Age-Related KLHL22 Expression in Human MSCs and Regenerative Implications

Abstract

Aging in human bone marrow-derived mesenchymal stromal cells (hMSCs) affects their regenerative capabilities and therapeutic efficacy, which are critical for successful cell-based regeneration therapies. In this study, we aimed to identify genetic markers of aging in hMSCs to better understand the impact of donor age on cell function. We conducted analysis on data from genome-wide microarray analysis on early-passage hMSCs isolated from the bone marrow of 61 donors aged between 17 and 84 years found in the GSE39540 public dataset. One such gene, identified as KLHL22 (ENSG00000099910), showed a significant negative correlation with age (p=0.032), with a regression slope of -0.0089 indicating decreased expression in older donors. The R2R2 value of 0.243 suggests that approximately 24.3% of the expression variability of this gene can be explained by age. These findings are consistent with the known decline in tissue maintenance and regeneration capabilities in aging hMSCs and may reflect broader aging processes impacting cell-based therapies. Our results provide insight into the molecular basis of aging in hMSCs and highlight the potential of using gene expression profiles as markers to select more potent hMSCs for therapeutic applications. This gene signature could serve as a foundation for developing strategies to rejuvenate aged hMSCs, enhancing the efficacy of regenerative therapies.