Mechanisms of cellular senescence-induced vascular aging: evidence of senotherapeutic strategies DOI Open Access
Sophia Mahoney, Samuel I. Bloom,

Douglas R. Seals

et al.

The Journal of Cardiovascular Aging, Journal Year: 2025, Volume and Issue: 5(1)

Published: March 20, 2025

Cardiovascular diseases (CVD) remain the leading cause of death worldwide, with advancing age being primary, nonmodifiable risk factor. Vascular dysfunction, namely arterial stiffening and endothelial is key antecedent to development clinical CVD aging. Fundamental aging macro-mechanistic processes that drive vascular include excess oxidative stress, chronic inflammation, declines in vasodilatory molecule nitric oxide. An important hallmark contributes cellular senescence - a stress response characterized by cell cycle arrest accompanied production secretion proinflammatory molecules (i.e., senescence-associated secretory phenotype [SASP]). Excess senescent cells SASP have deleterious effects on function states CVD, making it putative therapeutic target for improving preventing or reversing CVD. This review will focus role age-related dysfunction We examine established emerging mechanisms underlying senescence-induced dysfunction. then discuss groups impaired high burden strategies reduce remove who are likely benefit most from these therapies. Finally, we highlight systemic suppression other tissues organs, given integrative vasculature physiology. Together, this underscore imperative need deeper understanding translational use targeting therapies burden.

Language: Английский

Emerging role of senescent microglia in brain aging-related neurodegenerative diseases DOI Creative Commons
Chan Rim, Min-Jung You, Minyeop Nahm

et al.

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Feb. 20, 2024

Abstract Brain aging is a recognized risk factor for neurodegenerative diseases like Alzheimer's disease, Parkinson's and amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), but the intricate interplay between brain pathogenesis of these conditions remains inadequately understood. Cellular senescence considered to contribute cellular dysfunction inflammaging. According threshold theory senescent cell accumulation, vulnerability associated with rates generation clearance within brain. Given role microglia in eliminating cells, accumulation may lead acceleration aging, contributing inflammaging increased diseases. In this review, we propose idea that microglia, which notably vulnerable could potentially serve as central catalyst progression The are emerging promising target mitigating

Language: Английский

Citations

36
Factors and Pathways Modulating Endothelial Cell Senescence in Vascular Aging DOI Open Access
Hyun Jung Hwang, Nayeon Kim, Allison B. Herman

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(17), P. 10135 - 10135

Published: Sept. 4, 2022

Aging causes a progressive decline in the structure and function of organs. With advancing age, an accumulation senescent endothelial cells (ECs) contributes to risk developing vascular dysfunction cardiovascular diseases, including hypertension, diabetes, atherosclerosis, neurodegeneration. Senescent ECs undergo phenotypic changes that alter pattern expressed proteins, as well their morphologies functions, have been linked impairments, such aortic stiffness, enhanced inflammation, dysregulated tone. Numerous molecules pathways, sirtuins, Klotho, RAAS, IGFBP, NRF2, mTOR, implicated promoting EC senescence. This review summarizes molecular players signaling pathways driving senescence identifies targets with possible therapeutic value age-related diseases.

Language: Английский

Citations

53
The relationship between the pan-immune-inflammation value and long-term prognoses in patients with hypertension: National Health and Nutrition Examination Study, 1999–2018 DOI Creative Commons

Bo Wu,

Chenlu Zhang,

Shuqiong Lin

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2023, Volume and Issue: 10

Published: March 2, 2023

Direct antihypertensive therapy in hypertensive patients with a high CVD risk can reduce the incidence of cardiovascular death but increase adverse events, so additional ways to identify at may be needed. Studies have shown that immunity and inflammation affect prognoses hypertension pan-immune-inflammation value (PIV) is an index assess inflammation, few studies applied PIV hypertension.To explore relationship between long-term all-cause mortality hypertension.Data from National Health Nutrition Examination Survey (NHANES) 1999-2018 follow-up through December 31, 2019, were analyzed. A total 26,781 participants evaluated. The grouped based on levels as follows: T1 group (n = 8,938), T2 8,893), T3 8,950). was assessed by survival curves Cox regression analysis NHANES recommended weights.The significantly associated hypertension. After full adjustment, higher [Group 3: HR: 1.37, 95% CI: 1.20-1.55, p < 0.001] 1.62, 1.22-2.15, mortality.Elevated increased patients.

Language: Английский

Citations

32
Endothelial Senescence: From Macro- to Micro-Vasculature and Its Implications on Cardiovascular Health DOI Open Access

Peichun Wang,

Daniels Konja, Sandeep Singh

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 1978 - 1978

Published: Feb. 6, 2024

Endothelial cells line at the most inner layer of blood vessels. They act to control hemostasis, arterial tone/reactivity, wound healing, tissue oxygen, and nutrient supply. With age, endothelial become senescent, characterized by reduced regeneration capacity, inflammation, abnormal secretory profile. senescence represents one earliest features ageing contributes many age-related diseases. Compared those in arteries veins, microcirculation exhibit a greater extent heterogeneity. Microcirculatory leads declined capillary density, angiogenic potentials, decreased flow, impaired barrier properties, hypoperfusion or organ-dependent manner. The heterogeneous phenotypes microvascular particular vascular bed across different tissues remain largely unknown. Accordingly, mechanisms underlying macro- micro-vascular vary pathophysiological conditions, thus offering specific target(s) for therapeutic development senolytic drugs.

Language: Английский

Citations

16
Understanding the intricacies of cellular senescence in atherosclerosis: Mechanisms and therapeutic implications DOI Creative Commons
Ilyas Ali, Hongliang Zhang, Syed Aqib Ali Zaidi

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 96, P. 102273 - 102273

Published: March 14, 2024

Language: Английский

Citations

11
Proteostasis disruption and senescence in Alzheimer’s disease pathways to neurodegeneration DOI
Riya Thapa, Asif Ahmad Bhat, Moyad Shahwan

et al.

Brain Research, Journal Year: 2024, Volume and Issue: 1845, P. 149202 - 149202

Published: Aug. 30, 2024

Language: Английский

Citations

9
Senescence-Associated Secretory Phenotype of Cardiovascular System Cells and Inflammaging: Perspectives of Peptide Regulation DOI Creative Commons
Khavinson VKh, N. S. Linkova, Anastasiia Dyatlova

et al.

Cells, Journal Year: 2022, Volume and Issue: 12(1), P. 106 - 106

Published: Dec. 27, 2022

A senescence-associated secretory phenotype (SASP) and a mild inflammatory response characteristic of senescent cells (inflammaging) form the conditions for development cardiovascular diseases: atherosclerosis, coronary heart disease, myocardial infarction. The purpose review is to analyze pool signaling molecules that SASP inflammaging in system search targets action vasoprotective peptides. characterized by change synthesis anti-proliferative proteins (p16, p19, p21, p38, p53), cytokines (IL-1α,β, IL-4, IL-6, IL-8, IL-18, TNFα, TGFβ1, NF-κB, MCP), matrix metalloproteinases, adhesion molecules, sirtuins. It has been established peptides are physiological regulators body functions. Vasoprotective polypeptides (liraglutide, atrial natriuretic peptide, mimetics relaxin, Ucn1, adropin), KED tripeptide, AEDR tetrapeptide regulate involved SASP-forming system. This indicates prospects drugs based on treatment age-associated pathology.

Language: Английский

Citations

30
“Bone-SASP” in Skeletal Aging DOI Creative Commons

Ching‐Lien Fang,

Bin Liu, Mei Wan

et al.

Calcified Tissue International, Journal Year: 2023, Volume and Issue: 113(1), P. 68 - 82

Published: May 31, 2023

Abstract Senescence is a complex cell state characterized by stable cycle arrest and unique secretory pattern known as the senescence-associated phenotype (SASP). The SASP factors, which are heterogeneous tissue specific, normally include chemokines, cytokines, growth adhesion molecules, lipid components that can lead to multiple age-associated disorders eliciting local systemic consequences. skeleton highly dynamic organ changes constantly in shape composition. Senescent cells bone marrow produce diverse factors induce alterations of through paracrine effects. Herein, we refer cell-associated “bone-SASP.” In this review, describe current knowledge cellular senescence SASP, focusing on role senescent mediating pathologies during natural aging premature syndromes. We also summarize bone-SASP glucocorticoids-induced damage. addition, discuss development osteoarthritis, highlighting mechanisms drives subchondral metabolic syndrome-associated osteoarthritis.

Language: Английский

Citations

21
Senescent Microglia Represent a Subset of Disease-Associated Microglia in P301S Mice DOI
Pei Ying Ng, Cheng Zhang, Hu Li

et al.

Journal of Alzheimer s Disease, Journal Year: 2023, Volume and Issue: 95(2), P. 493 - 507

Published: Aug. 4, 2023

Background: The existence and contribution of microglia with senescent-like alterations in the pathogenesis age-related neurodegenerative diseases like Alzheimer’s disease (AD) have been suggested recent years. However, identification this distinct microglial population vivo has proven challenging, largely due to overlaps inflammatory phenotype activated senescent microglia. Furthermore, attempts at recapitulating senescence vitro are limited. Objective: To identify characterize that occur an animal model neurodegeneration driven by pathologic tau. Methods: We analyzed RNA expression patterns individual from normal mice pathogenic tau P301 S PS19 mouse model. previously demonstrated p16-expressing these when occurred. Results: Here we a subset disease-associated features, notably characterized Ccl4. This signature established markers other cell types. Conclusion: Our characterization can be used better understand role various contexts, including whether clearance represents viable therapeutic option.

Language: Английский

Citations

19
Colchicine prevents oxidative stress-induced endothelial cell senescence via blocking NF-κB and MAPKs: implications in vascular diseases DOI Creative Commons
Huakang Zhou, Dilaware Khan,

Sajid Muhammad Hussain

et al.

Journal of Inflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: Nov. 24, 2023

Smoking, alcohol abuse, and hypertension are - among others, potential risk factors for cardiovascular diseases. These generate oxidative stress cause stress-induced DNA damage, resulting in cellular senescence senescence-associated secretory phenotype (SASP). The SASP feed-forward response exacerbate inflammation tissue remodeling, atherosclerotic plaque formation rupture.Colchicine inhibited ROS generation mitigated damage. It dampened endothelial cell improved the expression of repair protein KU80 aging marker Lamin B1. drug attenuated P21 at mRNA levels. pathway analysis showed that colchicine NF-κB MAPKs pathways subdued mTOR activation. Colchicine also interleukin (IL)-1β, IL-6, IL-8, MCP-1, ICAM-1, E-selectin. Furthermore, reduced matrix metalloproteinase (MMP-2).In summary, blocked by inhibiting activation pathways.

Language: Английский

Citations

18