Our studies demonstrate that the death of hair follicles involves distinct patterns of expression of active caspases. Active caspase 8, an initiator of the death receptor pathway, was predominately found in the isthmic and upper lower portion of the shaft. This pattern of expression suggests that the death receptor pathway is activated during hair renewal and is initiated by toxic substances that bind to death receptors, i.e., TNF-alpha. Interestingly, activated caspase 3, a downstream effector caspase, was higher in catagen hair then in other phases of the hair cycle, indicating a role in the terminal stage of the apoptotic pathway. Activated caspase 1 was also found in the hair bulb and hair shaft. .. Previously, the dermal papilla area of the hair follicle was thought to be the main control focus of cell regrowth and inhibition [25]. The findings from this study also suggest an important role of the upper-lower portion, infundibular area of the hair shaft where inner and outer root sheath are abruptly changing and that this area may play a role in the regulation of normal hair apoptosis. ….