Potential connections between senescence and chemobrain: An early overview of literature

Abstract

Chemotherapy-induced cognitive impairment (CICI), commonly referred to as chemobrain, is a pervasive adverse effect of cancer treatment, characterized by deficits in memory, concentration, and executive function. Several observations have suggested a potential for senescence in mediating CICI. First, chemotherapeutic agents that are implicated in CICI can also trigger senescence in neurons and glial cells, accompanied by the senescence-associated secretory phenotype (SASP), that could propagate neuroinflammation, oxidative stress, and synaptic dysfunction. Second, the hippocampus, central to memory and learning, is particularly vulnerable to chemotherapy-induced dendritic spine loss, reduced neurogenesis, and mitochondrial damage and is also a site for senescent cell accumulation. Third, the role of senescence in CICI is further supported by recent studies showing that the selective elimination of senescent cells can mitigate features of CICI. In this work, we attempt to highlight the intricate interplay between the established mechanisms of CICI (oxidative stress, inflammation, DNA damage, and mitochondrial dysfunction) and explore their potential connection to senescence as a central mechanism contributing to CICI. If senescence is then proven to be an established mechanism of CICI, then the use of senolytics or senomorphics could represent novel pharmacological interventions for the treatment of chemobrain.