underlying genetic mutations (e.g., mutations in the sarcomeric protein genes) continue to drive disease progression over time, but the clinical manifestations often become more apparent with advancing age, as the heart’s compensatory mechanisms become less effective.
Restrictive Cardiomyopathy (RCM), characterized by impaired ventricular filling due to increased myocardial stiffness, is often seen in elderly individuals. In particular, age-related fibrosis and amyloid deposition can lead to RCM. Systemic amyloidosis, often seen in the elderly, can infiltrate the myocardium, leading to restrictive filling and diastolic heart failure. Age-related RCM can also be exacerbated by conditions like hypertension or diabetes.
Amyloid Cardiomyopathy, mostly in elderly populations, the accumulation of amyloid proteins—particularly transthyretin amyloidosis (ATTR)—is a significant cause of restrictive cardiomyopathy. ATTR amyloidosis, which can present with heart failure, arrhythmias, and conduction abnormalities, is becoming more recognized in older adults. The accumulation of misfolded amyloid fibrils in the myocardial interstitium results in a stiff heart with impaired relaxation [14].
The pathogenesis of age-related cardiomyopathies involves a combination of genetic predispositions, cellular senescence, mitochondrial dysfunction, oxidative stress, and inflammatory processes.
Key mechanisms include:
Given the increasing burden of age-related cardiomyopathies, research is focused on finding effective interventions to prevent or reverse these processes. To address the growing burden of cardiovascular diseases, healthcare systems must prioritize early detection, prevention, and the development of personalized treatment strategies [17]. This includes:
