Age-specific functional epigenetic changes in p21 and p16 in injury-activated satellite cells.

The regenerative capacity of muscle dramatically decreases with age because old muscle stem cells fail to proliferate in response to tissue damage. Here, we uncover key age-specific differences underlying this proliferative decline: namely, the genetic loci of cyclin/cyclin-dependent kinase (CDK) inhibitors (CDKIs) p21 and p16 are more epigenetically silenced in young muscle stem cells, as compared to old, both in quiescent cells and those responding to tissue injury. Interestingly, phosphorylated ERK (pERK) induced in these cells by ectopic FGF2 is found in association with p21 and p16 promoters, and moreover, only in the old cells. Importantly, in the old satellite cells, FGF2/pERK silences p21 epigenetically and transcriptionally, which leads to reduced p21 protein levels and enhanced cell proliferation. In agreement with the epigenetic silencing of the loci, young muscle stem cells do not depend as much as old on ectopic FGF/pERK for their myogenic proliferation. In addition, other CDKIs, such asp15(INK4B) and p27(KIP1) , become elevated in satellite cells with age, confirming and explaining the profound regenerative defect of old muscle. This work enhances our understanding of tissue aging, promoting strategies for combating age-imposed tissue degeneration.

Resected femoral anthropometry for design of the femoral component of the total knee prosthesis in a Korean population.

We measured the mediolateral (ML) and anteroposterior (AP) length, height and widths of the anterior, posterior and inferior section of the resected distal femurs using three dimensional computer tomographic measurements in 200 knees from 100 cadavers. We also calculated the aspect ratio (ML/AP) and compared the measured parameters with that of six conventionally used total knee femoral prostheses. We found that the average ML (70.2±5.5 mm) and AP (53.9±3.8 mm) dimensions from our study were lower than those reported from Western populations. The aspect ratio showed a progressive decline with an increasing antero-posterior dimension. All of the compared designs showed undersizing for the mediolateral dimension distally and for the widths of the resected medial and lateral posterior femoral condyles. But some of the compared designs showed oversizing for the height of the resected medial and lateral posterior femoral condyles. This study provides guidelines for designing a suitable femoral component for total knee prostheses that fit Asian populations.