The impact of radiotherapy on cellular senescence and chronic inflammation

Abstract

Background: Ageing is a process leading to a gradual loss of function on cell, tissue and organ level. Age-related processes can be accelerated by a wide range of extrinsic and intrinsic stimuli. Cancer-directed therapies, including radiation therapy, can lead to the activation of chronic inflammatory processes, leading to the shrinkage of physiologic reserve, and therefore to the premature onset of age-related signs and symptoms. The assessment of the manifestations of ageing process can be conducted by the measurement of biomarkers of ageing in the blood, evaluations of the health status with the tools of comprehensive geriatric assessment as well as with the estimation of cellular senescence by the means of measurement of the telomere erosion on the chromosomes. Since the considerable percentage of cancer patients are elderly individuals, the investigation of the influence of cancer therapy on the ageing process gains more and more attention in science. Methods: A total of 314 patients treated with definitive radiation therapy (RT) for prostate cancer at the Department of Therapeutic Radiology and Oncology, Medical University of Graz were enrolled into our observational prospective study and underwent a comprehensive health status evaluation with the tools of geriatric assessment (GA) as well as the assessment of inflammatory parameters and measurement of leucocyte telomere length prior to the start of treatment and at two follow-ups 3 and 15 months after the completion of radiation. Blood sampling and measurement of biomarkers of ageing was also conducted at the end of RT course. The alterations of clinical, biochemical and molecular domains of ageing were evaluated with non-parametric tests. Additionally, correlations between pretherapeutic GA results and ageing-related biomarkers were analysed. Results: During the observation time, a significant decline was observed in patients’ social situation (p0.05). Furthermore, we could observe an improvement in cognitive function (p=0.004) and patients’ mobility (p=0.032) between the pretherapeutic status and one of the reassessments. The results of biochemical markers of ageing showed a significant increase of fibrinogen (p

Datum der Bewilligung	2024
Originalsprache	Englisch
Gradverleihende Hochschule	Medizinische Universität Graz
Betreuer/-in	Tanja Langsenlehner (Betreuer*in) & Wilfried Renner (Betreuer*in)