Autophagy and Oral Tissue Regeneration: Potential Therapeutic Strategy for Age-Related Diseases

Autophagy is a cellular process that plays a crucial role in maintaining stem cell function and tissue regeneration. As a sensor of stress, autophagy is closely associated with cell aging, and the decrease of autophagy is involved in the development of age-associated pathologies. Enhanced autophagy extended the life span in several species and delayed the decline features of aging. Considering the prevalence and incidence of some kind of oral diseases are higher in the old, manipulating autophagy to decrease aging features of stem cells may benefit oral tissue regeneration.

The accumulation of cellular damage caused by chronic stresses of small magnitudes induces cell aging, and stem cell aging eventually causes a progressive aggravation of tissue/organ aging. Autophagy affects stem cell activity has been proved in numerous tissue, but it’s function in oral tissue related stem cells is quite finite. Limited studies proved that in PDLSCs, aging decreased the osteogenic differentiation ability of these cells, while enhancing autophagy with metformin or melatonin decreased senescence-related gene expression and exerted beneficial regeneration in periodontal tissue. In other stem cells, such as embryonic stem cells, BMMSCs, hematopoietic stem cells, neuronal stem cells, require autophagy to recycle long-lived proteins or cytoplasmic organelles to eliminate cellular waste. Especially in quiescent stem cells, basal autophagy levels are high to maintain the quiescent state and self-renewal activity, while aging transitions stem cells into an irreversible senescent state and decreases their regenerative function by break their proteostasis, mitochondrial function and oxidative balance. High-autophagy stem cells preserved a low metabolic state with long-term regeneration potential, and reestablishment of autophagy reversed senescence and restored the regenerative functions of aging stem cells.

In conclusion, autophagy plays a crucial role in the maintenance of stem cell function and tissue regeneration. Manipulating autophagy may provide a potential therapeutic strategy for age-related oral diseases by enhancing the regenerative capacity of stem cells. Further studies are needed to explore the mechanisms underlying the regulation of autophagy in oral tissue-related stem cells and its potential therapeutic applications.