The Oncologic Ambivalence of Longevity Interventions in Photoaged Skin

ABSTRACT Longevity‐associated interventions increasingly enter dermatologic practice, including in skin shaped by chronic ultraviolet (UV) exposure. This narrative review evaluates their potential oncologic relevance in photoaged skin and field cancerization. We distinguish three evidence levels: demonstrated clinical effects, biologically plausible risks supported by mechanistic or translational data, and theoretical considerations without direct clinical validation. Direct human evidence that longevity interventions increase skin cancer risk is currently lacking. Preclinical and translational studies nevertheless show that stress‐response pathways, including autophagy and NAD + ‐dependent networks, may have context‐ and stage‐dependent effects: damage control may be beneficial in healthy tissue, whereas established malignant cells can exploit the same pathways for survival. Clinically, nicotinamide is distinct from nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) because randomised trial data support temporary chemopreventive benefit in selected high‐risk patients. For most other interventions, dermatologic‐oncologic efficacy and long‐term safety remain unproven. Counselling should therefore prioritise photoprotection, surveillance, lesion‐directed or field‐directed treatment and substance‐specific evidence. Biological plausibility alone should neither be interpreted as proof of harm nor used to claim cancer prevention.