Ferroptosis and Senescence: A Systematic Review

Abstract

Senescence is a cellular aging process in all multicellular organisms. It is characterized by a decay in cellular functions and proliferation, resulting in increased cellular damage and death. This condition plays an essential role in the aging process and significantly contributes to the development of age-related complications. On the other hand, ferroptosis is a systemic cell death pathway characterized by excessive iron accumulation followed by the generation of reactive oxygen species (ROS). Oxidative stress is a common trigger of this condition and may be induced by various factors such as toxins, drugs, and inflammation. Ferroptosis is linked to numerous disorders, including cardiovascular disease, neurodegeneration, and cancer. Senescence is believed to contribute to the decay in tissue and organ functions occurring with aging. It has also been linked to the development of age-related pathologies, such as cardiovascular diseases, diabetes, and cancer. In particular, senescent cells have been shown to produce inflammatory cytokines and other pro-inflammatory molecules that can contribute to these conditions. In turn, ferroptosis has been linked to the development of various health disorders, including neurodegeneration, cardiovascular disease, and cancer. Ferroptosis is known to play a role in the development of these pathologies by promoting the death of damaged or diseased cells and contributing to the inflammation often associated. Both senescence and ferroptosis are complex pathways that are still not fully understood. Further research is needed to thoroughly investigate the role of these processes in aging and disease, and to identify potential interventions to target such processes in order to prevent or treat age-related conditions. This systematic review aims to assess the potential mechanisms underlying the link connecting senescence, ferroptosis, aging, and disease, and whether they can be exploited to block or limit the decay of the physiological functions in elderly people for a healthy longevity.

Escape from senescence: molecular basis and therapeutic ramifications

“…Unveiling the mechanistic insights governing this phenomenon is anticipated to boost and expand the therapeutic potential of senolysis and lead to the discovery of more effective tools in the arsenal against cancer. To that end, additional approaches could be tested, based on reagents that induce ferroptosis, a common type of death in senescent cells [148]. Overall, increasing our knowledge of the escape-from-senescence phenomenon carries significant translational potential to redirect currently applied therapies and to develop revolutionary treatments, improving clinical outcomes for cancer patients [138].…”

Antioxidant Systems as Modulators of Ferroptosis: Focus on Transcription Factors

“…In about ten years of research investigations, ferroptosis emerged as a type of cell death with a pivotal role in preventing or even facilitating the progression of many diseases (reviewed in [ 1 , 2 , 3 ]). In particular, ferroptosis is now considered a good therapeutic option to treat multiple forms of cancer and arrest tumor growth [ 3 , 4 , 5 ], as well as a causal factor in neurodegenerative disorders [ 6 ], senescence/aging [ 7 ], different blood diseases [ 8 ], and kidney- and ischemia-reperfusion injuries [ 9 , 10 ].…”

Ferroptosis and the ubiquitin-proteasome system: exploring treatment targets in cancer

“…The primary goal of cancer treatment research has been to eliminate malignant cells while protecting healthy cells ( Cassetta and Pollard, 2023 ). To prevent the uncontrolled growth of cancer cells and other abnormal tissues, the body relies on a process known as “regulated cell death” (RCD) to keep things in check ( Coradduzza et al, 2023 ; Huang et al, 2023 ). Apoptosis, paraptosis, necroptosis, and ferroptosis are among the distinct modes of RCD that have been characterized so far ( Tong et al, 2022 ).…”