Mayo Clin Proc. 2025 Sep 30. pii: S0025-6196(25)00416-1. [Epub ahead of print]
Skin aging is an inherent biological component of human aging. As the global population ages, the incidence of age-related skin conditions has become increasingly prevalent. Both intrinsic and extrinsic factors, collectively known as the skin "exposome," contribute to visible and physiological changes. The skin's layers, including the epidermis, dermis, and hypodermis, function both independently and interdependently in these aging processes. Intrinsic factors such as hormonal fluctuations, genetic predispositions, and cellular senescence, defined as an irreversible cell cycle arrest, drive physiological age-related skin changes. These changes are underpinned by several interconnected hallmarks of aging, including genomic instability, telomere attrition, epigenetic alterations, and loss of proteostasis, all of which impair cell renewal and dermal structure. Stem cell exhaustion and mitochondrial dysfunction reduce the skin's capacity to regenerate and adapt to stress, whereas altered intercellular communication and chronic low-grade inflammation ("inflammaging") further accelerate aging phenotypes such as loss of elasticity, epidermal thinning, and delayed wound healing. Extrinsic factors, including ultraviolet radiation, air pollution, smoking, and poor nutrition, compound these effects by increasing oxidative stress, DNA damage, and activating senescence-associated secretory phenotypes. Lifelong sun protection, nutritious dietary habits, regular physical activity, and topical interventions such as sunscreen and moisturizers help maintain a resilient skin microenvironment. This review highlights the urgent need to recognize, prevent, and treat skin aging. Emerging therapies targeting root-cause mechanisms may revolutionize dermatologic care and extend skin healthspan - now known as skinspan.