A 15-Year Computational Twin Modeling Study of Botulinum Toxin A Frequency and Age-Related Facial Aging

Facial aging results from intrinsic biologic decline and extrinsic environmental influences, producing progressive changes in skin structure, collagen integrity, and soft-tissue support. Botulinum neurotoxin type A (BoNTA) is widely used to mitigate dynamic wrinkles, yet the long-term interplay between treatment frequency, age at initiation, and structural aging outcomes remains unclear.

A 15-year in silico study was performed using digital twin facial models (AesthetiSIM^TM) stratified by age at BoNTA initiation (20-30, 31-40, and 41-50 years) and injection frequency (biannual vs triannual). Six structural aging metrics were evaluated: forehead, glabellar, and lateral canthal wrinkle depth; collagen density; dermal thickness; and facial sag index (FSI). Measurements were taken at baseline, year 5, year 10, and year 15.

Wrinkle depth decreased in all groups during the first five years, with early initiators on triannual regimens showing the largest short-term reductions (e.g., glabellar lines depth decreased from 0.833 to ~0.719 mm). However, by year 15, wrinkle depths rebounded and converged across all cohorts (~1.0 mm). Dermal thickness declined progressively, from ~1.89 mm in the youngest cohort at baseline to ~1.75 mm by year 15, with minimal differences between treatment frequencies. Collagen density fell steadily from ~ 56.048 mg/cm² at baseline to ~ 44.030-46.030 mg/cm² in all groups by year 15. FSI ranged from 0.73-1.20 cm² at baseline to 1.19-1.32 cm² at year 15. Across all measures, differences between age cohorts and injection frequencies were small and not sustained over time.

Over a 15-year simulation, continuous BoNTA treatment produced measurable wrinkle reduction during the first five years, particularly in younger cohorts. However, beyond this early phase, no cumulative structural benefits were sustained. By year fifteen, wrinkle depth, dermal thickness, collagen density, and facial sag were virtually indistinguishable across all dosing schedules. These findings demonstrate that while BoNTA effectively softens dynamic lines in the short term, it does not alter the underlying trajectory of intrinsic aging. Long-term facial outcomes appear governed primarily by biological and cellular decline rather than by treatment frequency or age at initiation. Although digital twin modeling provides controlled and reproducible insights, these results must be validated through robust, long-term prospective studies involving diverse, multiethnic human populations to ensure their generalizability and clinical relevance.

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .