Cellular senescence signaling pathway

Cellular senescence signaling pathways encompass a variety of molecular cascades that converge to enforce stable cell cycle arrest in response to diverse stresses such as DNA damage, telomere shortening, oncogenic activation, or oxidative stress[1][3]. The principal canonical pathways include the p53/p21^CIP1^ and p16^INK4A^/pRb tumor suppressor axes, which block cell cycle progression and prevent proliferation of damaged or pre-neoplastic cells[1][3][4]. Additional interconnected pathways regulating or responding to senescence include insulin/IGF-1, mTOR, AMPK, NF-κB, MAPKs, and Sirtuins[2][4]. Senescent cells often develop a senescence-associated secretory phenotype (SASP), producing pro-inflammatory cytokines, growth factors, and proteases that can have both beneficial and detrimental effects on tissue environment[3]. Dysregulation or persistence of senescent signaling contributes to aging, cancer, chronic inflammation, and various degenerative diseases[1][2]. "Cellular senescence signaling pathways" is not a druggable target per se, but a collection of regulation nodes and processes that together constitute an important biological concept and therapeutic field[3]. It is not a protein, receptor, transporter, or well-defined molecular entity. The correct approach for therapeutic targeting involves focusing on specific pathway components (e.g., p53, p16^INK4A^, mTOR), not on "cellular senescence signaling pathways" as a single target.

Other names

Senescence signaling pathwaysCellular senescence pathwaysSenescence regulatory pathways

Inhibition or clearing of senescent cells (senolysis); Modulation of DDR pathways (p53, p21, p16, Rb); Inhibition of mTOR signaling; Activation of AMPK; Modulation of NF-κB and SASP.