Nature Aging, Год журнала: 2023, Номер 3(10), С. 1251 - 1268
Опубликована: Сен. 18, 2023
Язык: Английский
Cell, Год журнала: 2024, Номер 187(16), С. 4150 - 4175
Опубликована: Авг. 1, 2024
Cellular senescence is a cell fate triggered in response to stress and characterized by stable cell-cycle arrest hypersecretory state. It has diverse biological roles, ranging from tissue repair chronic disease. The development of new tools study vivo paved the way for uncovering its physiological pathological roles testing senescent cells as therapeutic target. However, lack specific broadly applicable markers makes it difficult identify characterize tissues living organisms. To address this, we provide practical guidelines called "minimum information cellular experimentation vivo" (MICSE). presents an overview rodent tissues, transgenic models, non-mammalian systems, human tumors their use identification specification cells. These uniform, state-of-the-art, accessible toolset improve our understanding vivo.
Язык: Английский
Процитировано
64
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
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Июнь 18, 2024
Abstract Tumorigenesis is a multistep process, with oncogenic mutations in normal cell conferring clonal advantage as the initial event. However, despite pervasive somatic and expansion tissues, their transformation into cancer remains rare event, indicating presence of additional driver events for progression to an irreversible, highly heterogeneous, invasive lesion. Recently, researchers are emphasizing mechanisms environmental tumor risk factors epigenetic alterations that profoundly influencing early malignant evolution, independently inducing mutations. Additionally, evolution tumorigenesis reflects multifaceted interplay between cell-intrinsic identities various cell-extrinsic exert selective pressures either restrain uncontrolled proliferation or allow specific clones progress tumors. by which induce both intrinsic cellular competency remodel stress facilitate not fully understood. In this review, we summarize genetic, epigenetic, external events, effects on co-evolution transformed cells ecosystem during initiation evolution. A deeper understanding earliest molecular holds promise translational applications, predicting individuals at high-risk developing strategies intercept transformation.
Язык: Английский
Процитировано
53
Molecular Cancer, Год журнала: 2024, Номер 23(1)
Опубликована: Май 18, 2024
Abstract Aging and cancer exhibit apparent links that we will examine in this review. The null hypothesis aging coincide because both are driven by time, irrespective of the precise causes, can be confronted with idea share common mechanistic grounds referred to as ‘hallmarks’. Indeed, several hallmarks also contribute carcinogenesis tumor progression, but some molecular cellular characteristics may reduce probability developing lethal cancer, perhaps explaining why very old age (> 90 years) is accompanied a reduced incidence neoplastic diseases. We discuss possibility process itself causes meaning time-dependent degradation supracellular functions accompanies produces byproduct or ‘age-associated disease’. Conversely, its treatment erode health drive process, has dramatically been documented for survivors diagnosed during childhood, adolescence, young adulthood. conclude connected superior including endogenous lifestyle factors, well bidirectional crosstalk, together render not only risk factor an important parameter must considered therapeutic decisions.
Язык: Английский
Процитировано
43
Immunity, Год журнала: 2024, Номер 57(3), С. 513 - 527.e6
Опубликована: Янв. 22, 2024
Язык: Английский
Процитировано
39
Science, Год журнала: 2024, Номер 386(6720)
Опубликована: Сен. 5, 2024
Age is a major risk factor for cancer, but how aging impacts tumor control remains unclear. In this study, we establish that of the immune system, regardless age stroma and tumor, drives lung cancer progression. Hematopoietic enhances emergency myelopoiesis, resulting in local accumulation myeloid progenitor–like cells tumors. These are source interleukin (IL)–1⍺, which enhanced response. The age-associated decline DNA methyltransferase 3A IL-1⍺ production, disrupting IL-1 receptor 1 signaling early during development normalized myelopoiesis slowed growth lung, colonic, pancreatic human tumors, identified an enrichment IL-1⍺–expressing monocyte-derived macrophages linked to age, poorer survival, recurrence, unraveling promotes offering actionable therapeutic strategies.
Язык: Английский
Процитировано
27
Molecular Cancer, Год журнала: 2024, Номер 23(1)
Опубликована: Авг. 31, 2024
Cellular senescence (CS), a permanent and irreversible arrest of the cell cycle proliferation leading to degeneration cellular structure function, has been implicated in various key physiological pathological processes, particularly cancer. Initially, CS was recognized as barrier tumorigenesis, serving an intrinsic defense mechanism protect cells from malignant transformation. However, increasing evidence suggests that senescent can promote tumor progression overt malignancy, primarily through set factors known senescence-associated secretory phenotypes (SASPs), including chemokines, growth factors, cytokines, stromal metalloproteinases. These significantly reshape microenvironment (TME), enabling tumors evade immune destruction. Interestingly, some studies have also suggested SASPs may impede development by enhancing immunosurveillance. opposing roles highlight complexity heterogeneity diverse cancers. Consequently, there growing interest pharmacological interventions targeting or cancer therapy, such senolytics senomorphics, either clearance mitigate harmful effects SASPs. In this review, we will interpret concept CS, delve into role reshaping TME, summarize recent advances anti-tumor strategies
Язык: Английский
Процитировано
26
Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 14(4), С. 1508 - 1524
Опубликована: Янв. 20, 2024
Macrophage senescence, manifested by the special form of durable cell cycle arrest and chronic low-grade inflammation like senescence-associated secretory phenotype, has long been considered harmful. Persistent senescence macrophages may lead to maladaptation, immune dysfunction, finally development age-related diseases, infections, autoimmune malignancies. However, it is a ubiquitous, multi-factorial, dynamic complex phenomenon that also plays roles in remodeled processes, including wound repair embryogenesis. In this review, we summarize some general molecular changes several specific biomarkers during macrophage which bring new sight recognize senescent different conditions. Also, take an in-depth look at functional macrophages, metabolism, autophagy, polarization, phagocytosis, antigen presentation, infiltration or recruitment. Furthermore, degenerations diseases associated with as well mechanisms relevant genetic regulations are integrated, not only emphasizing possibility regulating benefit age-associated but implication on finding potential targets drugs clinically.
Язык: Английский
Процитировано
21
Nature Cell Biology, Год журнала: 2024, Номер 26(8), С. 1336 - 1345
Опубликована: Авг. 1, 2024
The accumulation of senescent cells promotes ageing and age-related diseases, but molecular mechanisms that use to evade immune clearance accumulate in tissues remain be elucidated. Here we report p16-positive upregulate the checkpoint protein programmed death-ligand 1 (PD-L1) chronic inflammation. We show p16-mediated inhibition cell cycle kinases CDK4/6 induces PD-L1 stability via downregulation its ubiquitin-dependent degradation. p16-expressing alveolar macrophages elevate promote an immunosuppressive environment can contribute increased burden cells. Treatment with activating anti-PD-L1 antibodies engaging Fcγ receptors on effector leads elimination Our study uncovers a mechanism p16-dependent regulation reveals potential targeting improve immunosurveillance ameliorate senescence-associated
Язык: Английский
Процитировано
20
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(11), С. 6023 - 6023
Опубликована: Май 30, 2024
Royal jelly (RJ) is a highly nutritious natural product with great potential for use in medicine, cosmetics, and as health-promoting food. This bee mixture of important compounds, such proteins, vitamins, lipids, minerals, hormones, neurotransmitters, flavonoids, polyphenols, that underlie the remarkable biological therapeutic activities RJ. Various bioactive molecules like 10-hydroxy-2-decenoic acid (10-HDA), antibacterial protein, apisin, major royal specific peptides apisimin, royalisin, royalactin, apidaecin, defensin-1, jelleins are characteristic ingredients RJ shows numerous physiological pharmacological properties, including vasodilatory, hypotensive, antihypercholesterolaemic, antidiabetic, immunomodulatory, anti-inflammatory, antioxidant, anti-aging, neuroprotective, antimicrobial, estrogenic, anti-allergic, anti-osteoporotic, anti-tumor effects. Moreover, may reduce menopause symptoms improve health reproductive system, liver, kidneys, promote wound healing. article provides an overview molecular mechanisms underlying beneficial effects various diseases, aging, aging-related complications, special emphasis on components their properties. The data presented should be incentive future clinical studies hopefully will advance our knowledge about facilitate development novel RJ-based opportunities improving human well-being.
Язык: Английский
Процитировано
19