Non-Genomic Hallmarks of Aging-The Review.

Aging is a natural, gradual, and inevitable process associated with a series of changes at the molecular, cellular, and tissue levels that can lead to an increased risk of many diseases, including cancer. The most significant changes at the genomic level (DNA damage, telomere shortening, epigenetic changes) and non-genomic changes are referred to as hallmarks of aging. The hallmarks of aging and cancer are intertwined. Many studies have focused on genomic hallmarks, but non-genomic hallmarks are also important and may additionally cause genomic damage and increase the expression of genomic hallmarks. Understanding the non-genomic hallmarks of aging and cancer, and how they are intertwined, may lead to the development of approaches that could influence these hallmarks and thus function not only to slow aging but also to prevent cancer. In this review, we focus on non-genomic changes. We discuss cell senescence, disruption of proteostasis, deregualation of nutrient sensing, dysregulation of immune system function, intercellular communication, mitochondrial dysfunction, stem cell exhaustion and dysbiosis.

Biomarkers of aging - current state of knowledge.

Aging is a process of gradual decline in the functional capacity of the human body that leads to a significant increase in the risk of death over time. Although it is a process universal to all animals, its rate is not the same. Biomarkers of aging aim to better describe the aging process at the level of the individual, organ, tissue, or single cell. They are used to estimate the rate of aging and predict the probability of death. They are good indication of the current state of the organism and are more accurate in predicting a person's susceptibility to disease, its progression and the likelihood of complications and death. Simple biomarkers measure only one parameter or a narrow group of related parameters that have a known association with age, in human or in a laboratory model. They can be divided into molecular (based on features of aging), functional (describing decreasing functional capacity during aging) and anthropometric (describing structural changes). Composite biomarkers are the most comprehensive way of measuring biological age. They combine a large amount of data, which they evaluate using algorithms often based on artificial intelligence. The most widely used method for measuring biological age in composite biomarkers is the epigenetic clock. The aim of this article is to review the many existing markers of aging and describe their relationship to aging.

Physiology of ageing.

Aging is a process of gradually reducing abilities and functional capacities of the organism. It is a universal process with a considerable degree of variability that is characteristic of all higher animals. Among the theories of ageing, the theory of damage accumulation, which integrates the mechanisms of ageing known to date, is currently widely accepted. This theory is based on pathophysiological processes, injurious changes can occur in the human body. These changes can be understood as damage. Due to the continuous accumulation of damage, the whole system is subsequently deteriorated. The aim of the present work is to characterize the basic pathophysiological mechanisms of aging (damage) in the light of current scientific knowledge and to show them in their hierarchical context.

High-dose-rate brachytherapy at 3 Gy per fraction for lip carcinoma: Treatment outcomes and toxicity at 5-years.

PURPOSE: Low-dose-rate brachytherapy (LDR-BT) is a well-established treatment for lip cancer. High-dose-rate (HDR)-BT is a promising alternative to LDR-BT, but data are limited. In this context, we retrospectively evaluated treatment outcomes in a series of patients who underwent HDR-BT for lip carcinoma between 2003 and 2021. MATERIALS AND METHODS: A total of 32 patients were included in this study, with a median age of 73.5 years (range, 61 - 88). The indications for HDR-BT were as follows: primary treatment (n = 17), adjuvant treatment (n = 3), and recurrent disease after surgery (n = 12). The prescribed dose was 18 fractions of 3 Gy administered twice daily. RESULTS: At a median followup of 45 months (range, 12 -232), the 5-year local recurrence-free interval was 96.9% (95% CI: 90.9-100%), the disease-free interval was 85% (95% CI: 70.9-99.1), and 5-year overall survival was 64.7% (95% CI: 44.7-84.8). Eleven patients died, all on age related comorbidities. Acute toxicity manifested as G1 dry desquamation in 6 patients (18.8%), G2 erythema in 10 patients (31.2%) and G3 confluent moist desquamation in 16 patients (50%). Late complications included G1 fibrosis (100% of cases). G1 and G2 depigmentation was observed in 8 (25%) and 6 (18%) patients, G1 telangiectasia occurred in 5 patients (16%). CONCLUSIONS: These data support the use of HDR-BT for lip cancer. The dose and fractionation schedule used in this study (18 fractions x 3 Gy twice daily) seems to be effective and safe.

Combined Therapy of Locally Advanced Oesophageal and Gastro-Oesophageal Junction Adenocarcinomas: State of the Art and Aspects of Predictive Factors.

The following main treatment approaches are currently used in locally advanced adenocarcinomas of the oesophagus and gastrooesophageal junction (GOJ): preoperative chemoradiotherapy and surgery, and perioperative chemotherapy and surgery. While preoperative chemoradiotherapy is used primarily in oesophageal tumours, perioperative chemotherapy is the treatment of choice in Western countries for gastric cancer. The optimal treatment strategy for GOJ adenocarcinoma is still not clear. In comparison to other malignancies, biomarkers are used as predictive factors in distal oesophageal and GOJ adenocarcinomas in a very limited way, and moreover, only in metastatic stages (e.g., HER2 status, or microsatellite instability status). The aim of the article is to provide an overview of current treatment options in locally advanced adenocarcinomas of oesophagus and GOJ based on the latest evidence, including the possible potential of predictive biomarkers in optimizing treatment.