Hallmarks of aging: An expanding universe

Cell, Год журнала: 2023, Номер 186(2), С. 243 - 278

Опубликована: Янв. 1, 2023

Язык: Английский

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Telomere dysfunction in ageing and age-related diseases

Nature Cell Biology, Год журнала: 2022, Номер 24(2), С. 135 - 147

Опубликована: Фев. 1, 2022

Язык: Английский

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Strategies for targeting senescent cells in human disease

Nature Aging, Год журнала: 2021, Номер 1(10), С. 870 - 879

Опубликована: Окт. 7, 2021

Язык: Английский

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Targeting cellular senescence with senotherapeutics: senolytics and senomorphics

FEBS Journal, Год журнала: 2022, Номер 290(5), С. 1362 - 1383

Опубликована: Янв. 11, 2022

The concept of geroscience is that since ageing the greatest risk factor for many diseases and conditions, targeting process itself will have impact on human health. Of hallmarks ageing, cellular senescence has emerged as a druggable therapeutic target extending healthspan in model organisms. Cellular cell state irreversible proliferative arrest driven by different types stress, including oncogene‐induced stress. Many senescent cells (SnCs) develop senescent‐associated secretory phenotype (SASP) comprising pro‐inflammatory cytokines, chemokines, proteases, bioactive lipids, inhibitory molecules, extracellular vesicles, metabolites, lipids other factors, able to promote chronic inflammation tissue dysfunction. SnCs up‐regulate anti‐apoptotic pathways (SCAPs) prevent them from dying despite accumulation damage DNA organelles. These SCAPs altered represent targets development senotherapeutic drugs induce selective death SnCs, specifically termed senolytics or suppress markers senescence, particular SASP, senomorphics. Here, we review current senomorphics treatment age‐related disorders extension healthy longevity. In addition, challenges documenting senolytic senomorphic activity pre‐clinical models clinical application senotherapeutics be discussed.

Язык: Английский

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Senolytics reduce coronavirus-related mortality in old mice

Science, Год журнала: 2021, Номер 373(6552)

Опубликована: Июнь 8, 2021

The COVID-19 pandemic has revealed the pronounced vulnerability of elderly and chronically ill to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced morbidity mortality. Cellular senescence contributes inflammation, multiple chronic diseases, age-related dysfunction, but effects on responses viral infection are unclear. Here, we demonstrate that senescent cells (SnCs) become hyper-inflammatory in response pathogen-associated molecular patterns (PAMPs), including SARS-CoV-2 spike protein-1, increasing expression entry proteins reducing antiviral gene non-SnCs through a paracrine mechanism. Old mice acutely infected with pathogens included SARS-CoV-2-related mouse β-coronavirus experienced increased nearly 100% Targeting SnCs by using senolytic drugs before or after pathogen exposure significantly reduced mortality, cellular senescence, inflammatory markers antibodies. Thus, SnC burden diseased aged individuals should enhance resilience reduce mortality infection, SARS-CoV-2.

Язык: Английский

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Therapy-Induced Senescence: Opportunities to Improve Anticancer Therapy

JNCI Journal of the National Cancer Institute, Год журнала: 2021, Номер 113(10), С. 1285 - 1298

Опубликована: Март 31, 2021

Cellular senescence is an essential tumor suppressive mechanism that prevents the propagation of oncogenically activated, genetically unstable, and/or damaged cells. Induction cell also one underlying mechanisms by which cancer therapies exert antitumor activity. However, increasing body evidence from preclinical studies demonstrates radiation and chemotherapy cause accumulation senescent cells (SnCs) both in normal tissue. SnCs tumors can, paradoxically, promote relapse, metastasis, resistance to therapy, part, through expression senescence-associated secretory phenotype. In addition, tissue can contribute certain radiation- chemotherapy-induced side effects. Because its multiple roles, cellular could serve as important target fight against cancer. This commentary provides a summary discussion at National Cancer Institute Workshop on Radiation, Senescence, (August 10-11, 2020, Institute, Bethesda, MD) regarding current status research, heterogeneity therapy-induced senescence, senotherapeutics molecular biomarkers, concept "one-two punch" therapy (consisting therapeutics induce followed selective clearance SnCs), integration with personalized adaptive therapy. It identifies key knowledge gaps outlines future directions this emerging field improve treatment outcomes for patients.

Язык: Английский

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Cellular senescence: all roads lead to mitochondria

FEBS Journal, Год журнала: 2022, Номер 290(5), С. 1186 - 1202

Опубликована: Янв. 20, 2022

Senescence is a multi-functional cell fate, characterized by an irreversible cell-cycle arrest and pro-inflammatory phenotype, commonly known as the senescence-associated secretory phenotype (SASP). Emerging evidence indicates that accumulation of senescent cells in multiple tissues drives tissue dysfunction several age-related conditions. This has spurred academic community industry to identify new therapeutic interventions targeting this process. Mitochondrial often-unappreciated hallmark cellular senescence which plays important roles not only growth but also development SASP resistance cell-death. Here, we review supports role for mitochondria describe underlying mechanisms. Finally, propose detailed road map mitochondrial biology will be crucial guide future senotherapies.

Язык: Английский

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The role of cellular senescence in cardiac disease: basic biology and clinical relevance

Nature Reviews Cardiology, Год журнала: 2021, Номер 19(4), С. 250 - 264

Опубликована: Окт. 19, 2021

Язык: Английский

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Skeletal Aging and Osteoporosis: Mechanisms and Therapeutics

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(7), С. 3553 - 3553

Опубликована: Март 29, 2021

Bone is a dynamic organ maintained by tightly regulated mechanisms. With old age, bone homeostasis, which an intricate balance between formation and resorption, undergoes deregulation. Oxidative stress-induced DNA damage, cellular apoptosis, senescence are all responsible for this tissue dysfunction the imbalance in homeostasis. These mechanisms have become target therapeutics to treat age-related osteoporosis. Genetic mouse models shown importance of senescent cell clearance alleviating Furthermore, we others that targeting pharmacologically was effective tool alleviate age- radiation-induced Senescent cells also altered secretome known as associated secretory phenotype (SASP), may autocrine, paracrine, or endocrine function. The current review discusses potential pathways lead profile aged skeleton how homeostasis affected during has discussed existing treatment osteoporosis rationalizes novel therapeutic options based on SASP underlying pathogenesis aging bone.

Язык: Английский

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ROS: Basic Concepts, Sources, Cellular Signaling, and its Implications in Aging Pathways

Oxidative Medicine and Cellular Longevity, Год журнала: 2022, Номер 2022, С. 1 - 23

Опубликована: Окт. 19, 2022

Reactive oxygen species (ROS) are bioproducts of cellular metabolism. There is a range molecules with oxidizing properties known as ROS. Despite those being implied negatively in aging and numerous diseases, their key role signaling evident. ROS control several biological processes such inflammation, proliferation, cell death. The redox underlying these events one characteristic the new generation scientists aimed at defining environment. potential, which includes balance sources antioxidant system, implies an important target for understanding cells’ fate derived from signaling. In this review, we summarized chemical, balance, signaling, implications aging.

Язык: Английский

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