Age-associated reductions in hair tensile resistance were accompanied by lower cortical disulfide bond content and changes in follicular COCH expression, suggesting that the gene may be a candidate marker of hair-shaft integrity.
Researchers examined newly grown hair from 10 healthy volunteers, including 5 aged 20 to 40 years and 5 aged older than 50 years. Ten strands collected close to the scalp from each participant were bundled for measurement of maximum tensile force. Cortical disulfide bond content was assessed using Raman spectroscopy. Hair from the older participants had over 21% lower disulfide bond content compared with hair from the younger participants. Maximum tensile force was more than 40% lower, decreasing from about 0.012 N in the younger participants to 0.007 N in the older participants. Tensile resistance was positively correlated with disulfide bond content.
The researchers assessed whether follicular gene expression was associated with these differences. In 1 data set, about 14 to 15 follicles from each of 3 donors were stratified by disulfide bond content for transcriptomic analysis. A separate age-related data set included hair follicles from 10 female patients with female-pattern hair loss aged 30 to 62 years. Among 21 genes associated with disulfide bond levels in the first analysis, 14 were available for evaluation of their relationship with age in the second data set.
Transcriptomic profiling identified 19 genes with higher expression and 2 with lower expression in follicles associated with high vs. low disulfide bond content. COCH, KCNA2, and SERPINB3 showed the strongest inverse correlations with age among the genes evaluated in the age-related data set, although none remained statistically significant following adjustment for multiple comparisons. COCH and SERPINB3 were prioritized for further evaluation.
The researchers obtained about 30 follicles from each of 2 additional donors and used small interfering RNA to suppress candidate gene expression during 6 days of ex vivo culture. COCH knockdown reduced Raman-detected disulfide bond density in newly formed hair shafts across both biological replicates, whereas SERPINB3 knockdown resulted in a smaller, nonsignificant decrease. Immunohistochemical analysis localized the cochlin protein to the hair matrix, outer root sheath, and emerging hair shaft.
Maximum tensile force represented the resistance of bundled hair shafts under standardized conditions rather than intrinsic elastic modulus, and the measurements were not normalized to cross-sectional area. Although histologic examination showed no apparent differences in shaft morphology between age groups, hair-shaft diameter was not quantitatively measured, so differences in geometry could not be excluded as contributors to the observed force measurements.
Other limitations included the small clinical and transcriptomic cohorts and substantial interparticipant variation. The discovery and validation cohorts differed in sex, disease context, scalp region, and sample size. Ex vivo follicle cultures could not reproduce the full complexity of in vivo follicular signaling and systemic influences. The COCH knockdown experiment represented initial functional validation rather than definitive mechanistic evidence. Rescue experiments or other complementary approaches are needed.
“COCH should be carefully framed as a prioritized candidate marker that requires extensive validation in larger cohorts to fully establish its clinical applicability,” wrote lead study author Hyun Woo Joo, of the Department of Immunology at the Kyungpook National University School of Medicine in South Korea, and colleagues.
The study authors reported no conflicts of interest.
Source: Experimental Dermatology