Cellular senescence and senolytics: the path to the clinic

Nature Medicine, Год журнала: 2022, Номер 28(8), С. 1556 - 1568

Опубликована: Авг. 1, 2022

Язык: Английский

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Multimorbidity

Nature Reviews Disease Primers, Год журнала: 2022, Номер 8(1)

Опубликована: Июль 14, 2022

Язык: Английский

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A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Авг. 16, 2022

Although cellular senescence drives multiple age-related co-morbidities through the senescence-associated secretory phenotype, in vivo senescent cell identification remains challenging. Here, we generate a gene set (SenMayo) and validate its enrichment bone biopsies from two aged human cohorts. We further demonstrate reductions SenMayo following genetic clearance of cells mice adipose tissue humans pharmacological clearance. next use to identify hematopoietic or mesenchymal at single level murine marrow/bone scRNA-seq data. Thus, identifies across tissues species with high fidelity. Using this panel, are able characterize key intercellular signaling pathways. also represents potentially clinically applicable panel for monitoring burden aging other conditions as well studies senolytic drugs.

Язык: Английский

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Hallmarks of Health

Cell, Год журнала: 2020, Номер 184(1), С. 33 - 63

Опубликована: Дек. 18, 2020

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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Sex differences in biological aging with a focus on human studies

eLife, Год журнала: 2021, Номер 10

Опубликована: Май 13, 2021

Aging is a complex biological process characterized by hallmark features accumulating over the life course, shaping individual's aging trajectory and subsequent disease risks. There substantial individual variability in between men women. In general, women live longer than men, consistent with lower ages as assessed molecular biomarkers, but there paradox. Women are frailer have worse health at end of life, while still perform better physical function examinations. Moreover, many age-related diseases show sex-specific patterns. this review, we aim to summarize current knowledge on sexual dimorphism human studies, support from animal research, illnesses. We also attempt place it context theories aging, well discuss explanations for sex differences, example, sex-chromosome linked mechanisms hormonally driven differences.

Язык: Английский

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Advances in pathogenesis and therapeutic strategies for osteoporosis

Pharmacology & Therapeutics, Год журнала: 2022, Номер 237, С. 108168 - 108168

Опубликована: Март 10, 2022

Язык: Английский

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Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: the regulation and intervention

Signal Transduction and Targeted Therapy, Год журнала: 2021, Номер 6(1)

Опубликована: Июнь 28, 2021

Remarkable progress in ageing research has been achieved over the past decades. General perceptions and experimental evidence pinpoint that decline of physical function often initiates by cell senescence organ ageing. Epigenetic dynamics immunometabolic reprogramming link to alterations cellular response intrinsic extrinsic stimuli, representing current hotspots as they not only (re-)shape individual identity, but also involve fate decision. This review focuses on present findings emerging concepts epigenetic, inflammatory, metabolic regulations consequences process. Potential therapeutic interventions targeting regulatory mechanisms, using state-of-the-art techniques are discussed.

Язык: Английский

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The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice

Nature Metabolism, Год журнала: 2021, Номер 3(12), С. 1706 - 1726

Опубликована: Дек. 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.

Язык: Английский

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Osteoporosis: Pathophysiology and therapeutic options.

PubMed, Год журнала: 2020, Номер 19, С. 1017 - 1037

Опубликована: Янв. 1, 2020

Osteoporosis is a metabolic bone disease that, on cellular level, results from osteoclastic resorption not compensated by osteoblastic formation. This causes bones to become weak and fragile, thus increasing the risk of fractures. Traditional pathophysiological concepts osteoporosis focused endocrine mechanisms such as estrogen or vitamin D deficiency well secondary hyperparathyroidism. However, research over last decades provided exiting new insights into contributing onset osteoporosis, which go far beyond this. Selected interactions between immune system, gut microbiome, senescence are reviewed in this article. Furthermore, an overview currently available medications including antiresorptive forming drugs outlook potential future treatment options given.

Язык: Английский

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