Stress-Sensing in the Human Greying Hair Follicle: Ataxia Telangiectasia Mutated (ATM) Depletion in Hair Bulb Melanocytes in Canities-Prone Scalp

The study investigated the role of oxidative stress in hair greying (canities) by examining the follicular melanin unit in aging human scalp hair follicles from individuals aged 22–70 years. The researchers focused on over 20 markers related to melanocytes, apoptosis, cell cycle, DNA repair/damage, senescence, and oxidative stress. They found a reduction in melanocyte-specific markers correlating with the extent of canities and discovered intense nuclear expression of Ataxia Telangiectasia Mutated (ATM) protein, which is activated by DNA damage and functions as an oxidative stress sensor, within melanocytes of anagen hair follicle bulbs. The expression of ATM correlated with the pigmentary status of canities-affected hair follicles. Increased staining of redox-associated markers was observed in bulbar melanocytes, but no specific change in other oxidative stress markers was detected when compared to surrounding keratinocytes. However, distinct expression patterns for oxidative stress and apoptosis/differentiation markers were found in the inner root sheath and other hair follicle parts. In vitro experiments showed that ATM expression increased with hydrogen peroxide exposure and was prevented by antioxidants. Inhibition of ATM expression led to a loss of melanocyte viability under oxidative stress. These findings suggest that ATM plays a crucial role in protecting hair follicle melanocytes from oxidative stress/damage and underscores the complexity of redox sensing in hair follicle pigmentation and growth.