Senolysis-Based Elimination of Chemotherapy-Induced Senescent Breast Cancer Cells by Quercetin Derivative with Blocked Hydroxy Groups DOI Open Access
Anna Lewińska, Paweł Przybylski, Jagoda Adamczyk‐Grochala

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(3), P. 605 - 605

Published: Jan. 25, 2022

Drug-induced senescence program may be activated both in normal and cancer cells as a consequence of chemotherapeutic treatment, leading to some adverse side effects such senescence-associated secretory phenotype (SASP), secondary senescence, promotion. Targeted elimination senescent can achieved by drugs with senolytic activity (senolytics), for example, the plant-derived natural compound quercetin, especially when co-treated kinase inhibitor dasatinib. In present study, three quercetin derivatives were synthesized tested improved action against etoposide-induced human mammary epithelial triple-negative breast vitro. Transformation catechol moiety into diphenylmethylene ketal addition acetyl groups molecule (QD3 derivative) promoted clearance judged increased apoptosis compared etoposide-treated cells. A QD3-mediated effect was accompanied decreased SA-beta galactosidase levels p27, IL-1β, IL-8, HSP70 Similar not observed conclusion, novel agent QD3 described acting Thus, new one-two punch anti-cancer strategy based on combined pro-senescence drug is proposed.

Language: Английский

Cellular senescence: a key therapeutic target in aging and diseases DOI Creative Commons
Lei Zhang,

Louise E. Pitcher,

Matthew J. Yousefzadeh

et al.

Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 132(15)

Published: July 31, 2022

Cellular senescence is a hallmark of aging defined by stable exit from the cell cycle in response to cellular damage and stress. Senescent cells (SnCs) can develop characteristic pathogenic senescence-associated secretory phenotype (SASP) that drives secondary disrupts tissue homeostasis, resulting loss repair regeneration. The use transgenic mouse models which SnCs be genetically ablated has established key role for driving age-related disease. Importantly, senotherapeutics have been developed pharmacologically eliminate SnCs, termed senolytics, or suppress SASP other markers senescence, senomorphics. Based on extensive preclinical studies as well small clinical trials demonstrating benefits senotherapeutics, multiple are under way. This Review discusses diseases, strategies target approaches discover advances senolytics.

Language: Английский

Citations

331
The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice DOI Creative Commons

Qixia Xu,

Qiang Fu, Zi Li

et al.

Nature Metabolism, Journal Year: 2021, Volume and Issue: 3(12), P. 1706 - 1726

Published: Dec. 6, 2021

Abstract Ageing-associated functional decline of organs and increased risk for age-related chronic pathologies is driven in part by the accumulation senescent cells, which develop senescence-associated secretory phenotype (SASP). Here we show that procyanidin C1 (PCC1), a polyphenolic component grape seed extract (GSE), increases healthspan lifespan mice through its action on cells. By screening library natural products, find GSE, PCC1 as one active components, have specific effects At low concentrations, appears to inhibit SASP formation, whereas it selectively kills cells at higher possibly promoting production reactive oxygen species mitochondrial dysfunction. In rodent models, depletes treatment-damaged tumour microenvironment enhances therapeutic efficacy when co-administered with chemotherapy. Intermittent administration either irradiated, cell-implanted or naturally aged old alleviates physical dysfunction prolongs survival. We identify senotherapeutic agent vivo activity high potential further development clinical intervention delay, alleviate prevent pathologies.

Language: Английский

Citations

215
Skin Aging, Cellular Senescence and Natural Polyphenols DOI Open Access

Erika Csekes,

Lucia Račková

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(23), P. 12641 - 12641

Published: Nov. 23, 2021

The skin, being the barrier organ of body, is constitutively exposed to various stimuli impacting its morphology and function. Senescent cells have been found accumulate with age may contribute age-related skin changes pathologies. Natural polyphenols exert many health benefits, including ameliorative effects on aging. By affecting molecular pathways senescence, are able prevent or delay senescence formation and, consequently, avoid ameliorate aging age-associated pathologies skin. This review aims provide an overview current state knowledge in cellular summarize recent vitro studies related anti-senescent mechanisms natural carried out keratinocytes, melanocytes fibroblasts. Aged context COVID-19 pandemic will be also discussed.

Language: Английский

Citations

206
Targeting aging mechanisms: pharmacological perspectives DOI
Alexey Moskalev,

Zulfiya G. Guvatova,

Inês de Almeida Lopes

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2022, Volume and Issue: 33(4), P. 266 - 280

Published: Feb. 17, 2022

Language: Английский

Citations

104
Cellular senescence in lung cancer: Molecular mechanisms and therapeutic interventions DOI Creative Commons
Saurav Kumar Jha, Gabriele De Rubis, Shankar Raj Devkota

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 97, P. 102315 - 102315

Published: April 26, 2024

Lung cancer stands as the primary contributor to cancer-related fatalities worldwide, affecting both genders. Two types exist where non-small cell lung (NSCLC), accounts for 80–85% and SCLC 10-15% of cases. NSCLC subtypes include adenocarcinoma, squamous carcinoma, large carcinoma. Smoking, second-hand smoke, radon gas, asbestos, other pollutants, genetic predisposition, COPD are risk factors. On hand, stresses such DNA damage, telomere shortening, oncogene activation cause a prolonged cycle halt, known senescence. Despite its initial role tumor-suppressing mechanism that slows growth, excessive or improper control this process can age-related diseases, including cancer. Cellular senescence has two purposes in Researchers report tumor growth by constraining multiplication impaired cells. However, senescent cells also demonstrate pro-inflammatory senescence-associated secretory phenotype (SASP), which is widely reported promote This review will look at cellular cancer, describe diagnostic markers, ask about current treatments it, case studies clinical trials show how senescence-targeting therapies be used talk problems currently being faced, possible solutions same future.

Language: Английский

Citations

36
Recent Advances in Magnetite Nanoparticle Functionalization for Nanomedicine DOI Creative Commons

Roxana Cristina Popescu,

Ecaterina Andronescu, Bogdan Ștefan Vasile

et al.

Nanomaterials, Journal Year: 2019, Volume and Issue: 9(12), P. 1791 - 1791

Published: Dec. 16, 2019

Functionalization of nanomaterials can enhance and modulate their properties behaviour, enabling characteristics suitable for medical applications. Magnetite (Fe3O4) nanoparticles are one the most popular types used in this field, many technologies being already translated clinical practice. This article makes a summary surface modification functionalization approaches presented lately scientific literature improving or modulating magnetite applications nanomedicine.

Language: Английский

Citations

103
Flavonoids in Skin Senescence Prevention and Treatment DOI Open Access
Anna Domaszewska-Szostek, Monika Puzianowska‐Kuźnicka, Alina Kuryłowicz

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(13), P. 6814 - 6814

Published: June 25, 2021

Skin aging is associated with the accumulation of senescent cells and related to many pathological changes, including decreased protection against pathogens, increased susceptibility irritation, delayed wound healing, cancer susceptibility. Senescent secrete a specific set pro-inflammatory mediators, referred as senescence-associated secretory phenotype (SASP), which can cause profound changes in tissue structure function. Thus, drugs that selectively eliminate (senolytics) or neutralize SASP (senostatics) represent an attractive therapeutic strategy for age-associated skin deterioration. There growing evidence plant-derived compounds (flavonoids) slow down even prevent aging-associated deterioration appearance function by targeting cellular pathways crucial regulating senescence SASP. This review summarizes senostatic senolytic potential flavonoids context preventing aging.

Language: Английский

Citations

95
Microbiome and Human Aging: Probiotic and Prebiotic Potentials in Longevity, Skin Health and Cellular Senescence DOI Open Access
Jacqueline L. Boyajian, Merry Ghebretatios, Sabrina Schaly

et al.

Nutrients, Journal Year: 2021, Volume and Issue: 13(12), P. 4550 - 4550

Published: Dec. 18, 2021

The role of the microbiome in human aging is important: directly impacts through gastrointestinal system. However, microbial impact on skin has yet to be fully understood. For example, cellular senescence an intrinsic process that been recently associated with imbalance. With age, cells become senescent response stress wherein they undergo irreversible growth arrest while maintaining high metabolic activity. An accumulation linked various and chronic pathologies due overexpression senescence-associated secretory phenotype (SASP) comprised proinflammatory cytokines, chemokines, factors, proteases, lipids extracellular matrix components. In particular, dermatological disorders may promoted by as a common site accumulation. gut microbiota influences disruption gut-skin axis secretion metabolites. Metabolomics can used identify quantify metabolites involved senescence. Moreover, novel anti-senescent therapeutics are warranted given poor safety profiles current pharmaceutical drugs. Probiotics prebiotics effective alternatives, considering relationship between healthy aging. further research composition under status needed develop immunomodulatory therapies.

Language: Английский

Citations

84
EETs alleviate alveolar epithelial cell senescence by inhibiting endoplasmic reticulum stress through the Trim25/Keap1/Nrf2 axis DOI Creative Commons
Chen‐Yu Zhang, Wenjing Zhong,

Yu‐Biao Liu

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 63, P. 102765 - 102765

Published: May 28, 2023

Alveolar epithelial cell (AEC) senescence is a key driver of variety chronic lung diseases. It remains challenge how to alleviate AEC and mitigate disease progression. Our study identified critical role epoxyeicosatrienoic acids (EETs), downstream metabolites arachidonic acid (ARA) by cytochrome p450 (CYP), in alleviating senescence. In vitro, we found that 14,15-EET content was significantly decreased senescent AECs. Exogenous EETs supplementation, overexpression CYP2J2, or inhibition degrading enzyme soluble epoxide hydrolase (sEH) increase alleviated AECs' Mechanistically, promoted the expression Trim25 ubiquitinate degrade Keap1 Nrf2 enter nucleus exert an anti-oxidant effect, thereby inhibiting endoplasmic reticulum stress (ERS) Furthermore, D-galactose (D-gal)-induced premature aging mouse model, degradation Trifluoromethoxyphenyl propionylpiperidin urea (TPPU, inhibitor sEH) inhibited protein p16, p21, γH2AX. Meanwhile, TPPU reduced degree age-related pulmonary fibrosis mice. has confirmed are novel anti-senescence substances for AECs, providing new targets treatment

Language: Английский

Citations

39
Cellular senescence in skin‐related research: Targeted signaling pathways and naturally occurring therapeutic agents DOI Creative Commons
Aleksandra Dańczak‐Pazdrowska, Justyna Gornowicz‐Porowska, Adriana Polańska

et al.

Aging Cell, Journal Year: 2023, Volume and Issue: 22(6)

Published: April 11, 2023

Abstract Despite the growing interest by researchers into cellular senescence, a hallmark of aging, its role in human skin remains equivocal. The is largest and most accessible organ, reacting to external internal environment. Hence, it an organ choice investigate senescence target root‐cause aging processes using senolytic senomorphic agents, including naturally occurring plant‐based derivatives. This review presents different aspects from physiology pathology signaling pathways. Cellular can have both beneficial detrimental effects on skin, indicating that prosenescent antisenescent therapies may be desirable, based context. Knowledge molecular mechanisms involved provide meaningful insights for developing effective therapeutics senescence‐related disorders, such as wound healing cosmetic changes.

Language: Английский

Citations

34