Hallmarks of Aesthetic Ageing: A Proposed Tissue-Level Framework for Facial Aging and Precision Regenerative Aesthetics
Sarit Cohen, Dominik Thor, Atchima Suwanchinda, Shani Levi, Steven CohenAbstract
Background
The Hallmarks of Ageing framework established a biological language for organismal ageing. Facial ageing, however, operates at the tissue level, across anatomically distinct, mechanically coupled and interconnected layers exposed to environmental stressors. These features are not fully captured by systemic ageing models.
Objectives
To propose a tissue-specific translational framework for facial ageing and define priorities for prospective validation.
Methods
An integrative narrative synthesis and translational framework construction approach was used. Candidate hallmarks were selected for relevance to clinically recognisable facial ageing and aesthetic practice. Evidence was appraised for human tissue specificity, mechanistic consistency with ageing biology, and measurable endpoints, and classified into four evidence-maturity tiers.
Results
Ten proposed hallmarks comprise extracellular matrix deterioration, fibroblast senescence, regenerative decline, epigenetic drift, mitochondrial dysfunction, altered intercellular signaling, chronic low-grade inflammation, adipose tissue remodelling, structural support failure, and microvascular decline. They were organised into three tiers: molecular and cellular drivers, stromal and regenerative dysfunction, and structural outcomes. Cross-hallmark synthesis identified evidence-supported convergence on stromal and regenerative dysfunction, selective links to structural outcomes, and reciprocal interactions. Six hallmarks were assigned Tier 1 and four Tier 2; evidence for molecular and niche-level processes in deeper facial compartments was less direct. A multimodal validation strategy links tissue measures to healing, treatment response, durability, and safety.
Conclusions
The framework conceptualises aesthetic ageing as interconnected tissue-level dysfunction rather than isolated phenotypes. Prospective validation should determine whether hallmark-informed assessment adds clinical value beyond anatomical and phenotypic evaluation. If validated, it could support mechanism-informed treatment planning and precision regenerative aesthetics.