The critical role and mechanism of the topography of materials to regulate the function and fate of mesenchymal stem cells are reported.

As global aging accelerates, the prevention and treatment of age-related bone diseases are becoming a critical issue. In the process of senescence, bone marrow mesenchymal stem cells (BMSCs) gradually lose the capability of self-renewal and functional differentiation, resulting in impairment of bone tissue regeneration and disorder of bone tissue homeostasis. Alteration in epigenetic modification is an essential factor of BMSC dysfunction during aging. Its transferability and reversibility provide the possibility to combat BMSC aging by reversing age-related modifications. Emerging evidence demonstrates that epigenetic therapy based on aberrant epigenetic modifications could alleviate the senescence and dysfunction of stem cells. This review summarizes potential therapeutic targets for BMSC aging, introduces some potential approaches to alleviating BMSC aging, and analyzes its prospect in the clinical application of age-related bone diseases.

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus, marked by progressive renal damage. Recent evidence indicates that metabolic reprogramming is crucial to DN pathogenesis, yet its underlying mechanisms are not well understood. This study aimed to examine how metabolic reprogramming-related genes (MRRGs) are differentially expressed and to explore their potential mechanisms in the development of DN. We analyzed the datasets GSE30528 and GSE96804 from the Gene Expression Omnibus (GEO), comprising 50 DN samples and 33 controls. MRRGs were sourced from GeneCards and PubMed. Data preprocessing included batch effect correction using the R package sva, followed by normalization and differential expression analysis with limma (|logFC|> 0.5, adj.p < 0.05). Functional enrichment analyses (GO, KEGG, GSEA) were performed using clusterProfiler. Protein–protein interaction (PPI) networks were constructed via STRING, identifying hub genes through CytoHubba. Regulatory networks (mRNA-TF, mRNA-miRNA) were derived from ChIPBase and StarBase. Validation of hub genes and ROC analysis assessed diagnostic performance. ssGSEA quantified immune cell infiltration. Our analysis identified 708 differentially expressed genes (DEGs), including 119 metabolic reprogramming-related DEGs (MRRDEGs). Enrichment analyses revealed significant roles for MRRDEGs in processes such as wound healing and pathways like MAPK signaling. The PPI network identified nine hub genes: FN1, CD44, KDR, EGF, HSPG2, HGF, FGF9, IGF1, and ALB, which exhibited high diagnostic accuracy (AUC 0.7 to 0.9). Notably, FN1 and CD44 showed significant association with renal fibrosis and could serve as potential biomarkers for early diagnosis and therapeutic targets in DN. Immune infiltration analysis showed notable differences in immune cell composition between DN and control samples. This study identifies hub genes such as FN1 and CD44, with potential diagnostic value in DN. It also reveals immune cell infiltration differences between DN patients and controls, offering insights into disease progression and potential therapeutic targets.

Stem cell senescence and exhaustion, a hallmark of aging, lead to declines in tissue repair and regeneration in aged individuals. Emerging evidence has revealed that epigenetic regulation plays critical roles in the self-renew, lineage-commitment, survival, and function of stem cells. Moreover, epigenetic alterations are considered important drivers of stem cell dysfunction during aging. In this review, we focused on current knowledge of the histone modifications in the aging of mesenchymal stem cells (MSCs). The aberrant epigenetic modifications on histones, including methylation and acetylation, have been found in aging MSCs. By disturbing the expression of specific genes, these epigenetic modifications affect the self-renew, survival, and differentiation of MSCs. A set of epigenetic enzymes that write or erase these modifications are critical in regulating the aging of MSCs. Furthermore, we discussed the rejuvenation strategies based on epigenetics to prevent stem cell aging and/or rejuvenate senescent MSCs.