J. Cosmet. Sci., 69, 323–333 (September/October 2018) 323 Hair Shaft Formation and Mitochondrial Bioenergetics: Combining Biology, Chemistry, and Physics YI SHAN LIM, DUANE P. HARLAND, and THOMAS L. DAWSON JR., Skin Research Institute of Singapore, Singapore 138648, Singapore (Y.S.L., T.L.D.), AgResearch, Crown Research Institute, Lincoln 7674, New Zealand (D.P.H.), Department of Drug Discovery, Medical University of South Carolina, Charleston, South Carolina (T.L.D.) Synopsis Research into biological manipulation of hair “quality” has ebbed and waned but today is in a resurgence. Hair appearance is regulated by multiple intervention opportunities—adding more hairs increasing hair “amount” by modulating shaft diameter or shape or, in principle, by altering shaft physical properties by changing its synthesis. It is likely that improved benefi ts may be achieved by combining multiple areas— minimizing follicle loss and miniaturization, maximizing shaft production, and treating the existing shaft. A previously overlooked opportunity is follicle metabolism: building “better” hairs. Hair production is energy intensive, and it is known that follicle metabolism infl uences shaft diameter. Multiphoton microscopy enables metabolic investigation of live, growing, human, hair follicles. This allows defi nition of multiple “zones” with vastly different metabolism: proliferation—where keratinocytes proliferate and migrate into specialized layers production—proliferation ceases, and synthesis and patterning begin construction and elongation—the structural framework is seeded and cells extend to create the nascent fi ber and maturation—gradual hardening and transformation into mature shaft. Recent investigations into the transition from construction to maturation reinforce this as a key developmental threshold, where shaft production transforms from a biologically driven into a biochemically driven process. We now name this “Orwin’s transition.” INTRODUCTION Although in general mammalian hair has many useful functions, in humans, terminal scalp hair remains of unknown evolutionary utility. It is almost certainly less about phys- ical functions such as temperature regulation and protection and has become primarily important aesthetically and sexually, very likely an essential part of mate selection. In both men and women, scalp hair is a key perceptual indicator of age, health, and beauty (1–4). Inadequate hair condition and loss of scalp hair clearly has adverse psychological Address all correspondence to Thomas L. Dawson at thomas.dawson@imb.a-star.edu.sg. Yi S. Lim and Duane Harland contributed equally to this work.

JOURNAL OF COSMETIC SCIENCE 324 impact, resulting in signifi cant anxiety and distress (1,5). This is the basis for the estimated $100 billion dollar plus per year demand for treatments that effectively promise to im- prove hair growth and appearance (6). Despite the controversy and lack of clear biological data on why humans have terminal scalp hair, we certainly dedicate a vast amount of energy into its production. Produc- tion of hair depends on adequate regulation of the follicle growth cycle (7) and main- tenance of a well-functioning factory synthesizing hair shaft. If one considers that human scalp hair grows at approximately 0.3 mm/day/follicle and one assumes a total of 100,000 terminal scalp hairs, we produce approximately 2 m of hair shaft per day (8,9). It is diffi cult to defi ne the exact energy required to produce this much hair, but if we consider the human scalp hair as being relatively similar to wool, some data exist. There are many studies that examine sheep diet in respect to wool properties (10,11). A direct application of sheep diet data to humans might not be appropriate because sheep are herbivores, relying on bacterial fermentation in digestion however, the en- ergy required to produce a set weight of hair fi ber is probably similar. In sheep, about 630 kJ of metabolizable energy is required to produce 1 g of clean dry wool (containing 24 kJ gross energy) and 0.27 g wool grease (sheep sebum, containing 11 kJ gross energy). This may seem like a lot of energy it is equivalent to about 10 min of hard exercise with both arms and legs (12) or 400 shots from a Smith and Wesson Model 29 revolver (13) of “Dirty Harry” fame. It is also a lot of hair, with a single ~4-cm human hair weighing in at 0.62 mg. Hence, 1 g of human hair represents about 1,500 hairs of 4 cm in length. Although a rough estimate, this demonstrates the energy intensity of human anagen fol- licles. For example, human scalp hair grows on average 10 mm/month with an estimate of 17–170 vertical cell divisions per cell type (e.g., cortex, cuticle, and Huxley’s layer) per day (14). Although this is almost certainly imprecise (having been derived from various data sources), it highlights the point that a growing hair implies a population of cells at their most active, continually dividing and rapidly differentiating. Mammalian mito- chondria have for many years been a well-researched target for drug therapy, particularly focusing on inhibiting tumor growth via inhibition of mitochondrial metabolism and as a generator of toxic reactive oxygen species after radiation exposure. Thus, there is a wealth of information available to investigate targeting of mitochondrial metabolism in hair loss prevention, and the new techniques reviewed herein should enable more detailed assessment. An optimal head of hair requires adequate follicle density to produce enough visible hair shafts, and each shaft must be functional for coverage and style (2,3). In addition, each hair must be robust enough with strength and durability to sustain years of both delib- erate and unintentional physical and environmental damage. Unfortunately, research into the biology of hair and the physical/chemical properties lie in separate realms: fol- licle regulation and the biological basis of hair production lies in biology and medicine physical/cosmetic properties of the mature hair shaft fall under physics and physical chemistry whereas construction and assembly of the hair shaft are considered oxidative or biochemistry. Hence, subjects (or patients) have suffered because communication between research centers and coordinated treatments from each of the singular afore- mentioned domains has lagged. In order for the best possible outcomes for hair loss, the scientifi c community must implement collaborative programs containing biology, chem- istry, and physics.