Autophagy and Stem Cell Aging: Implications for Oral Tissue Regeneration

Chronic stress can cause cellular damage that leads to cell aging and ultimately tissue/organ aging. Autophagy, a cellular process that eliminates damaged components, is closely associated with cell aging. Decreased autophagy is linked to age-related pathologies, while enhanced autophagy has been shown to extend lifespan and delay aging features. Manipulating autophagy to decrease aging features in stem cells may benefit oral tissue regeneration, as some oral diseases are more prevalent in older individuals.

While autophagy's role in oral tissue-related stem cells is limited, studies have shown that enhancing autophagy with metformin or melatonin can decrease senescence-related gene expression and promote regeneration in periodontal tissue. Autophagy is required for recycling long-lived proteins and organelles in other stem cells, such as embryonic stem cells, BMMSCs, hematopoietic stem cells, and neuronal stem cells. In quiescent stem cells, basal autophagy levels are high to maintain their self-renewal activity, while aging decreases regenerative function by breaking their proteostasis, mitochondrial function, and oxidative balance. High-autophagy stem cells have long-term regeneration potential, while reestablishing autophagy can reverse senescence and restore regenerative functions in aging stem cells.