Aging is a key contributor to the pathogenesis of cardiovascular diseases (CVDs). However, current methods and models of CVD do not include the factor of aging due to the use of premature cardiomyocytes. There is an urgent need for an engineered cardiovascular tissue (ECT) model that includes aging as the greatest CVD risk factor to facilitate drug development for aged CVD patients. Cell therapy, which transplants pluripotent stem cell-derived cardiomyocytes in patients, was proved to be effective for cardiac repair, while the cell retention rate is limited. Alternatively, implantation of ECT could enable long-term retention of cells after translation and may result in rejuvenation in aged hearts. This review summarizes the key features of aging and the influencing factors in engineered cardiovascular tissues. The applications and challenges of engineered myocardium designed for clinical use are also discussed.
Atrial fibrillation (AF) is the most common sustained arrhythmia, with a particularly high prevalence in the elderly. As the global aging population rapidly expands, it is increasingly important to examine how alterations to the aging heart contribute to an increased AF susceptibility. This work critically reviews the key molecular mechanisms that may underpin the complex association between aging and AF. Moreover, we identify emerging novel opportunities for therapeutic intervention that may be able to prevent and/or improve the current treatment paradigms for age-related AF. This review contributes to a holistic understanding of the intricate relationship between aging and AF.
Cardiovascular diseases (CVDs) and cancer are the two leading causes of global mortality. Cancer treatments, including radiotherapy and chemotherapy, can have severe cardiotoxic side effects, raising concerns for cancer patients and increasing the financial burden on healthcare systems. Recent studies have shown a link between cancer therapy-induced cardiotoxicity and cardiac senescence. Specifically, systemic cancer therapies are known to induce cardiac senescence, which may directly result in cardiac dysfunction or enhance the vulnerability of the heart to other stressors. Besides anthracyclines, newer, more targeted therapies such as tyrosine kinase inhibitors (TKIs) have also been shown to induce cardiac senescence. Cellular senescence is triggered by DNA damage, oncogene activation, reactive oxygen and nitrogen species, and other stressors, leading to the secretion of proinflammatory factors, increased oxidative stress, and disruption of normal cellular functions. Understanding the molecular mechanisms of cardiac senescence induced by cancer therapy is essential for attenuating or even preventing clinically overt cardiotoxicity using senotherapies such as senolytics and senomorphics. In this review, cancer therapies that are associated with CVDs are described with an emphasis on the potential role of cardiac senescence in the disease progression. In addition, the known mechanisms by which anthracyclines, particularly doxorubicin (DOX), radiotherapy, and TKIs lead to cardiac senescence are highlighted. Finally, recent and novel senotherapies for treating cellular senescence are discussed with a focus on targeting cardiac senescence following cancer treatment. The field remains in its early stages, with further research required to clarify how cancer treatments contribute to cardiotoxicity. At the same time, identifying senotherapies that can be safely combined with cancer drugs is essential for targeting cardiac senescence and protecting cardiac health in cancer patients.
This review discusses the pathophysiological changes associated with cardiac aging and the potential therapeutic role of the anti-aging protein Klotho. It highlights key contributors to heart failure, such as arterial stiffening, myocardial fibrosis, and impaired cardiac relaxation, all of which lead to the declining function of the aging heart. This review also explores the regulation of Klotho expression, its various forms, and its impact on cardiac health, emphasizing its protective roles against oxidative stress, inflammation, and cardiac remodeling. Klotho's potential as a therapeutic target for mitigating cardiac aging and improving cardiovascular health in the elderly is a central theme, making it a promising candidate for future interventions aimed at enhancing cardiac function and longevity.
The age-related decline in diastolic function can result in heart failure with a preserved ejection fraction (HFpEF) and atrial fibrillation (AF), which are comorbid conditions that are increasingly prevalent and have a high socioeconomic burden. In humans, diastolic dysfunction results from structural and functional changes that increasingly impede diastolic filling after midlife. Comorbidities and pathomechanisms that lead to additional increases in cardiac filling pressures accelerate the age-related deterioration in diastolic function. It is, therefore, that targeting the accelerators of diastolic dysfunction holds the most promise in reducing the risk for HFpEF and AF.
Acetyltransferases are enzymes that catalyze the transfer of an acetyl group to a substrate, a modification referred to as acetylation. Loss-of-function variants in genes encoding acetyltransferases can lead to congenital disorders, often characterized by intellectual disability and heart and muscle defects. Their activity is influenced by dietary nutrients that alter acetyl coenzyme A levels, a key cofactor. Cardiovascular diseases, including ischemic, hypertensive, and diabetic heart diseases - leading causes of mortality in the elderly - are largely attributed to prolonged lifespan and the growing prevalence of metabolic syndrome. Acetyltransferases thus serve as a crucial link between lifestyle modifications, cardiometabolic disease, and aging through both epigenomic and non-epigenomic mechanisms. In this review, we discuss the roles and relevance of acetyltransferases. While the sirtuin family of deacetylases has been extensively studied in longevity, particularly through fasting-mediated NAD+ metabolism, recent research has brought attention to the essential roles of acetyltransferases in health and aging-related pathways, including cell proliferation, DNA damage response, mitochondrial function, inflammation, and senescence. We begin with an overview of acetyltransferases, classifying them by domain structure, including canonical and non-canonical lysine acetyltransferases, N-terminal acetyltransferases, and sialic acid