Cellular Senescence: A Translational Perspective
By J. Kirkland, T. Tchkonia. EBioMedicine, 2017
902 citations recorded by the source corpus.
Cellular senescence entails essentially irreversible replicative arrest, apoptosis resistance, and frequently acquisition of a pro-inflammatory, tissue-destructive senescence-associated secretory phenotype (SASP). Senescent cells accumulate in various tissues with aging and at sites of pathogenesis in many chronic diseases and conditions. The SASP can contribute to senescence-related inflammation, metabolic dysregulation, stem cell dysfunction, aging phenotypes, chronic diseases, geriatric syndromes, and loss of resilience. Delaying senescent cell accumulation or reducing senescent cell burden is associated with delay, prevention, or alleviation of multiple senescence-associated conditions. We used a hypothesis-driven approach to discover pro-survival Senescent Cell Anti-apoptotic Pathways (SCAPs) and, based on these SCAPs, the first senolytic agents, drugs that cause senescent cells to become susceptible to their own pro-apoptotic microenvironment. Several senolytic agents, which appear to alleviate multiple senescence-related phenotypes in pre-clinical models, are beginning the process of being translated into clinical interventions that could be transformative.
Subfields: Aging, Immunology, Physiology
View Paper: https://www.semanticscholar.org/paper/2deb602e3fe7ded366c586da7599d324738e6367
How researchers see this paper
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In Aging
In Immunology
In Physiology
- J. Kirkland
- T. Tchkonia
- Nathan K. LeBrasseur
- T. Pirtskhalava
- Yi Zhu
- S. Khosla
- J. Passos
- Luigi Ferrucci
Citations in the corpus
- Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease (2019, background): “Insults such as serial passaging, DNA damage, exposure to the damage-associated molecular pattern molecules that accumulate in injured or chronically-diseased tissues, and metabolic insults can cause cells to become senescent [2].”
- Measuring biological aging in humans: A quest (2019, background): “Notably, senescent cells become resistant to apoptosis and may persist in tissues for many years unless they are removed by the immune system, therefore interfering with tissue repair and regeneration (Kirkland & Tchkonia, 2017).”
- Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study (2019, methodology): “If fisetin proves to be safe and effective in mouse IPF models, it would be a strong candidate to advance into clinical trials, as may be other next-generation senolytics [8,42].”