Researchers here investigate declining mitochondrial function in the context of hair growth, suggesting that age-related mitochondrial dysfunction is one of the causes of loss of hair in later life. Lower levels of – and less efficient – mitochondrial activity is implicated in a number of age-related diseases, especially those of the brain, where correct function requires large amounts of the energy store molecules produced by mitochondria. There appear to be several processes at work, ranging from mitochondrial DNA damage thought important in the SENS view of aging to a general and broader mitochondrial malaise that might result from dysfunctional regulation of cellular metabolism, a reaction to other forms of cell and tissue damage.
Emerging research revealed the essential role of mitochondria in regulating stem/progenitor cell differentiation of neural progenitor cells and other stem cells through reactive oxygen species (ROS), Notch or other signaling pathway. Inhibition of mitochondrial protein synthesis results in hair loss upon injury. However, alteration of mitochondrial morphology and metabolic function during hair follicle stem cells (HFSCs) differentiation and how they affect hair regeneration has not been elaborated upon.
Hair follicle (HF) is a cystic tissue surrounding the hair root, controlling hair growth. It consists of two parts: an epithelial part (hair matrix and outer root sheath) and a dermal part (dermal papilla and connective tissue sheath). The hair follicle goes through cycles of anagen phase (growth), catagen phase (degeneration) and telogen phase (rest). In the late telogen phase, hair follicle bulge stem cells differentiate into matrix cells upon stimulation, to re-enter the anagen phase. While in the catagen phase, proliferation and differentiation of hair follicle cells gradually attenuates, leaving with HFSCs and a dormant hair germ, re-entering the telogen phase.
As an essential organelle for anaerobic respiration, mitochondria attracted more research attention to its morphology and function during stem cell differentiation. Mitochondria show less mass in embryonic stem cells (ESCs) than that in differentiated cells, with a reduced oxygen consumption rate and less ROS produced. Effective control of mitochondrial morphology and function is critical for the maintenance of energy production and the prevention of oxidative stress-induced damage resulting from ROS. Besides, mitochondria play an essential role in determining hair cell differentiation and proliferation upon injury though regulating energy metabolism. In addition, ROS inhibit stem cell differentiation and proliferation through redox signaling pathway. Therefore, to counteract the adverse effect of ROS, the level of enzymes such as SOD2 is subsequently up-regulated.
We compared the difference in mitochondrial morphology and activity between telogen bulge cells and anagen matrix cells. Expression levels of mitochondrial ROS and superoxide dismutase 2 (SOD2) were measured to evaluate redox balance. In addition, the level of pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase (PDH) were estimated to present the change in energetic metabolism during differentiation. To explore the effect of the mitochondrial metabolism on regulating hair regeneration, hair growth was observed after application of a mitochondrial respiratory inhibitor upon hair plucking. The results revealed that disrupting mitochondrial respiration delays hair regrowth. It is possible that hair regeneration might be retarded due to insufficient energy supply. Another possibility is that mitochondrial dysfunction affects HFSCs differentiation through regulating redox balance or other signaling pathways, leading to the delay of hair growth.