Review of senescence-associated secretory phenotype in aging osteoarthritis and disc degeneration

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Frontiers in Medicine Published May 18, 2026 Medically reviewed May 18, 2026 DOI ↗ By Dr. Sofia Müller, MD · Lifespan & Whole-Person Care

Key Takeaway

Note that this review offers a framework for future research on SASP in aging bone and joint conditions.

This publication is a narrative review focusing on the senescence-associated secretory phenotype (SASP) within the context of aging populations. The scope covers conditions including osteoarthritis, intervertebral disc degeneration, and osteoporosis. The authors do not report a specific sample size, setting, or primary outcomes for the underlying studies discussed. Instead, the review synthesizes qualitative arguments regarding the biological mechanisms of SASP in these degenerative states.

The authors explicitly identify several limitations inherent to the current evidence base. These include tissue heterogeneity, challenges with biomarker selection, issues regarding delivery specificity, safety concerns, and trial design constraints. The review does not provide specific numerical data, p-values, or confidence intervals because the source is a synthesis rather than a primary trial.

The practice relevance of this work is described as providing a more clinically actionable framework for future mechanistic and translational research. The text does not report specific adverse events, discontinuations, or tolerability data. Readers should interpret these findings as a conceptual overview rather than definitive clinical guidance for immediate patient management.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedMay 2026

View Original Abstract ↓

Orthopedic degenerative diseases, including osteoarthritis (OA), intervertebral disc degeneration (IVDD), and osteoporosis (OP), are major causes of chronic pain and functional decline in aging populations worldwide. The senescence-associated secretory phenotype (SASP), a downstream but central effector of cellular senescence, has emerged as a key pathogenic mediator that links senescent cell accumulation to tissue degeneration in the musculoskeletal system. Comprising pro-inflammatory cytokines, chemokines, matrix-degrading enzymes, growth factors, and extracellular vesicle-associated signals, SASP disrupts orthopedic tissue homeostasis through several interconnected mechanisms, including chronic sterile inflammation, extracellular matrix (ECM) catabolism, paracrine senescence propagation, stem/progenitor cell dysfunction, and, in selected contexts, aberrant neurovascular remodeling. In this review, we focus on the tissue-specific roles of SASP in major orthopedic degenerative diseases and organize current evidence according to mechanism-to-disease and mechanism-to-therapy relationships. We further summarize mechanism-linked therapeutic strategies, including senolytics, senomorphics, autophagy-based interventions, and emerging gene-/RNA-targeted approaches, while distinguishing between established preclinical avenues and exploratory modalities. Finally, we highlight key barriers to clinical translation, including tissue heterogeneity, biomarker selection, delivery specificity, safety, and trial design, to provide a more clinically actionable framework for future mechanistic and translational research.