Cellular Quiescence Displays a Transcriptional Inflammatory Phenotype Similar to the One in Cellular Senescence [bulk RNA-seq]

Cellular senescence, traditionally viewed as the irreversible arrest of proliferating cells in response to stress and DNA damage, is a key mechanism underlying cellular aging. Several studies have identified a process called ”quiescence-origin senescence,” where quiescent cells bypass proliferation and transition directly into senescence. In this context, we introduce the concept of the transcriptional Quiescence-Associated Secretory Phenotype (tQASP), a putative inflammatory secretory profile that arises in human quiescent cells and may serve as a precursor to the full senescence-associated secretory phenotype (SASP). We report that quiescent cells express tQASP genes in a cell-type-, induction-dependent manner and that this response is influenced by environmental oxygen levels. tQASP expression is also increased in tissue affected by Idiopathic Pulmonary Fibrosis (IPF) and shows a positive correlation with myofibroblast activation. Together, these data support the concept of a continuum between quiescence and senescence and suggest that the tQASP may be an early marker of cellular aging, with significant implications for tissue homeostasis, aging, cancer, and disease progression.