Older organs provide a substantial unrealized potential with the capacity to close the gap between demand and supply in organ transplantation. The potential of senolytics in improving age-related conditions has been shown in various experimental studies and early clinical trials. Those encouraging data may also be of relevance for transplantation. As age-differences between donor and recipients are not uncommon, aging may be accelerated in recipients when transplanting older organs; young organs may, at least in theory, have the potential to 'rejuvenate' old recipients. Here, we review the relevance of senescent cells and the effects of senolytics on organ quality, alloimmune responses and outcomes in solid organ transplantation. This article is part of the Special Issue - Senolytics - Edited by Joao Passos and Diana Jurk.
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http://dx.doi.org/10.1016/j.mad.2021.111582 | DOI Listing |
Inflammaging refers to chronic, low-grade inflammation that becomes more common with age and plays a central role in the pathophysiology of various vascular diseases. Key inflammatory mediators involved in inflammaging contribute to endothelial dysfunction and accelerate the progression of atherosclerosis. In addition, specific pathological mechanisms and the role of inflammasomes have emerged as critical drivers of immune responses within the vasculature.
View Article and Find Full Text PDFJ Dent Res
January 2025
Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Cellular senescence has emerged as one of the central hallmarks of aging and drivers of chronic comorbidities, including periodontal diseases. Senescence can also occur in younger tissues and instigate metabolic alterations and dysfunction, culminating in accelerated aging and pathological consequences. Senotherapeutics, such as the combination of dasatinib and quercetin (DQ), are being increasingly used to improve the clinical outcomes of chronic disorders and promote a healthy life span through the reduction of senescent cell burden and senescence-associated secretory phenotype (SASP).
View Article and Find Full Text PDFNat Aging
January 2025
National Clinical Research Center for Aging and Medicine, Huashan Hospital and MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Gut microbiota plays a crucial role in the host health in the aging process. However, the mechanisms for how gut microbiota triggers cellular senescence and the consequent impact on human aging remain enigmatic. Here we show that phenylacetylglutamine (PAGln), a metabolite linked to gut microbiota, drives host cellular senescence.
View Article and Find Full Text PDFAging (Albany NY)
January 2025
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
Exposure to ionizing radiation (IR), both low-LET (e.g., X-rays, γ rays) and high-LET (e.
View Article and Find Full Text PDFBiomacromolecules
January 2025
Macromolecular Engineering Laboratory, Institute of Energy and Process Engineering, Department of Mechanical and Process Engineering, ETH Zurich, 8092 Zurich, Switzerland.
Small molecules are frontline therapeutics for many diseases; however, they are often limited by their poor solubility. Therefore, hydrophobic small molecules are often encapsulated or prepared as pure drug nanoparticles. Navitoclax, used to eliminate senescent cells, is one such small molecule that faces challenges in translation due to its hydrophobicity and toxic side effects.
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