HAIR SHAFT FORMATION AND MITOCHONDRIAL BIOENERGETICS 329 BIOENERGETICS: MITOCHONDRIA AS A TARGET FOR HAIR BENEFITS Overall, hair follicle metabolism shows high compartmentalization. The DP is relatively quiescent, with little mitochondrial metabolism and low ROS generation. The base of the bulb indicates an area of high mitochondrial membrane potential but low ROS gen- eration, indicative of the proliferative nature or the bulb base. Moving upward past Auber’s line (Figure 3), the cells continue to have high mitochondrial membrane poten- tial but now increasing ROS production and presence of acidic secretory vesicles (53). The “ring of fi re” indicates the highest local region of ROS production and is likely as- sociated with initial keratinization of the IRS. Once passing the “Orwin’s transition,” the mitochondrial membrane potential is lost and there only remains the generation of ROS associated with keratinization and cross-linking. Leverage of real-time imaging of living tissues, in particular growing isolated human hair follicles will provide new insights into hair follicle morphology and bioenergetics and increase our fundamental knowledge of hair growth and metabolism. Better understanding of the mechanisms underlying hair growth may lead to better strategies to treat alopecia and hirsutism, enhance wool pro- duction, and develop new cosmetic products. PHYSICS: THE DEAD HAIR PRODUCT/FUNCTIONAL PHENOTYPE At this point, biology and chemistry have created the basic hair shaft structure. The cur- rent state of cosmetic hair science employs physics and physical chemistry to measure the properties of the hair shaft and relate them to consumer perception and benefi t. Under- standing how the physical measures work and how they quantify properties gives insight into how potential biological changes may contribute to hair physical properties. Figure 3. Loc ation of key compartments of follicle metabolism, biological, and chemical activity in a living human hair follicle.

JOURNAL OF COSMETIC SCIENCE 330 Mature hair is dead hair, composed of the dead remnants of cells that have been sacrifi - cially transformed into the cuticle, cortex, and medulla (63). The function of hair, defi ned by their structure, protein chemistry, and mechanical properties, is codifi ed in life to generate a phenotype that only becomes functional after death. How human hair pheno- type is determined by specifi c genetic controls remains mostly unknown. Most genetic disorders that may provide interesting clues come from human heritable diseases, such as monilethrix mentioned previously, or similar scenarios in animal models. We propose that macroscale studies of hair phenotype should form an essential complement to bio- logically driven hair research (64). SUMMARY AND CONCLUSIONS Generation of human hair is a complex process involving biology to create biomass and generate biosynthetic building blocks and chemistry to use these building blocks to cre- ate the fi nal hair shaft. These activities are compartmentalized within the hair follicle, a complex structure with many cell types coordinated into a single production unit. Mea- surement of the end product, the hair shaft, is mainly based on physics. To best serve patients, hair loss subjects, and consumers in need of better hair, the scientifi c com- munities in the diverse disciplines of biology, chemistry, and physics need to work together. When merged, a joint program has defi ned follicle energy production and mitochondrial energy production as high potential intervention points for designing new products. REFERENCES (1) P. Mohammadi, K. K. Youssef, S. Abbasalizadeh, H. Baharvand, and N. Aghdami, Human hair recon- struction: close, but yet so far, Stem Cells Dev., 25, 1767–1779 (2016). ( 2) C. Robbins, P. Mirmirani, A. G. Messenger, M. P. Birch, R. S. Youngquist, M. Tamura, T. Filloon, F. Luo, and T. L. Dawson Jr., What women want—quantifying the perception of hair amount: an analysis of hair diameter and density changes with age in Caucasian women, Br. J. Dermatol., 167, 324–332 (2012). ( 3) R. Sinclair, M. Patel, T. L. Dawson, A. Yazdabadi, L. Yip, A. Perez, and N. W. Rufaut, Hair loss in women: medical and cosmetic approaches to increase scalp hair fullness, Br. J. Dermatol., 165, 12–18 (2011). ( 4) R. M. Trüeb, Pharmacologic interventions in aging hair, Aging, 1, 121–129 (2006). (5) N. Hunt and S. McHale, The psychological impact of alopecia, Br. Med. J., 331, 951–953 (2005). (6) Statista. The statistics portal. Global hair care market size 2012–2024. Available at: https://www. statista.com/statistics/254608/global-hair-care-market-size. Accessed July 29, 2018. (7 ) J. W. Oh, J. Kloepper, E. A. Langan, Y. Kim, J. Yeo, M. J. Kim, T. C. Hsi, C. Rose, G. S. Yoon, S. J. Lee, J. Seykora, J. C. Kim, Y. K. Sung, M. Kim, R. Paus, and M. V. Plikus, A guide to studying human hair follicle cycling in vivo, J. Invest. Dermatol., 136, 34–44 (2016). (8) M. Saitoh, M. Uzuka, H. Sakamoto, and T. Kobori, “Rate of hair growth,” in Advances in Biology of Skin, W. D. Montagna and R. L. Oxford. Eds. (Pergamon Press, New York, NY, 1969), pp. 183–201. (9) F. J. Ebling and P. J. Hale, “Hormones and hair growth,” in Biochemistry and Physiology of the Skin, L. A. Goldsmith. Ed. (Oxford University Press, New York, NY, 1983), pp. 522–562. (1 0) D. J. Cottle, Australian Sheep, and Wool Handbook (Inkata Press, Melbourne, Australia, 1991). (1 1) J. P. Hogan, N. M. Elliott, and A. D. Hughes, “Maximum wool growth rates expected from Australian merino genotypes,” in Physiological and Environmental Limitations to Wool Growth, J. L. Black and P. J. Reis. Eds. (University of New England, Armidale, New South Wales, Australia, 1979), pp. 43.