Periodontal Ligament Stem Cell Aging in Age-Related Orthodontic Changes: Mechanisms and Rescue Strategies

With the growing demand for adult orthodontic treatment, age-related changes in clinical outcomes have emerged as significant challenges. However, effective strategies to improve outcomes in aging patients remain limited. Periodontal ligament stem cells (PDLSCs), a mechanosensitive subpopulation of mesenchymal stem cells, play a significant role in bone remodeling during orthodontic tooth movement (OTM) and are increasingly recognized as key contributors to the decline in orthodontic responsiveness with age. This review highlights the multifaceted role of PDLSCs in OTM, encompassing mechanosensation, mechanotransduction, and subsequent bone remodeling. It further examines how aging impairs PDLSC biology and potentially contributes to reduced orthodontic responsiveness in older individuals. Key aging-related mechanisms are described, including increased oxidative stress, disrupted mitochondrial homeostasis, impaired autophagy, loss of proteostasis, and epigenetic modifications. Dysregulation of intracellular signaling pathways further underscores the complexity of age-related functional decline. Based on these insights, emerging strategies for rescuing aged PDLSCs are summarized, offering a theoretical foundation for developing targeted interventions to enhance orthodontic outcomes in the aging population.