Skin aging is fundamentally a breakdown in cellular quality control rather than a strictly aesthetic phenomenon. To address this, the present conceptual review provides an interdisciplinary analysis of the biological foundations of skin aging, spotlighting ubiquitination as the master regulator of proteostasis. Complex, interdependent mechanisms are responsible for protecting skin cells, mediating crucial interplay between the ubiquitin-proteasome system (UPS), autophagy, and molecular chaperones. By examining how the UPS governs proliferation, oxidative stress responses, and inflammation, the consequences of its age-related dysregulation become evident. Bridging advanced cell biology with regenerative dermatology, the presented analysis pivots away from direct pharmacological modulation. Instead, it emphasizes biologically grounded strategies to protect and stabilize the cellular environment. In conclusion, the review establishes a “well-aging” paradigm that integrates cutting-edge proteostasis research with practical applications for cosmetic formulation design and proactive skincare.
Ziombra et al. (Tue,) studied this question.