Interconnected Pathways and Therapeutic Implications for Cardiovascular Aging and Diseases

Figures

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  Figure 1. Aging-Related Changes in the Cardiovascular System At the organ/tissue level, cardiac aging manifests as ventricular hypertrophy, enhanced valvular calcification, and myocardial fibrosis, whereas arterial aging presents with intimal thickening, vessel wall thickening, and luminal dilation. These macroscopic alterations arise from cellular changes (including accumulation of senescent cells, phenotypic transitions in cardiovascular cells, and excessive cell death) and molecular-level abnormalities, including metabolic dysfunction (impaired nutrient sensing and mitochondrial dysfunction), genomic and epigenomic instability, proteostasis dysregulation, and inflammatory responses. CVA = cardiovascular aging; GFs = growth factors; ROS = reactive oxygen species.

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  Figure 2. Hallmarks for CVA and CVDs Biomarkers of CVA demonstrate overlap with established clinical diagnostic markers for cardiovascular diseases (CVDs), including B-type natriuretic peptide (BNP), Angiotensin II, Endothelin-1, levels of ROS, matrix metalloproteinase (MMP), pulse wave velocity (PWV), and carotid intima-media thickness (cIMT). These parameters can be assessed through noninvasive or minimally invasive methodologies, offering promising potential for facilitating early detection and preventive intervention strategies for CVDs in geriatric populations. IGF-1 = insulin-like growth factor 1; MI = myocardial infarction; VEC = vascular endothelial cell; VHD = valvular heart disease; other abbreviations as in Figure 1.

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  Figure 3. Addressing CVDs Through Strategies for CVA Interventions Aging-targeted therapeutic modalities, encompassing compounds, gene therapies, and cellular therapeutics, alongside lifestyle modifications such as caloric restriction (CR), intermittent fasting (IF), and structured physical activity regimens, demonstrate efficacy in ameliorating cardiovascular degenerative processes. GLP-1 RA = glucagon-like protein 1 receptor agonist; MCO = 3D mini-cardiac organoid; MitoQ = mitochondrial-targeted coenzyme Q10; NKG2D-CAR T = natural killer group 2 member D-targeted chimeric antigen receptor T cells; NMN = β-nicotinamide mononucleotide; PGC-1α = peroxisome proliferator-activated receptor gamma coactivator 1-alpha; SIRT1 = NAD+-dependent deacetylase sirtuin-1; SIRT2 = NAD+-dependent deacetylase sirtuin-2; SRCs = senescence-resistant human mesenchymal progenitor cells.

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  Central Illustration. Pathophysiological Convergence Between Cardiovascular Aging and Cardiovascular Diseases CVA and age-related CVDs share structural and functional alterations, as well as convergent mechanisms at the tissue, cellular, and molecular levels, resulting in overlapping biomarker profiles. Interventions that target CVA have shown promising preventive and therapeutic benefits for CVDs in diverse models, indicating that approaches aimed at slowing or reversing aging are making the prevention and treatment of age-related CVDs increasingly attainable clinical goals. BNP = B-type natriuretic peptide; cIMT = carotid intima-media thickness; CR = caloric restriction; CVA = cardiovascular aging; CVDs = cardiovascular diseases; GLP-1 RA = glucagon-like peptide-1 receptor agonist; IF = intermittent fasting; IGF-1 = insulin-like growth factor-1; MCOs = 3D mini-cardiac organoids; MitoQ = mitochondrial-targeted coenzyme Q10; NKG2D-CAR T = natural killer group 2 member D-targeted chimeric antigen receptor T cells; NMN = β-nicotinamide mononucleotide; PGC-1α = peroxisome proliferator-activated receptor gamma coactivator 1-alpha; PWV = pulse wave velocity; SIRT1 = NAD+-dependent deacetylase sirtuin-1;…