Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Short senolytic or senostatic interventions rescue progression of radiation-induced frailty and premature ageing in mice Cancer survivors suffer from progressive frailty, multimorbidity and premature morbidity. We hypothesize that therapy-induced senescence and senescence progression via bystander effects is a significant cause of this premature ageing phenotype. Accordingly, the study addresses the question whether a short anti-senescence intervention is able to block progression of radiation-induced frailty and disability in a pre-clinical setting.

Male mice were sub-lethally irradiated at 5 months of age and treated (or not) with either a senolytic drug (Navitoclax or dasatinib + quercetin) for 10 days or with the senostatic metformin for 10 weeks. Follow up was for one year. Treatments commencing within a month after irradiation effectively reduced frailty progression (p<0.05) and improved muscle (p<0.01) and liver (p<0.05) function as well as short-term memory (p<0.05) until advanced age with no need for repeated interventions. Senolytic interventions that started late, after radiation-induced premature frailty was manifest, still had beneficial effects on frailty (p<0.05) and short-term memory (p<0.05). Metformin was similarly effective as senolytics. At therapeutically achievable concentrations metformin acted as a senostatic neither via inhibition of mitochondrial complex I, nor via improvement of mitophagy or mitochondrial function, but by reducing non-mitochondrial ROS production via NOX4 inhibition in senescent cells.

Our study suggests that the progression of adverse long-term health and quality-of-life effects of radiation exposure, as experienced by cancer survivors, might be rescued by short-term adjuvant anti-senescence interventions.
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The categories of this paper are: biochemistry
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The categories of this paper are: behavior
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The categories of this paper are: epidemiology
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The categories of this paper are: toxicology
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The categories of this paper are: neuroscience
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The categories of this paper are: genetics
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The categories of this paper are: communication
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The categories of this paper are: paleontology
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The categories of this paper are: microbiology
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The categories of this paper are: molecular
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The categories of this paper are: physiology
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The categories of this paper are: bioengineering
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The categories of this paper are: pathology
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The categories of this paper are: education
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The categories of this paper are: developmental
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The categories of this paper are: cell