Cardiovascular aging: from cellular and molecular changes to therapeutic interventions

Vakka, Angeliki; Warren, Jason G.; Drosatos, Konstantinos

doi:10.20517/jca.2023.09

Cited by 7 publications

(5 citation statements)

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“…It is well known that the aging heart is associated with increased cardiomyocyte apoptosis, chronic inflammation, oxidative stress, and cardiac fibrosis ( Vakka et al, 2023 ). In the current study, we observe that arg-ii -/- mice are protected from cardiac aging phenotype and reveal a decrease in apoptotic cells, particularly cardiomyocytes but also non-cardiomyocytes.…”

Section: Discussionmentioning

confidence: 99%

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Cell-autonomous and non-cell-autonomous effects of arginase-II on cardiac aging

Potenza,

Cheng,

Ajalbert

et al. 2024

Preprint

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Aging is a predominant risk factor for heart disease. Aging heart reveals low-grade chronic inflammation, cell apoptosis, cardiac fibrosis, and increased vulnerability to ischemic injury. The underlying molecular mechanisms responsible for the cardiac aging phenotype and its susceptibility to injury are far from being fully understood. Although previous literature reports a role of the mitochondrial enzyme arginase-II (Arg-II) in development of heart failure, contradictory results are reported and no systematic analysis of cellular expression and localization of Arg-II in the heart has been performed. Whether and how Arg-II participates in cardiac aging are still unknown. In this study, we demonstrate, to our surprise, that Arg-II is not expressed in cardiomyocytes from aged mice and human patients, but upregulated in non-myocytes of the aging heart, including macrophages, fibroblasts, endothelial cells. Mice with genetic deficiency of arg-ii (arg-ii-/-) are protected from age-associated cardiac inflammation, myocyte apoptosis, interstitial and perivascular fibrosis, endothelial-mesenchymal transition (EndMT), and susceptibility to ischemic injury. Further experiments show that Arg-II mediates IL-1beta release from macrophages of old mice, contributing to the above-described cardiac aging phenotype. In addition, Arg-II enhances mitochondrial reactive oxygen species (mtROS) and activates cardiac fibroblasts that is inhibited by inhibition of mtROS. Thus, our study demonstrates a non-cell-autonomous effect of Arg-II on cardiomyocytes, fibroblasts, and endothelial cells mediated by IL-1b from aging macrophages as well as a cell-autonomous effect of Arg-II through mtROS in fibroblasts contributing to cardiac aging phenotype.

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Section: Discussionmentioning

confidence: 99%

“…It is well known that the aging heart is associated with increased cardiomyocyte apoptosis, chronic inflammation, oxidative stress, and cardiac fibrosis (Vakka et al, 2023). In the current study, we observe that arg-ii One of the important features of cardiac aging is fibrosis which is due to chronic inflammation process (Lu et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Cell-autonomous and non-cell-autonomous effects of arginase-II on cardiac aging

Potenza,

Cheng,

Ajalbert

et al. 2024

Preprint

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“…To account for and understand the molecular events underlying the etiology of HCM, we hereinafter only consider the key biochemical cascades triggered by either gene mutation or age. Systematic reviews published on the genetic basis and the role of aging in HCM are excellent resources for gaining further perspectives [ 49 , 50 ] .…”

Section: Aging As a Risk Factor For Hcmmentioning

confidence: 99%

“…A systematic compilation of age-associated molecular changes in cardiovascular function has been recently published [ 50 ] . A close look at HCM pathogenetic mechanisms reveals that HCM processes are congruent with those of aging since they share some common hallmarks [ Figure 3 ].…”

Section: Association Of Mybpc3 Variants Aging and ...mentioning

confidence: 99%

Hypertrophic cardiomyopathy in MYBPC3 carriers in aging

Ananthamohan,

Stelzer,

Sadayappan

2024

J Cardiovasc Aging

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Hypertrophic cardiomyopathy (HCM) is characterized by abnormal thickening of the myocardium, leading to arrhythmias, heart failure, and elevated risk of sudden cardiac death, particularly among the young. This inherited disease is predominantly caused by mutations in sarcomeric genes, among which those in the cardiac myosin binding protein-C3 (MYBPC3 ) gene are major contributors. HCM associated with MYBPC3 mutations usually presents in the elderly and ranges from asymptomatic to symptomatic forms, affecting numerous cardiac functions and presenting significant health risks with a spectrum of clinical manifestations. Regulation of MYBPC3 expression involves various transcriptional and translational mechanisms, yet the destiny of mutant MYBPC3 mRNA and protein in late-onset HCM remains unclear. Pathogenesis related to MYBPC3 mutations includes nonsense-mediated decay, alternative splicing, and ubiquitin-proteasome system events, leading to allelic imbalance and haploinsufficiency. Aging further exacerbates the severity of HCM in carriers of MYBPC3 mutations. Advancements in high-throughput omics techniques have identified crucial molecular events and regulatory disruptions in cardiomyocytes expressing MYBPC3 variants. This review assesses the pathogenic mechanisms that promote late-onset HCM through the lens of transcriptional, post-transcriptional, and post-translational modulation of MYBPC3 , underscoring its significance in HCM across carriers. The review also evaluates the influence of aging on these processes and MYBPC3 levels during HCM pathogenesis in the elderly. While pinpointing targets for novel medical interventions to conserve cardiac function remains challenging, the emergence of personalized omics offers promising avenues for future HCM treatments, particularly for late-onset cases.

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“…The increase in older aged population is anticipated to result in significant socioeconomic and health care problems as aging predisposes to several chronic diseases that can cause disability and dependency. Advancing age is not only related to increased cognitive decline and dementia ( 2 ) but also with depression ( 3 ) and cardiovascular events ( 4 ). Nonetheless, some individuals age successfully, preserving physical, physiological and cognitive functions as well as sustaining emotional wellbeing ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Lifestyle trajectories in middle-aged adults and their relationship with health indicators

Roca-Ventura,

Solana-Sánchez,

Cattaneo

et al. 2024

Front. Public Health

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IntroductionUnderstanding the impact of different lifestyle trajectories on health preservation and disease risk is crucial for effective interventions.MethodsThis study analyzed lifestyle engagement over five years in 3,013 healthy adults aged 40-70 from the Barcelona Brain Health Initiative using K-means clustering. Nine modifiable risk factors were considered, including cognitive, physical, and social activity, vital plan, diet, obesity, smoking, alcohol consumption, and sleep. Self-reported diagnoses of new diseases at different time-points after baseline allowed to explore the association between these five profiles and health outcomes.ResultsThe data-driven analysis classified subjects into five lifestyle profiles, revealing associations with health behaviors and risk factors. Those exhibiting high scores in health-promoting behaviors and low-risk behaviors, demonstrate a reduced likelihood of developing diseases (p < 0.001). In contrast, profiles with risky habits showed distinct risks for psychiatric, neurological, and cardiovascular diseases. Participant’s lifestyle trajectories remained relatively stable over time.DiscussionOur findings have identified risk for distinct diseases associated to specific lifestyle patterns. These results could help in the personalization of interventions based on data-driven observation of behavioral patterns and policies that promote a healthy lifestyle and can lead to better health outcomes for people in an aging society.

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Cardiovascular aging: from cellular and molecular changes to therapeutic interventions

Cited by 7 publications

References 229 publications

Cell-autonomous and non-cell-autonomous effects of arginase-II on cardiac aging

Cell-autonomous and non-cell-autonomous effects of arginase-II on cardiac aging

Hypertrophic cardiomyopathy in MYBPC3 carriers in aging

Lifestyle trajectories in middle-aged adults and their relationship with health indicators

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