The article reviews the mechanisms and therapeutic strategies for the senescence-associated secretory phenotype (SASP) in the context of intervertebral disc degeneration (IVD). Cellular senescence, a state of permanent cell cycle arrest, is a significant factor in aging and age-related diseases. SASP, a secretory ensemble produced by senescent cells, creates an inflammatory and catabolic environment, leading to tissue degeneration. The accumulation of senescent cells and the continuous release of SASP impede disc homeostasis and hinder tissue regeneration, making it a significant challenge in treating IVD degeneration. The article highlights the key mediators and regulatory mechanisms of SASP, including inflammatory cytokines, matrix metalloproteinases (MMPs), growth factors, chemokines, and epigenetic factors. These components modulate cellular conditions through autocrine and paracrine signaling, leading to cellular senescence and tissue imbalance. The p53/p21 and p16/Rb pathways, mTOR, AMPK, NF-κB, and cGAS-STING signaling pathways are crucial for regulating SASP and cellular senescence. Therapeutic strategies targeting SASP and cellular senescence include the use of natural products and their analogues, Bcl-2 family inhibitors, HSP90 inhibitors, and p53-based therapies. Natural compounds like quercetin, curcumin, and dehydrocostus lactone have shown anti-aging properties and can modulate SASP expression. Bcl-2 family inhibitors promote apoptosis in aged cells, while HSP90 inhibitors target molecular chaperones involved in cellular aging. P53-based therapies, such as RG7112, aim to revive p53 activity and induce apoptosis in senescent cells. The article concludes by emphasizing the need for a deeper understanding of the underlying mechanisms of cellular senescence to develop effective therapeutic strategies for IVD degeneration. While preclinical studies have shown promising results, challenges remain in terms of cell selectivity and potential side effects of anti-aging therapies.The article reviews the mechanisms and therapeutic strategies for the senescence-associated secretory phenotype (SASP) in the context of intervertebral disc degeneration (IVD). Cellular senescence, a state of permanent cell cycle arrest, is a significant factor in aging and age-related diseases. SASP, a secretory ensemble produced by senescent cells, creates an inflammatory and catabolic environment, leading to tissue degeneration. The accumulation of senescent cells and the continuous release of SASP impede disc homeostasis and hinder tissue regeneration, making it a significant challenge in treating IVD degeneration. The article highlights the key mediators and regulatory mechanisms of SASP, including inflammatory cytokines, matrix metalloproteinases (MMPs), growth factors, chemokines, and epigenetic factors. These components modulate cellular conditions through autocrine and paracrine signaling, leading to cellular senescence and tissue imbalance. The p53/p21 and p16/Rb pathways, mTOR, AMPK, NF-κB, and cGAS-STING signaling pathways are crucial for regulating SASP and cellular senescence. Therapeutic strategies targeting SASP and cellular senescence include the use of natural products and their analogues, Bcl-2 family inhibitors, HSP90 inhibitors, and p53-based therapies. Natural compounds like quercetin, curcumin, and dehydrocostus lactone have shown anti-aging properties and can modulate SASP expression. Bcl-2 family inhibitors promote apoptosis in aged cells, while HSP90 inhibitors target molecular chaperones involved in cellular aging. P53-based therapies, such as RG7112, aim to revive p53 activity and induce apoptosis in senescent cells. The article concludes by emphasizing the need for a deeper understanding of the underlying mechanisms of cellular senescence to develop effective therapeutic strategies for IVD degeneration. While preclinical studies have shown promising results, challenges remain in terms of cell selectivity and potential side effects of anti-aging therapies.