Host-Pathogen Interaction as a Driver of Cellular Senescence: Microbial Triggers and Host Response

Despite extensive research, the complex relationship between cellular senescence, aging, and host–pathogen interactions remains incompletely understood. This paper aims to review cellular and molecular alterations of senescent cells and critically examine the role of bacterial infections as key drivers in immunosenescence. Molecular mechanisms underlying pathogen-induced stress responses and the subsequent impact on host tissues and immune function are also highlighted. The novelty of this work lies in integrating current knowledge into direct and indirect mechanisms by which bacterial pathogens induce senescence, including genotoxic effects, oxidative stress, and disruption of host signaling pathways. Particular emphasis is placed on how bacterial virulence factors modulate critical pathways such as p53–p21, p16INK4a–Rb, NF-κB, mTOR, and cGAS–STING, thereby promoting a pro-inflammatory senescence-associated secretory phenotype (SASP) and facilitating chronic infection and tissue damage. By linking microbial activity with cellular aging processes, this work offers a novel perspective on the contribution of infections to premature aging and age-related diseases and highlights potential therapeutic targets for modulating senescence and improving host resilience.