Activating Autophagy to Energize Scalp Hair and Eyelash Growth

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Consumer interest in hair growth products continues to rise. The global market was estimated at US $581.5 million in 2022 and is expected to reach $810.1 million by 2028. Products in demand extend beyond those that stimulate regrowth to include products that lessen or forestall loss and thinning. Such demand is driven in part by lifestyles and increased incidences of illnesses that lead to balding over time.1

The quest to develop effective hair loss treatments has been a long one and solutions have met varying levels of success along the way. As such, novel approaches to address this widespread consumer concern are needed. The present article proposes a Cucurbita pepo (pumpkin) var. styriaca extract to supply nutrients and activate follicular autophagy, in turn energizing the growth phase of the hair cycle.

Hair Growth Cycle

For the present discussion, an explanation of the biology would first be helpful. On average, about 90% of hairs on the human scalp are in the growing (anagen) phase, while 5% are in the transition (catagen) phase and 10-15% are in the resting (telogen) phase.2 Dermal papilla cells are responsible for the synchronization and orchestration of cyclical hair growth process. New follicular keratinocytes are supplied from the bulge – a stem cell niche in the region of the arrector pili muscle. The follicular keratinocytes travel via the outer root sheath to the hair bulb where they proliferate, expand and cornify (see Figure 1).

After leaving the basal bulb region, a nascent hair traverses approximately 4 mm to emerge from the scalp surface in a process that takes about two weeks.3 This keratinization/cornification process combines different biological, biochemical and biophysical mechanisms, and it starts above the Auber's Line; i.e., the “line” across the widest portion of the bulb below which cells are undifferentiated.4, 5

The terminal differentiation of follicular keratinocytes consumes significant amounts of energy and requires extensive synchronization and organization. The zone in the hair bulb where this happens is called the ring of fire (see Figure 1). This is the area where the greatest transformation of cells occurs. Eventually all cellular components are broken down, recycled and converted into new building blocks that are used to form hair shafts. Apart from the enormous amount of energy required, the cells also need a reliable recycling system.6-8

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  1. Business Research Insights (2023, Jan). Hair growth treatment product market size, share, growth and industry analysis by type (herb, medicine, nutrition tonic), by application (male-pattern hair loss, female-pattern hair loss) regional forecast to 2028. Available at
  2. Lemasters, J.J., Ramshesh, V.K., ... Dawson, Jr., T.L., et al. (2017). Compartmentation of mitochondrial and oxidative metabolism in growing hair follicles: A ring of fire. J Invest Derm. 137 1434e1444;
  3. Shafayet Zamil, M., Harland, D.P., Fisher, B.K., Davis, M.G., Schwartz, J.R. Geitmann, A. (2021). Biomechanics of hair fiber growth: A multi-scale modeling approach. Journal of the Mechanics and Physics of Solids. 148.
  4. Lim, Y.S., Harland, D.P. and Dawson, T.L., Jr. (2019). Wanted, dead and alive: Why a multidisciplinary approach is needed to unlock hair treatment potential. Exp Dermatol. 28(5) 517-527;
  5. Lippens, S., Denecker, G., Ovaere, P., Vandenabeele, P. and Declercq, W. (2005). Death penalty for keratinocytes: Apoptosis versus cornification. Cell Death Differ. 12 suppl 2 1497-1508;
  6. Kang, J.I., Choi, Y.K., ... Kang, H.K., et al. (2022). 5-Bromo-3,4-dihydroxybenzaldehyde promotes hair growth through activation of Wnt/beta-catenin and autophagy pathways and inhibition of TGF-beta pathways in dermal papilla cells. Molecules. 27(7);
  7. Koenig, U., Robenek, H., ... Hartmann, C., et al. (2020). Cell death induced autophagy contributes to terminal differentiation of skin and skin appendages. Autophagy. 16(5) 932-945;
  8. Parodi, C., Hardman, J.A., ... Grimaldi, B., et al. (2018). Autophagy is essential for maintaining the growth of a human (mini-)organ: Evidence from scalp hair follicle organ culture. PLoS Biol. 16(3) e2002864;
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