Aging and the emerging role of cellular senescence in osteoarthritis

Diekman BO, Loeser RF · Osteoarthritis Cartilage

Finds every proposed hallmark of ageing documented in articular cartilage, telomere attrition among them: mean chondrocyte telomere length shortens with age and correlates with senescence-associated beta-galactosidase, and telomerase overexpression avoids chondrocyte senescence only when cell-cycle inhibitors are also inactivated. On therapy: the intra-articular senolytic UBX0101 reduced osteoarthritis features and pain in 10-week-old mice, was less effective at 72 weeks, and in a phase 2 trial in adults with symptomatic knee osteoarthritis did not reduce pain or improve function at 12 weeks; oral fisetin is in a phase 1/2 knee trial (NCT04210986) with results unreported; metformin users with type 2 diabetes had lower incident osteoarthritis but not fewer joint replacements; raising NAD+ by CD38 inhibition reduced osteoarthritis severity in a preclinical model.

Population

Narrative review of the twelve hallmarks of ageing as they appear in joint tissues, and of cellular senescence as a therapeutic target in osteoarthritis

Intervention

n/a

Comparator

n/a

Limitations

Narrative review; the archived text is the accepted author manuscript rather than the typeset version. Funded by the US National Institute on Aging, which had no role in the content. Most human tissue data come from end-stage surgical waste, which the authors note cannot separate what precedes osteoarthritis from what follows it.