Decoding Dental Stem Cell Aging: Mechanisms, Therapeutic Strategies, and Beyond

Area of Science:

• Regenerative Medicine
• Stem Cell Biology
• Gerontology

Background:

• Dental stem cells (DSCs) possess significant regenerative potential due to their proliferative, differentiation, and immunomodulatory capacities.
• The aging process critically diminishes DSC functionality, hindering their clinical application in regenerative therapies.
• Understanding age-related decline in DSCs is vital for developing effective rejuvenation strategies.

Purpose of the Study:

• To systematically review the mechanisms of DSC aging, including signaling pathways, metabolic dysregulation, and epigenetic changes.
• To identify intrinsic and extrinsic factors contributing to DSC aging and their impact on regenerative potential.
• To explore therapeutic strategies for mitigating age-related functional decline in DSCs and discuss clinical translation challenges.

Main Methods:

• Systematic literature review focusing on cellular and molecular mechanisms of DSC aging.
• Analysis of disrupted signaling pathways, metabolic dysregulation, epigenetic modifications, and non-coding RNA roles.
• Investigation of intrinsic (cellular) and extrinsic (systemic) factors influencing DSC senescence.

Main Results:

• Aging disrupts key signaling pathways, induces metabolic dysregulation, and causes epigenetic modifications in DSCs.
• Non-coding RNAs and critical proteins play regulatory roles in DSC aging.
• Intrinsic and extrinsic factors significantly contribute to the functional decline of aged DSCs.

Conclusions:

• Targeting extracellular matrix, mitochondrial dysfunction, and molecular pathways offers potential for rejuvenating aged DSCs.
• Inter-individual variability and systemic influences present challenges for clinical translation of DSC-based therapies.
• Multidisciplinary approaches are essential to enhance therapeutic outcomes and advance the clinical use of DSCs in regenerative medicine for aging populations.