Cellular senescence in brain aging and cognitive decline DOI Creative Commons
Areez Shafqat, Saifullah Khan, Mohamed H. Omer

и другие.

Frontiers in Aging Neuroscience, Год журнала: 2023, Номер 15

Опубликована: Ноя. 23, 2023

Cellular senescence is a biological aging hallmark that plays key role in the development of neurodegenerative diseases. Clinical trials are currently underway to evaluate effectiveness senotherapies for these However, impact on brain and cognitive decline absence neurodegeneration remains uncertain. Moreover, patient populations like cancer survivors, traumatic injury obese individuals, obstructive sleep apnea patients, chronic kidney disease patients can suffer age-related changes prematurely, suggesting they may accelerated brain. Understanding neurocognitive deficits linked conditions crucial, especially considering rapidly evolving field senotherapeutics. Such treatments could help alleviate early significantly reducing morbidity healthcare costs. This review provides translational perspective how cellular decline. We also discuss important caveats surrounding mainstream senolytics senomorphics, present emerging evidence hyperbaric oxygen therapy immune-directed therapies as viable modalities senescent cell burden.

Язык: Английский

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

Louise E. Pitcher,

Matthew J. Yousefzadeh

и другие.

Journal of Clinical Investigation, Год журнала: 2022, Номер 132(15)

Опубликована: Июль 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.

Язык: Английский

Процитировано

309
Advances in PET imaging of cancer DOI
Johannes Schwenck, Dominik Sonanini, Jonathan Cotton

и другие.

Nature reviews. Cancer, Год журнала: 2023, Номер 23(7), С. 474 - 490

Опубликована: Май 31, 2023

Язык: Английский

Процитировано

102
Aging of mesenchymal stem cell: machinery, markers, and strategies of fighting DOI Creative Commons
Mahmoud Al‐Azab,

Mohammed Safi,

Elina Idiiatullina

и другие.

Cellular & Molecular Biology Letters, Год журнала: 2022, Номер 27(1)

Опубликована: Авг. 19, 2022

Human mesenchymal stem cells (MSCs) are primary multipotent capable of differentiating into osteocytes, chondrocytes, and adipocytes when stimulated under appropriate conditions. The role MSCs in tissue homeostasis, aging-related diseases, cellular therapy is clinically suggested. As aging a universal problem that has large socioeconomic effects, an improved understanding the concepts can direct public policies reduce its adverse impacts on healthcare system humanity. Several studies have been carried out over several years to understand phenomenon different factors affecting human aging. A reduced ability adult cell populations reproduce regenerate one main contributors process. In this context, senescence major challenge front advancement. Many factors, ranging from genetic metabolic pathways extrinsic through various signaling pathways, involved regulating mechanism MSC senescence. To better reverse senescence, review highlights underlying mechanisms signs discusses strategies combat

Язык: Английский

Процитировано

90
Cellular Senescence and Ageing: Mechanisms and Interventions DOI Creative Commons

Andreas Mylonas,

Ana O’Loghlen

Frontiers in Aging, Год журнала: 2022, Номер 3

Опубликована: Март 29, 2022

The influence of the activation a cellular phenotype termed senescence and it’s importance in ageing age-related diseases is becoming more evident. In fact, there huge effort to tackle these via therapeutic drugs targeting senescent cells named senolytics. However, clearer understanding how activated it has on specific types tissues needed. Here, we describe general triggers characteristics senescence. addition, different diseases.

Язык: Английский

Процитировано

77
Rutin is a potent senomorphic agent to target senescent cells and can improve chemotherapeutic efficacy DOI Creative Commons
Hanxin Liu,

Qixia Xu,

Halidan Wufuer

и другие.

Aging Cell, Год журнала: 2023, Номер 23(1)

Опубликована: Июль 20, 2023

Abstract Aging is a major risk factor for most chronic disorders, which cellular senescence one of the central hallmarks. Senescent cells develop pro‐inflammatory senescence‐associated secretory phenotype (SASP), significantly contributes to organismal aging and age‐related disorders. Development senotherapeutics, an emerging class therapeutic agents target senescent cells, allows effectively delay alleviate pathologies. Here we report preliminary outputs from screening natural medicinal agent (NMA) library senotherapeutic candidates validated several with prominent potential as senomorphics. Rutin, phytochemical constituent found in number plants, showed remarkable capacity targeting by dampening expression full spectrum SASP. Further analysis indicated that rutin restrains acute stress‐associated (ASAP) specifically interfering interactions ATM HIF1α, master regulator systemic homeostasis activated during senescence, TRAF6, part key signaling axis supporting ASAP development toward Conditioned media produced stromal enhanced malignant phenotypes prostate cancer including vitro proliferation, migration, invasion, more importantly, chemoresistance, while remarkably downregulated these gain‐of‐functions. Although classic chemotherapy reduced tumor progression, treatment outcome was substantially improved upon combination chemotherapeutic rutin. Our study provides proof concept senomorphic agent, presents effective avenue alleviating pathologies cancer.

Язык: Английский

Процитировано

69
Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction DOI Creative Commons
Corina Amor, Inés Fernández-Maestre,

Saria Chowdhury

и другие.

Nature Aging, Год журнала: 2024, Номер 4(3), С. 336 - 349

Опубликована: Янв. 24, 2024

Senescent cells, which accumulate in organisms over time, contribute to age-related tissue decline. Genetic ablation of senescent cells can ameliorate various pathologies, including metabolic dysfunction and decreased physical fitness. While small-molecule drugs that eliminate ('senolytics') partially replicate these phenotypes, they require continuous administration. We have developed a senolytic therapy based on chimeric antigen receptor (CAR) T targeting the senescence-associated protein urokinase plasminogen activator (uPAR), we previously showed safely young animals. now show uPAR-positive during aging be targeted with CAR cells. Treatment anti-uPAR improves exercise capacity physiological aging, it ameliorates (for example, improving glucose tolerance) aged mice high-fat diet. Importantly, single administration is sufficient achieve long-term therapeutic preventive effects.

Язык: Английский

Процитировано

61
A review of the pathophysiological mechanisms of doxorubicin-induced cardiotoxicity and aging DOI Creative Commons
Annet N. Linders, Itamar Braga Dias, Teresa López‐Fernández

и другие.

npj Aging, Год журнала: 2024, Номер 10(1)

Опубликована: Янв. 23, 2024

Abstract The population of cancer survivors is rapidly increasing due to improving healthcare. However, therapies often have long-term side effects. One example therapy-related cardiac dysfunction (CTRCD) caused by doxorubicin: up 9% the patients treated with this drug develop heart failure at a later stage. In recent years, doxorubicin-induced cardiotoxicity has been associated an accelerated aging phenotype and cellular senescence in heart. review we explain evidence doxorubicin-treated comparing it healthy aged hearts, shed light on treatment strategies that are proposed pre-clinical settings. We will discuss impact could clinic future research.

Язык: Английский

Процитировано

52
Obesity-related kidney disease: Beyond hypertension and insulin-resistance DOI Creative Commons
Tarek Ziad Arabi, Areez Shafqat, Belal Nedal Sabbah

и другие.

Frontiers in Endocrinology, Год журнала: 2023, Номер 13

Опубликована: Янв. 16, 2023

Chronic kidney disease (CKD) causes considerable morbidity, mortality, and health expenditures worldwide. Obesity is a significant risk factor for CKD development, partially explained by the high prevalence of diabetes mellitus hypertension in obese patients. However, adipocytes also possess potent endocrine functions, secreting myriad cytokines adipokines that contribute to insulin resistance induce chronic low-grade inflammatory state thereby damaging kidney. development itself associated with various metabolic alterations exacerbate adipose tissue dysfunction resistance. This adipose-renal axis major focus current research, given rising incidence obesity. Cellular senescence biologic hallmark aging, age another obesity CKD. An elevated senescent cell burden predicts renal animal models, senotherapies may alleviate these phenotypes. In this review, we discuss direct mechanisms which contributes emphasizing potential clinical importance such pathways augmenting care

Язык: Английский

Процитировано

46
Reshaping of the tumor microenvironment by cellular senescence: An opportunity for senotherapies DOI Creative Commons

Mariantonietta D’Ambrosio,

Jesús Gil

Developmental Cell, Год журнала: 2023, Номер 58(12), С. 1007 - 1021

Опубликована: Июнь 1, 2023

Язык: Английский

Процитировано

41
Cellular senescence in lung cancer: Molecular mechanisms and therapeutic interventions DOI Creative Commons
Saurav Kumar Jha, Gabriele De Rubis, Shankar Raj Devkota

и другие.

Ageing Research Reviews, Год журнала: 2024, Номер 97, С. 102315 - 102315

Опубликована: Апрель 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.

Язык: Английский

Процитировано

26