Abstract

Objectives: To evaluate the clinical relevance and biological rationale of a dual‑level anti‑aging strategy combining systemic activation of the NAD⁺/sirtuin metabolic pathway with localized dermal biostimulation using polynucleotide injectables. The objective was to determine whether metabolic priming enhances fibroblast responsiveness and improves global skin quality outcomes. Introduction: Skin aging results from mitochondrial decline, impaired DNA repair, ECM degradation and chronic inflammation. A key upstream driver is NAD⁺ depletion, which weakens sirtuin‑mediated genomic stability, mitochondrial function and oxidative stress control. Polynucleotides complement this pathway by activating A2A receptors, enhancing fibroblast activity, ECM synthesis and tissue hydration. Combining metabolic activation with dermal biostimulation may offer synergistic benefits for skin longevity. Materials / method: Adults aged 35–65 with visible facial aging followed a 4–8‑week combined protocol: oral NAD⁺/sirtuin metabolic activation and 2–3 intradermal sessions with polynucleotide injectables. Outcomes included cutometry for elasticity, corneometry for hydration, and high‑frequency ultrasound for dermal density. Standardized photography and patient‑reported evaluations were collected as secondary measures. Results: Three cases showed consistent improvement. Patient A reported +18% elasticity and +22% hydration, with reduced micro‑roughness and redness. Patient B showed a +15% increase in dermal density and better mandibular contour. Patient C demonstrated greater radiance, smoother texture and fewer fine lines. Metabolic activation appeared to prime fibroblasts, enhancing their response to polynucleotide‑driven ECM remodeling. Conclusion: This integrated metabolic‑regenerative strategy represents a promising frontier in preventive aesthetic medicine. The combination of systemic NAD⁺/sirtuin pathway enhancement with polynucleotide‑based dermal biostimulation offers a biologically coherent, synergistic, and clinically meaningful approach to improving skin quality and promoting long‑term dermal longevity.