Background: Senescence is a cellular ageing process in all multicellular organisms. It is characterized by a decline in cellular functions and proliferation, resulting in increased cellular damage and death. This condition plays an essential role in the ageing process and significantly contributes to the development of age-related complications. On the other hand, ferroptosis is a systemic cell death 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 illnesses, including cardiovascular disease, neurodegeneration, and cancer. Relevance of these conditions to ageing and disease: Senescence is believed to contribute to the decline in tissue and organ function that occurs with ageing. 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. On the other hand, ferroptosis has been linked to the development of various health disorders, including neurodegeneration, cardiovascular disease, and cancer [1]. It is known to play a role in developing these diseases by promoting the death of damaged or diseased cells and contributing to the inflammation often associated with them. Both senescence and ferroptosis are complex processes that are still not fully understood. Further research is needed to thoroughly understand the role of these processes in ageing and disease, and to identify potential interventions to target these processes to prevent or treat age-related conditions. Objectives: This systematic review aims to assess the potential mechanisms underlying the link connecting senescence, ferroptosis, ageing, and disease.

The spike protein (S) of SARS-CoV-2 has been shown to bind to the human angiotensin-converting enzyme 2 (ACE2) receptor with much higher affinity compared to other coronaviruses. The binding interface between the ACE2 receptor plays a critical role in the entry mechanism of SARS-CoV-2 virus. There are specific amino acids involved in the interaction between S protein and ACE2 receptor. This specificity is critical for the virus to establish a systemic infection and cause COVID-19 disease. In the ACE2 receptor, the largest number of amino acids that play a crucial role in the mechanism of interaction and recognition with the S protein are located in the C-terminal part which represents the main binding region between ACE2 and S. This fragment is abundant in coordination residues such as aspartates, glutamates and histidine that could be targeted by metal ions. Zn²⁺ ion binds to the ACE2 receptor in its catalytic site and modulates its activity, but it could also contribute to the structural stability of the entire protein. The ability of the human ACE2 receptor to coordinate metal ions, such Zn²⁺, in the same region where it binds to the S protein could have a crucial impact in the mechanism of recognition and interaction of ACE2-S with consequences on their binding affinity that deserve to be investigated. To test this possibility, this study aims to characterize the coordination ability of Zn²⁺, and also Cu²⁺ for comparison, with selected peptide models of the ACE2 binding interface using spectroscopic and potentiometric techniques.