Endothelial Cell Senescence Effect on the Blood-Brain Barrier in Stroke and Cognitive Impairment DOI

Maria Guadalupe C. Real,

Sarina Falcione, Roobina Boghozian

et al.

Neurology, Journal Year: 2024, Volume and Issue: 103(11)

Published: Nov. 14, 2024

Age is an important risk factor of stroke, cognitive decline, and dementia. Senescent endothelial cells (ECs) accumulate with advancing age through exposure to cellular stress, such as that exerted by hypertension diabetes. These senescent ECs have altered characteristics, tight junction proteins, use a more indiscriminate transcellular transport system, increased inflammation, immune cell interactions. are the main component blood-brain barrier (BBB), separating brain from systemic circulation. As in BBB, their functioning results disruption barrier. They inadequate barrier-forming properties, disrupted extracellular matrix, transcytosis, resulting overly permeable This BBB can effects stroke impairment, presented this review. Besides increasing permeability also impair angiogenesis vascular remodeling, which ischemic may increase hemorrhagic transformation worsen outcomes. contribute microvascular dysfunction, cerebral perfusion autoregulation. impairment along permeability. With aging population, there growing interest targeting senescence. Several ongoing trials been evaluating whether senolytics slow aging, improve health, reduce decline.

Language: Английский

Molecular mechanisms of aging and anti-aging strategies DOI Creative Commons
Yumeng Li,

Xutong Tian,

Juyue Luo

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 24, 2024

Abstract Aging is a complex and multifaceted process involving variety of interrelated molecular mechanisms cellular systems. Phenotypically, the biological aging accompanied by gradual loss function systemic deterioration multiple tissues, resulting in susceptibility to aging-related diseases. Emerging evidence suggests that closely associated with telomere attrition, DNA damage, mitochondrial dysfunction, nicotinamide adenine dinucleotide levels, impaired macro-autophagy, stem cell exhaustion, inflammation, protein balance, deregulated nutrient sensing, altered intercellular communication, dysbiosis. These age-related changes may be alleviated intervention strategies, such as calorie restriction, improved sleep quality, enhanced physical activity, targeted longevity genes. In this review, we summarise key historical progress exploration important causes anti-aging strategies recent decades, which provides basis for further understanding reversibility phenotypes, application prospect synthetic biotechnology therapy also prospected.

Language: Английский

Citations

53
Sex-specific mechanisms in vascular aging: exploring cellular and molecular pathways in the pathogenesis of age-related cardiovascular and cerebrovascular diseases DOI Creative Commons
Anna Ungvari, Rafał Gulej, Roland Patai

et al.

GeroScience, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Language: Английский

Citations

3
Intermittent supplementation with fisetin improves arterial function in old mice by decreasing cellular senescence DOI Creative Commons
Sophia Mahoney,

Ravinandan Venkatasubramanian,

Mary A. Darrah

et al.

Aging Cell, Journal Year: 2023, Volume and Issue: 23(3)

Published: Dec. 7, 2023

Abstract Cellular senescence and the senescence‐associated secretory phenotype (SASP) contribute to age‐related arterial dysfunction, in part, by promoting oxidative stress inflammation, which reduce bioavailability of vasodilatory molecule nitric oxide (NO). In present study, we assessed efficacy fisetin, a natural compound, as senolytic vascular cell SASP factors improve function old mice. We found that fisetin decreased cellular human endothelial culture. mice, SASP‐related inflammation were lower 1 week after final dose oral intermittent (1 on—2 weeks off—1 on dosing) supplementation. Old fisetin‐supplemented mice had higher function. Leveraging p16‐3MR transgenic model allowing genetic clearance p16 INK4A ‐positive senescent cells, ex vivo removal cells from arteries isolated vehicle‐ but not fisetin‐treated increased endothelium‐dependent dilation, demonstrating improved through senolysis. Enhanced with was mediated NO reduced cellular‐ mitochondrial‐related stress. Arterial stiffness Ex senolysis aorta rings did further mechanical wall due Lower accompanied favorable remodeling. The findings this study identify promising therapy for clinical translation target excess treat dysfunction.

Language: Английский

Citations

39
Nanocarriers for natural polyphenol senotherapeutics DOI Creative Commons
Natali Joma,

Patrick‐Brian Bielawski,

Anjali Saini

et al.

Aging Cell, Journal Year: 2024, Volume and Issue: 23(5)

Published: April 29, 2024

Abstract Senescence is a heterogenous and dynamic process in which various cell types undergo cell‐cycle arrest due to cellular stressors. While senescence has been implicated aging many human pathologies, therapeutic interventions remain inadequate the absence of comprehensive set biomarkers context‐dependent manner. Polyphenols have investigated as senotherapeutics both preclinical clinical settings. However, their use hindered by limited stability, toxicity, modest bioavailability, often concentration at target sites. To address these limitations, nanocarriers such polymer nanoparticles lipid vesicles can be utilized enhance efficacy senolytic polyphenols. Focusing on widely studied agents—specifically fisetin, quercetin, resveratrol—we provide concise summaries physical chemical properties, along with an overview findings. We also highlight common signaling pathways potential toxicities associated agents. Addressing challenges linked nanocarriers, we present examples senotherapeutic delivery types, without nanocarriers. Finally, continued research development agents are encouraged reduce undesirable effects different organs. This review underscores need for establishing reliable sets that could assist evaluating effectiveness current future candidates

Language: Английский

Citations

13
Accelerated Aging Induced by an Unhealthy High-Fat Diet: Initial Evidence for the Role of Nrf2 Deficiency and Impaired Stress Resilience in Cellular Senescence DOI Open Access
Priya Balasubramanian, Tamás Kiss, Rafał Gulej

et al.

Nutrients, Journal Year: 2024, Volume and Issue: 16(7), P. 952 - 952

Published: March 26, 2024

High-fat diets (HFDs) have pervaded modern dietary habits, characterized by their excessive saturated fat content and low nutritional value. Epidemiological studies compellingly linked HFD consumption to obesity the development of type 2 diabetes mellitus. Moreover, synergistic interplay HFD, obesity, expedites aging process prematurely fosters age-related diseases. However, underlying mechanisms driving these associations remain enigmatic. One most conspicuous hallmarks is accumulation highly inflammatory senescent cells, with mounting evidence implicating increased cellular senescence in pathogenesis Our hypothesis posits that amplifies burden across multiple organs. To scrutinize this hypothesis, we subjected mice a 6-month regimen, assessing biomarker expression liver, white adipose tissue, brain. Aging intrinsically impaired stress resilience, driven dysfunction Nrf2-mediated cytoprotective pathways safeguard cells against oxidative stress-induced senescence. ascertain whether shield induction response consumption, explored novel model aging: Nrf2-deficient (Nrf2+/−) mice, emulating phenotype. initial findings unveiled significant Nrf2 Nrf2+/− mirroring aging-related alterations. led substantial hyperglycemia, insulin sensitivity both Nrf2+/+ mice. In control primarily heightened evidenced Cdkn2a expression. elicited surge We postulate HFD-induced augmentation may be pivotal contributor accelerated organismal premature onset

Language: Английский

Citations

10
Elucidating emerging signaling pathways driving endothelial dysfunction in cardiovascular aging DOI

Anna De Bartolo,

Tommaso Angelone, Carmine Rocca

et al.

Vascular Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 107462 - 107462

Published: Jan. 1, 2025

Language: Английский

Citations

1
The senolytic ABT-263 improves cognitive functions in middle-aged male, but not female, atherosclerotic LDLr−/−;hApoB100+/+ mice DOI Creative Commons
Mélanie Lambert,

Géraldine Miquel,

Louis Villeneuve

et al.

GeroScience, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

Language: Английский

Citations

1
Socioeconomic status as a potential mediator of arterial aging in marginalized ethnic and racial groups: current understandings and future directions DOI
Sanna Darvish, Sophia Mahoney,

Ravinandan Venkatasubramanian

et al.

Journal of Applied Physiology, Journal Year: 2024, Volume and Issue: 137(1), P. 194 - 222

Published: May 30, 2024

Cardiovascular diseases (CVDs) are the leading cause of death in United States. However, disparities CVD-related morbidity and mortality exist as marginalized racial ethnic groups generally at higher risk for CVDs (Black Americans, Indigenous People, South Southeast Asians, Native Hawaiians, Pacific Islanders) and/or development traditional CVD factors (groups above plus Hispanics/Latinos) relative to non-Hispanic Whites (NHW). In this comprehensive review, we outline emerging evidence suggesting these experience accelerated arterial dysfunction, including vascular endothelial dysfunction large elastic artery stiffening, a nontraditional factor that may predict with advancing age. Adverse exposures social determinants health (SDOH), specifically lower socioeconomic status (SES), exacerbated most (except Asians—higher SES) be potential mediator aging. SES negatively influences ability meet aerobic exercise guidelines, first-line strategy improve function, due increased barriers, such time financial constraints, lack motivation, facility access, education, performing conventional exercise. Thus, identifying alternative interventions 1) overcome common barriers 2) target biological mechanisms aging function an effective, method ameliorate reduce risk. Importantly, dedicated efforts needed assess strategies randomized-controlled clinical trials groups.

Language: Английский

Citations

5
Cellular Senescence and Cardiovascular Aging DOI

Dharmesh Kapoor,

Imteyaz Qamar

Published: Jan. 1, 2025

Citations

0
A new clinical age of aging research DOI Creative Commons
Zhen Zhang, Renlei Yang, Zhike Zi

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Aging is a major risk factor for variety of diseases, thus, translation aging research into practical applications driven by the unmet need existing clinical therapeutic options. Basic and translational efforts are converging at critical stage, yielding insights how fundamental mechanisms used to identify promising geroprotectors or therapeutics. This review highlights several areas from perspective, including senescent cell targeting, alleviation inflammaging, optimization metabolism with endogenous metabolites precursors. Refining our understanding these key areas, especially angle, may help us better understand attenuate processes improve overall health outcomes.

Language: Английский

Citations

4