Single‐Nucleus Transcriptomic Atlas of Human Vellus Hair Pilosebaceous Units Reveals Age‐Associated Remodeling

ABSTRACT

The pilosebaceous units (PSUs) are essential micro‐organs for skin homeostasis, yet human vellus hair‐associated PSUs remain largely understudied. Here, we present a single‐nucleus transcriptomic atlas of PSUs from the back skin of healthy young and aged males, revealing extensive age‐associated cellular and transcriptional remodeling within this niche. We show that aging is accompanied by reduced relative representation of bulge hair follicle stem cells, together with altered regeneration‐associated transcriptional programs. Sebocytes display enhanced androgen responsiveness coupled with increased lipid biosynthetic activity during aging. Concurrently, an ion channel‐enriched follicular population shows increased representation with age and exhibits stress‐ and inflammation‐associated transcriptional features. In parallel, an innate immune‐like melanocyte subset shows reduced relative representation during aging, coinciding with changes in inferred melanocyte–immune communication. Notably, immune subsets in aged PSUs display coordinated changes in metabolic pathway signatures, suggesting an association between immune remodeling and metabolic state. Together, our findings highlight the aged PSU as a focal site where epithelial, immune, and metabolic alterations converge during skin aging. This work establishes a comprehensive single‐nucleus atlas of human vellus PSU aging and provides a framework for understanding how aging reshapes pilosebaceous niche biology, with potential implications for age‐associated cutaneous inflammation and dysfunction.