Age-related patterns of senescence markers immunoexpression in female human epidermis

Cellular senescence contributes to skin aging, but its accumulation during predominantly intrinsic aging remains incompletely characterized, particularly in female skin. This study investigated age-associated epidermal changes and complementary senescence-related markers in photoprotected infra-areolar skin from women undergoing mammoplasty. Samples from 35 participants were divided into Group I (18-29 years, n = 12), Group II (30-49 years, n = 13), and Group III (50-70 years, n = 10). Paraffin sections were evaluated histologically and by immunostaining for lamin B1, β-galactosidase (β-gal), p16INK4a, 4-hydroxy-2-nonenal (4-HNE), and high-mobility group box 1 (HMGB1). Aging was associated with epidermal thinning and flattening of the dermal-epidermal junction. Lamin B1 staining at the nuclear envelope progressively shifted toward lower scores, with an increase in score 1 cells and decreases in score 2 and 3 cells. The proportion of β-gal-positive cells increased significantly with age in both the basal-suprabasal and spinous-granular epidermal compartments. p16INK4a-positive epidermal cells also increased significantly across age groups, while 4-HNE immunoreactivity became more intense and widespread. Conversely, nuclear HMGB1 progressively decreased and was rare or absent in Group III. Together, these concordant changes support the progressive development of a senescence-associated phenotype in photoprotected female infra-areolar epidermis during aging. The use of complementary markers strengthens this interpretation because individual findings may also reflect epidermal differentiation, oxidative damage, or lysosomal content. However, the anatomical specificity of infra-areolar skin limits generalization to other intrinsically aged skin sites.