​Epidermal cell turnover: Debunking the 28-day myth

The widespread belief that the epidermis renews itself every 28 days is inaccurate. Epidermal turnover primarily involves keratinocytes, the predominant cell type in the epidermis with 90%. These cells originate in the basal layer (stratum germinativum) and progressively move upward through the epidermal layers, undergoing various changes before being shed from the skin's surface as dead, flaky cells - a process known as desquamation [1].

The keratinocyte journey has several stages:

1. 1. Formation in the basal layer
2. 2. Migration through epidermal layers
3. 3. Maturation and differentiation
4. 4. Transformation into corneocytes (fully differentiated keratinocytes without nuclei or organelles)
5. 5. Shedding from the stratum corneum (outermost epidermal layer) [1]

This continuous cycle of cell production, maturation, and shedding is called epidermal turnover [1]
 
Epidermal turnover rates vary significantly with age:
▌In young adults: approximately 28-40 days [2]
▌In more mature adults: 60+ days [2]
This age-related slowdown is attributed to decreased cell proliferation [3]

KERATINOCYTE LIFESPAN 
The keratinocyte lifecycle can be divided into two main phases:
1. Active life: Approximately 8 to 10 days from mitosis (in the basal layer) to arrival in the stratum corneum [1].
2. Stratum corneum transit: The period spent in the outermost layer as corneocytes (dead keratinocytes) before shedding [1].

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Epidermal turnover dynamics
The total epidermal turnover time, which includes both active life and stratum corneum transit, varies with age:
▌In young adults: The stratum corneum transit time is approximately 20 days [3]
▌In more mature adults: This transit time is lengthened by more than 10 days (approximately 30+ days) [3]
This increase in transit time reflects a slowdown in epidermal cell proliferation rather than an increase in cell layers [3]
On average, it takes an estimated 40 to 56 days for the keratinocytes in the epidermis to completely turn over [1]
 
Overall epidermal turnover times
Total turnover time (including both active life and stratum corneum transit) varies significantly with age. The decline in epidermal cell renewal is not constant throughout adulthood, remaining relatively stable in younger years before dropping more dramatically after age 50 [3].

Several factors influence the epidermal turnover of keratinocytes
1. Age: Epidermal turnover slows with age. In young adults, the process takes approximately 28-40 days, while in older adults it can extend to 60+ days [4].
2. Growth factors: Epidermal growth factor (EGF) and keratinocyte growth factor (KGF) play crucial roles in regulating keratinocyte proliferation, migration, and differentiation [5].
3. Transcription factors: p63, particularly the ΔNp63α isoform, is critical for maintaining keratinocyte proliferation and regulating the switch from proliferation to differentiation [4].
4. Signaling pathways: Notch signaling, IKKα, and IRF6 are involved in regulating keratinocyte differentiation and epidermal turnover [4].
5. Matrix stiffness: Increased extracellular matrix stiffness promotes keratinocyte proliferation through enhanced EGF signaling [5].
6. Vitamin D: 1,25-dihydroxyvitamin D3 regulates keratinocyte proliferation and differentiation by modulating calcium concentrations and gene expression [6].
7. Cell adhesion: Contact with the basal lamina, mediated by integrins, regulates keratinocyte proliferation and differentiation [7].
These factors work in concert to maintain the balance between keratinocyte proliferation in the basal layer and terminal differentiation in the upper layers, ensuring proper epidermal homeostasis and turnover.

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Improving epidermal turnover can be beneficial for several skin conditions, including:
1. Aging: Enhanced epidermal turnover can help reduce visible signs of aging such as:
▌ Wrinkles and fine lines
▌ Skin sagging
▌ Dull, rough skin texture (the size or the corneocytes is increased - see graph)
2. Acne: Faster skin cell turnover can help prevent acne by:
▌ Reducing the accumulation of dead skin cells that can clog pores
▌ Decreasing the risk of bacteria buildup on the skin surface
3. Hyperpigmentation and age spots: Improved turnover can address patches of darkened skin by promoting the removal of older, pigment-producing cells
4. Dry skin: Enhanced cell turnover can help improve skin hydration and barrier function [8]
5. Sun damage: Accelerated epidermal renewal can aid in repairing and replacing sun-damaged skin cells [9]

Several in-office procedures and cosmetic ingredients have been shown to accelerate keratinocyte renewal and epidermal turnover:
1. Hyaluronic acid (HA) production enhancers:
▌1-ethyl-β-N-acetylglucosaminide (β-NAG2) has been shown to increase HA production in the epidermis, leading to accelerated keratinocyte proliferation and differentiation [10].
2. Retinoids:
▌Topical retinoids, such as tretinoin, can increase epidermal turnover and promote keratinocyte proliferation [11].
3. Chemical peels:
▌Various chemical peeling agents can stimulate epidermal renewal by inducing controlled damage to the skin [11].
4. Microdermabrasion:
▌This procedure can promote skin turnover by physically removing the outermost layer of dead skin cells [11]
5. Laser treatments:
▌Certain laser therapies can stimulate epidermal regeneration and increase keratinocyte turnover [11]
6. Liquid Crystal Gel (LCG):
▌A study showed that low concentration LCG can increase epidermal thickness and potentially promote skin turnover [11]

Excessive stimulation may lead to adverse effects. Therefore, these treatments should be used under professional guidance and with careful consideration of individual skin conditions. Always consult a qualified healthcare professional to determine what the most suitable approach is for your needs and  goals. 

Take care
Anne-Marie

References:
[1] Iizuka H. Epidermal turnover time. J Dermatol Sci. 1994 Dec;8(3):215-7. doi: 10.1016/0923-1811(94)90057-4. PMID: 7865480.
​[2] Maeda, K. New Method of Measurement of Epidermal Turnover in Humans. Cosmetics 2017, 4, 47. 
[3] Grove GL, Kligman AM. Age-associated changes in human epidermal cell renewal. J Gerontol. 1983;38(2):137-42. doi:10.1093/geronj/38.2.137
[4] Koster MI, Roop DR. J Invest Dermatol. 2007;127(11):2432-8. PMID: 17934504.
[5] Wickert LE, et al. J Cell Sci. 2018;131(10):jcs215780. PMID: 29661845.
[6] Wikipedia contributors. "Keratinocyte." Wikipedia, The Free Encyclopedia. 
[7] Megías M, et al. "Keratinocyte." Atlas of Plant and Animal Histology. University of Vigo. 
[8] Farage MA, Miller KW, Elsner P, Maibach HI. Aging Clin Exp Res. 2008;20(3):195-204. doi:10.1007/BF03020230.
[9] Yaar M, Gilchrest BA. J Investig Dermatol Symp Proc. 2007;12(1):1-10. doi:10.1038/sj.jidsymp.5650020.
[10] Yoshida H, et al. J Dermatol Sci. 2021;101(2):122-131. PMID: 33358097.
[11] Musashi M, et al. Cosmetics. 2014;1(3):202-210. doi:10.3390/cosmetics1030202.