Sweat Glands as a Novel Target for Anti-aging Skin Care

During aging, facial appearance changes dramatically. The cheeks descend, nasolabial folds appear, facial contours become less defined and deep, permanent wrinkles develop and more.¹ Although these morphological changes are indicated globally as top concerns among individuals middle-aged and older, the mechanisms involved are largely unknown.

Previously, it has been established that a critical cause of these aging-related changes is the loss of dermal elasticity.² However, to understand the mechanisms of facial aging in greater detail, the changes of intact internal skin structures with aging must be observed. This is a significant challenge because there are many appendages, such as sebaceous glands, sweat glands, hair follicles, blood vessels and so on, in the skin, and few methods are available to observe them.

Sweat Gland Functions and Changes with Age 

Take sweat glands for example. These appendages secrete sweat onto the skin surface and they are composed of two parts (see Figure 1). One is the secretory coil, a coiled structure that creates sweat from blood.³ This primary sweat is delivered to the skin as final sweat after the resorption of NaCl through the secretory duct – the other part of the sweat gland.

There are three types of sweat glands in humans: eccrine, apoeccrine and apocrine.⁴ The major type is the eccrine sweat gland, of which 2-4 million are distributed throughout the skin. Apoeccrine sweat glands are distributed in the axilla, whereas apocrine sweat glands are distributed in the axilla, breasts and perineum.

Although it can be considered a nuisance in daily life, sweating is critical for human beings to cool body temperature via the loss of heat during evaporation. Furthermore, it contributes to moisturizing the skin's surface by supplying water and natural moisturizer components (urea and lactate) to prevent skin dryness.⁵ In addition, sweat forms an acidic mantle on the skin surface, which contributes to the control of commensal organisms on the skin.⁶

However, the sweating function deteriorates with aging, which results in decreased heat tolerance;⁷ little is known about the structural change of sweat glands with aging, since the 3D morphology of the sweat gland is very complex.

Visualizing Internal Structures in Skin

To clarify age-dependent changes of facial skin’s internal structures including sweat glands, among others, a visualization technology was established using X-ray micro-computed tomography^a to observe the structures at a high resolution (at the μm level)⁸ under the following conditions: voltage 80 kV, current 100 microA, rotation 360 degrees, integration time 200 msec. These structures were identified and classified by means of an artificial intelligence (AI) machine-learning system^b that reconstructs the complete 3D skin structure digitally^c. Since this is digitally reconstructed skin, it can be monitored freely; for example, by cutting it or sorting specific targets and manipulating and analyzing them on the computer.

Dermal Cavitation

This digital 3D technology was used to observe young and aged skin. Compared with young skin, old skin had many large defects at the bottom of the dermal layer (see Figure 2).⁸ The defects were filled with fat cells from the subcutaneous adipose layer.⁹ By digitally cutting the skin at a 1 mm depth, approximately 20 defects/cm² in this horizontal skin section were observed.

These defects were all connected to the subcutaneous adipose layer, suggesting they progress from the subcutaneous adipose layer side but not from the internal dermal layer side to the subcutaneous adipose layer. This defect of the dermal layer was designated as dermal cavitation.

Dermal Cavitation, Skin Elasticity and Sagging

Dermal cavitation was found to progress at the bottom of the dermal layer, i.e., the lower part of the reticular dermal layer, which is filled with thicker collagen and elastic fibers (the extracellular matrix or ECM) – the key contributors to skin elasticity – than the upper dermal layer, i.e., the upper part of the reticular dermal layer and papillary dermal layer. Therefore, it was expected that dermal cavitation would influence the skin’s physical properties.

Indeed, skin elasticity measured in the cheeks of middle-aged females significantly decreased with increments of dermal cavitation.¹⁰ Furthermore, dermal cavitation was positively correlated with sagging severity. Therefore, it was considered that dermal cavitation causes a loss of ECM at the bottom of the dermal layer, which decreases dermal elasticity, leading to sagging.

Sweat Glands and Dermal Cavitation

To clarify the mechanism of dermal cavitation, the cavitation area was examined using the described digital 3D technology. This revealed that sweat glands existed at the cavitation sites with high probability in aged skin (see Figure 3). Furthermore, sweat glands were located at the bottom of the dermal layer in young skin, but in aged skin they move upward, toward the skin surface (see Figure 4); though there was no significant change in their size or number with aging.¹¹

Since the bottom of the sweat gland is in contact with the subcutaneous adipose layer,¹² it is proposed that the upward movement of the sweat gland could induce the upward movement of the subcutaneous fat to maintain the contact between the sweat gland coil and subcutaneous adipose layer, thereby inducing dermal cavitation.

The Sweat Gland: An Emerging Anti-aging Target

The novel digital technology described for the 3D visualization of internal skin thus uncovered a previously unknown causal factor of facial aging. Namely, the age-dependent shrinking of sweat glands – which causes them to move upward toward the skin surface, concomitantly inducing an upward movement of the subcutaneous adipose layer just beneath the sweat gland – and thereby causing dermal cavitation (see Figure 5). These large and frequent defects at the bottom of the dermal layer result in the deterioration of dermal elasticity, which in turn promotes sagging.

Nowadays, with lifestyle changes and the progress of technology such as air conditioning, humans tend not to sweat in daily life, which could lead to impaired sweat gland functioning. However, this function can be improved by sweat-induced stimulation such as heating and exercising. Thus, cosmetic approaches including devices, active ingredients, massage and other cosmetic materials could be used to promote sweat gland function. Therefore, the sweat gland could be considered a novel target for anti-aging skin care.

References

1. Ezure, T. and Amano, S. (2012). Involvement of upper cheek sagging in nasolabial fold formation. Skin Res Technol. 18(3) 259-264.
2. Ezure, T., Hoshoi, J., Amano, S. and Tsuchiya, T. (2009). Sagging of the cheek is related to skin elasticity, fat mass and mimetic muscle function. Skin Res Technol. 15 299-305.
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6. Murota, H., Yamaga, K., Ono, E., Murayama, N., Yokozeki, H. and Katayama, I. (2019). Why does sweat lead to the development of itch in atopic dermatitis? Exp Dermatol. 28(12) 1416-1421.
7. Inoue, Y., Nakao, M., Araki, T. and Murakami, H. (1985). Regional differences in the sweating responses of older and younger men. J Appl Physiol. 71(6) 2453-2459.
8. Ezure, T., Amano, S. and Matsuzaki, K. The sweat gland as a breakthrough target for anti-aging skin care discovery of a novel skin aging mechanism, dermal cavitation. IFSCC magazine. 21 3-6.
9. Ezure, T., Amano, S. and Matsuzaki, K. (2022). Infiltration of subcutaneous adipose layer into the dermal layer with aging. Skin Res Technol. 28(2) 311-316.
10. Ezure, T., Amano, S. and Matsuzaki, K. (2022). Fat infiltration into dermal layer induces aged facial appearance by decreasing dermal elasticity. Skin Res Technol. 28(6) 872-876.
11. Ezure, T., Amano, S. and Matsuzaki, K. (2021). Aging-related shift of eccrine sweat glands toward the skin surface due to tangling and rotation of the secretory ducts revealed by digital 3D skin reconstruction. Skin Res Technol. 27(4) 569-575.
12. Bovell, D.L. (2018). The evolution of eccrine sweat gland research toward developing a model for human sweat gland function. Exp Dermatol. 27(5) 544-550

Figure 5. Effect of sweat gland shrinking on cavitation and skin sagging
Figure 4. Sweat gland location in young versus old skinFigure 3. Sweat gland at cavitation siteFigure 2. Dermal cavitationFigure 1. Sweat gland structure