To determine the time sequence of biochemical and structural events associated with, and hypothesized to underlie, age-associated tensile weakening of macroscopically normal adult human articular cartilage of the knee.

Macroscopically normal human articular cartilage of the lateral and medial femoral condyles (LFC and MFC) from Young (21–39 yrs), Middle (40–59 yrs), and Old (≥60 yrs) age donors were analyzed for tensile properties, surface wear, and cell and matrix composition.

Variations in tensile, compositional, and surface structural properties were indicative of early, intermediate, and late stages of age-associated cartilage deterioration, occurring at an earlier age in the MFC than the LFC. Differences between Young and Middle age groups (indicative of early-to-intermediate stage changes) included decreased mechanical function in the superficial zone, with a loss of (or low) tensile integrity, and surface wear, with faint striations and mild staining on the articular surface after application of India ink. Differences between Middle and Old age groups (indicative of intermediate-to-late stage changes) included maintenance of moderate level biomechanical function, a decrease in cellularity, and a decrease in matrix glycosaminoglycan content. Tissue fluorescence increased steadily with age.

Many of these age-associated differences are identical to those regarded as pathological features of cartilage degeneration in early osteoarthritis. These findings provide evidence for the roles of mechanical wear, cell death, and enzymatic degradation in mediating the progression through successive and distinguishable stages of early cartilage deterioration.