Aesthetic medicine is shifting from symptomatic correction to biological structural restoration. Regenerative aesthetics represents a frontier in dermatology, focusing on the restoration of the skin microenvironment to enhance cellular vitality and tissue resilience. Central to this approach is the concept of “skin bed preparation”, a strategic priming phase designed to optimize the physiological terrain before the delivery of advanced aesthetic interventions. This review explores the molecular and cellular mechanisms by which skin bed preparation modulates the extracellular matrix (ECM) and the dermal niche to maximize the efficacy of subsequent treatments and promote long-term skin longevity. Evidence suggests that biostimulatory priming utilizing senolytics, senomorphics, mitochondrial, and/or epigenetic rejuvenators rehabilitates the fibroblast–collagen interactome. By reducing oxidative stress and chronic low-grade inflammation, these preparatory steps transition the skin from a catabolic to an anabolic state. This metabolic reset ensures that subsequent procedures, such as laser therapy, injectable fillers, encounter a responsive cellular environment, resulting in superior collagen induction and prolonged clinical outcomes. Optimizing the skin microenvironment via regenerative aesthetics is not merely an adjunctive step but a fundamental requirement for therapeutic success. Integrating skin bed preparation into clinical protocols provides a synergistic framework that enhances immediate procedural results while addressing the underlying hallmarks of skin aging, ultimately redefining the trajectory of skin health and longevity.

Background/Objectives: Depletion of nicotinamide adenine dinucleotide (NAD⁺) impairs dermal fibroblast function and accelerates skin aging. NAD⁺ precursors such as nicotinamide mononucleotide (NMN) and the reduced form, NADH, are therefore candidate cosmetic actives, but their comparative and combined effects in skin cells remain poorly explored. This in vitro study compared NMN alone, NADH alone, and an NMN + NADH co-formulation. Methods: Human dermal fibroblasts (HDFs) and human mesenchymal stromal cells (hMSCs) were treated with 10 mg/mL of NMN, NADH, or NMN + NADH. Expression of FOXO3, SIRT1, and SIRT3 (HDFs) and NRF2, NOG, and WNT5A (hMSCs) was measured by RT-qPCR, and cellular senescence was quantified by β-galactosidase staining. Results: All treatments increased gene expression relative to untreated controls (p < 0.05), except WNT5A in NMN-treated hMSCs. Increases ranged from 15.4% to 52.3% with NMN, 22.3% to 60.7% with NADH, and 30.5% to 78.1% with NMN + NADH. The co-formulation produced the highest mean expression in every panel and was significantly higher than both single compounds for FOXO3, NRF2, NOG, and WNT5A and higher than NMN for SIRT1; NADH exceeded NMN for NRF2 and WNT5A. The proportion of β-galactosidase-positive HDFs fell from 15.6% in controls to 4.8% (NMN), 3.4% (NADH), and 3.0% (NMN + NADH) (p < 0.01), with no significant differences among treatments. Conclusions: NMN, NADH, and their co-formulation each reduced senescence and modulated longevity-, antioxidant-, and tissue-homeostasis-related genes, with the co-formulation showing the largest transcriptional effects. Because the amount of each active differed between the single compounds and the co-formulation, additive, synergistic, and dose-related effects cannot be distinguished.

Background/Objectives: Cervical integument aging is a complex, multifactorial process characterized by thinning dermis, loss of elasticity, and platysmal band prominence. Multimodal treatments targeting these distinct anatomical layers simultaneously remain limited. This study aimed to evaluate the clinical efficacy, safety, and rejuvenation potential of the STIIM UP Protocol, a single-session treatment combining calcium hydroxyapatite (CaHA), hyaluronic acid (HA), and botulinum toxin type A (BoNT-A) for neck rejuvenation. Methods: This prospective, open-label, exploratory clinical study enrolled 13 healthy women (n = 13) presenting with cervical laxity. The STIIM UP suspension was delivered bilaterally into the subdermal plane of the anterior neck region using a retro-injection fanning technique with a 22G cannula at Day 0 (D0). Evaluated outcomes included the IBSA Neck Grading Scale, Global Aesthetic Improvement Scale (GAIS), FACE-Q module scores, and high-frequency ultrasound (USG) tissue thickness measurements at baseline and Day 120 (D120). Safety was monitored throughout. Results: The median consensus IBSA scores decreased significantly from 4.0 at baseline to 2.0 at both D30 and D120 (p-value < 0.01), indicating a rapid and sustained reduction in laxity. At D120, the GAIS responder rate reached 100% according to independent evaluators and 90.9% based on patient self-assessments. Quantitative USG confirmed statistically significant bilateral tissue thickening across the epidermis, dermis, and subcutaneous strata (p-value < 0.05). Progressive, clinically meaningful improvements were captured via the FACE-Q scales. No local or systemic adverse events were observed. Conclusions: The STIIM UP Protocol is a safe and effective multilayer intervention that successfully achieves comprehensive neck rejuvenation, bridging immediate clinical enhancement with sustained, tissue-proven structural remodeling.