- Knee osteoarthritis is a phenotype-dependent manifestation of joint ageing driven by cellular senescence, inflammaging, mitochondrial dysfunction, synovitis, vascular remodelling, and impaired repair.
- Weight reduction, exercise, and education are core interventions with consistent evidence for pain reduction, improved function, and beneficial systemic effects on inflammation and metabolism.
- Analgesics and intra-articular agents mainly modulate symptoms; platelet-rich plasma and cell therapies lack long-term structural data; GAE plausible but sham-controlled evidence inconsistent.
Geroscience. 2026 Aug 10. doi: 10.1007/s11357-026-02467-6. Online ahead of print.
ABSTRACT
Knee osteoarthritis (KOA) is a leading cause of late-life pain, mobility loss, and disability, and is increasingly recognized as a phenotype-dependent manifestation of joint aging rather than a purely mechanical disorder. Cellular senescence, inflammaging, mitochondrial dysfunction, synovial inflammation, vascular remodeling, and impaired repair capacity converge to shape KOA symptoms and progression. This narrative review synthesizes evidence on conservative and minimally invasive KOA therapies within a geroscience-guided, phenotype-informed framework. A structured search of PubMed/MEDLINE and Embase from January 2010 to May 2026 identified randomized trials, meta-analyses, guidelines, position statements, and high-quality observational studies evaluating lifestyle interventions, pharmacologic and nutritional strategies, intra-articular therapies, genicular nerve ablation, and genicular artery embolization (GAE). Weight reduction, exercise, and education remain core joint healthspan interventions, with consistent evidence for pain reduction, functional benefit, and favorable systemic effects on inflammation and metabolism. Pharmacologic analgesia, intra-articular corticosteroids, and hyaluronic acid are best interpreted as symptom modulators, while platelet-rich plasma, autologous conditioned serum, and mesenchymal stromal/stem cell-based approaches remain limited by heterogeneity and insufficient long-term structural data. Genicular nerve ablation may support functional longevity through pain control without structural modification. GAE is biologically plausible for synovitis/hypervascularity-dominant KOA, but sham-controlled evidence remains inconsistent. Future trials should distinguish symptomatic relief from true modification of joint aging biology.
PMID:42576130 | DOI:10.1007/s11357-026-02467-6
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