Characteristic Hallmarks of Aging and the Impact on Carcinogenesis

Abstract

Evidence shows that there is a synergistic, bidirectional association between cancer and aging with many shared traits. Age itself is a risk factor for the onset of most cancers while evidence suggests that cancer and its treatments might accelerate aging by causing genotoxic and cytotoxic insults. Aging has been associated with a series of alterations that can be linked to cancer: i) genomic instability caused by DNA damage or epigenetic alterations coupled with repair errors, which lead to progressive accumulation of mutations; ii) telomere attrition with possible impairment of telomerase, shelterin complex, or the trimeric complex (Cdc13, Stn1 and Ten1 – CST) activities associated with abnormalities in DNA replication and repair; iii) altered proteostasis especially when leading to an augmented proteasome, chaperon and autophagy-lysosome activity; iv) mitochondrial dysfunction causing oxidative stress; v) cellular senescence; vi) stem cells exhaustion, intercellular altered communication and deregulated nutrient sensing which are associated with microenvironmental modifications which may facilitate the subsequential role of cancer stem cells. Nowadays anti-growth factor agents and epigenetic therapies seem to assume an increasing role to fight aging-related diseases, especially cancer. This report aims to discuss the impact of age on cancer growth.

Conventional Radiological Profile of Metastatic Bone Disease Based on Its Histopathological Results: A 3-Year Experience

“…Increased incidence of MBD is proportionately similar to the incidence of cancer in general due to genome instability, telomere attrition, altered proteostasis, mitochondrial dysfunction, cellular senescence, and stem cell exhaustion, hence increasing genetic errors and mutation and subsequently increasing chances of cancer and metastasis. 13 However, there were some cases where MBD occurs in childhood and in this study, the youngest MBD patient was 5 years old with primary cancer from the kidney (Wilms tumor).…”

Melatonin, BAG-1 and cortisol circadian interactions in tumor pathogenesis and patterned immune responses

“…Aging is a major susceptibility factor for most medical conditions, including most human cancers [ 37 ]. The association of aging with the susceptibility to cancer and other medical conditions is classically linked to the raised levels of oxidative stress, leading to ROS-driven DNA damage and alterations in miRNAs that dysregulate patterned gene induction [ 38 ]. The raised levels of oxidative stress and inflammation over the course of aging that increase cancer risk are importantly determined by the dramatic, but gradual, ten-fold decrease in pineal gland melatonin production between childhood and the ninth decade of life [ 39 ].…”

“…Aging is a major susceptibility factor for most medical conditions, including most human cancers [37]. The association of aging with the susceptibility to cancer and other medical conditions is classically linked to the raised levels of oxidative stress, leading to ROS-driven DNA damage and alterations in miRNAs that dysregulate patterned gene induction [38].…”

The janus face of oxidative stress in health and disease: The cause or the cure?

“…According to Denham Harman's 1956 free radical theory of aging (FRTA), the loss of function that occurs in old age results from the cellular accumulation of free radicals (62). In addition to having confirmed this theory, more recent studies have highlighted that oxidative stress can also play a role in pathologies whose frequency increases with age, such as cancer, neurodegeneration, arthritis, atherosclerosis, and metabolic pathologies such as diabetes and obesity (63)(64)(65).…”