Fat infiltration into dermal layer induces aged facial appearance by decreasing dermal elasticity

Abstract

Background

Facial morphology changes with aging, producing an aged appearance, but the mechanisms involved are not fully established. We recently showed that subcutaneous fat infiltrates into the dermal layer with aging, but it is not yet clear whether and how this drastic change of the dermal layer influences facial appearance.

Purpose

We aimed to establish the role of fat infiltration in producing an aged facial appearance and to clarify the mechanism involved.

Methods

We analyzed the severity of fat infiltration in cheek skin of 30 middle‐aged female volunteers by means of ultrasonography. Severity of the nasolabial fold, an established age‐related morphology, was evaluated based on our photographic grading criteria as a measure of aged appearance. Skin elasticity was measured with a Cutometer.

Results

Fat infiltration to the dermal layer was detected at the cheek skin noninvasively by means of ultrasonography. Fat infiltration severity, measured as the minimum depth of the fat inside the dermal layer from the skin surface, was positively correlated with the magnitude of the nasolabial fold. Further, fat infiltration severity was significantly negatively correlated with dermal elasticity.

Conclusions

Our results suggest that fat infiltration into the dermal layer is a critical factor inducing aged appearance of the face. The infiltrated fat decreases the dermal elasticity, which exacerbates nasolabial folds, namely producing an aged facial appearance.

1. INTRODUCTION

Facial morphology changes drastically with aging, ¹ , ² in both women and men, ³ and many studies have been conducted to clarify the mechanisms involved from the viewpoints of cosmetics development, ⁴ dermatology, ⁵ plastic surgery, ⁶ pharmacology, ⁷ and so on. We have reported that dermal elasticity is important for the maintenance of facial morphology, and loss of elasticity exacerbates various features of aged appearance. ⁸ Dermal elasticity is mainly a property of the dermal layer, which contains abundant extracellular matrix molecules (ECMs), such as collagen and elastic fibers. ⁹ Thus, age‐dependent changes in the quality of dermal ECMs have widely been studied, including the deterioration of collagen fibers ¹⁰ and accumulation of abnormal elastic fibers in photo‐exposed skin, or solar elastosis. ¹¹ However, structural changes of the dermal layer have been little explored, probably because the structure of the dermal layer is too complicated to analyze by means of conventional two‐dimensional (2D) histological observation, due to the great variety of internal appendages, such as sweat glands, fair follicles, sebaceous glands, and so on.

We recently developed a 3D analysis method for skin based on X‐ray micro CT observation followed by digital reconstruction on computer, which makes it possible to observe and quantify complex internal structures of skin on computer. ¹² By means of this technology, we clarified that subcutaneous fat infiltrates into the dermal layer with aging in abdominal skin. ¹³ The resulting loss of extracellular matrix of the dermal layer could impair the skin elasticity, and negatively influence body surface morphology, producing an aged appearance. However, it is not clear whether this fat infiltration also occurs in facial skin, and its impact on the dermal properties and its role in facial aging remain to be established.

Nasolabial folds are deep folds formed from the side of the nose to the corners of the mouth and are key features of aged appearance. We have reported that nasolabial fold formation with aging is associated with decreased dermal elasticity. ¹⁴

The aim of this study was to examine the role of fat infiltration into the dermis in producing an aged facial appearance and also to clarify the mechanism involved. For this purpose, we studied whether fat infiltration influences the formation of nasolabial folds, which are considered to be representative of the age‐dependent changes of facial morphology. We further investigated the relationship between fat infiltration and dermal elasticity.

2. METHODS

2.1. Subjects

Thirty healthy Japanese middle‐aged female volunteers (age range: 30s–50s) participated in this research with the approval of Shiseido's ethics committee. Subjects had a body mass index of less than 25, which is in the normal range according to the WHO obesity classification. Participants were not smokers and were not taking medicines. There were no drop‐outs during the study.

2.2. Study protocol

Subjects were allowed to acclimate to the standard environmental conditions after they had washed their face. Then, photographs of the face were taken from sagittal direction at an angle of 45 degrees, under constant lighting conditions. Skin condition was measured with a cutometer and by ultrasonography as described below. Nasolabial fold (Figure 1A) severity was evaluated according to our previously reported photograph‐based 6‐grade classification. ¹⁴

FIGURE 1.

Nasolabial fold and fat infiltration (A) Upper cheek area. The nasolabial fold is indicated by a dotted line. Nasolabial fold severity was evaluated according to our photograph‐based grading criteria. (B) Fat infiltration into the dermal layer, observed by ultrasonography. The minimum depth of the fat from the skin surface was measured as the indicator of the degree of fat infiltration (fat infiltration index).

2.3. Measurement of dermal elasticity

Dermal elasticity was measured noninvasively with a Cutometer MPA 580 (Courage & Khazaka, Cologne, Germany) at the center of the upper cheek, as described previously. ¹⁵ , ¹⁶ , ¹⁷ Briefly, skin was suctioned for a period of 2 s, followed by a 2‐s relaxation time. Then elastic parameters, such as Ue (immediate distension of the skin, representing elastic deformation), Ur (immediate retraction of the skin, representing the elastic deformation recovery), Uf (final distension at the end of the vacuum period, representing the total extensibility of the skin), and Ua (total deformation recovery) were obtained from the skin deformation curves (Figure 3A). The values of Ur/Ue (net elasticity without viscoelastic creep) and the Ua/Uf (overall elasticity including creep and creep recovery) were calculated from these parameters.

FIGURE 3.

Fat infiltration decreases dermal elasticity. Dermal elasticity was measured with a Cutometer MPA 580. (A) Parameters measured with the cutometer during skin suction (time: 0) and release (time: 2.0 sec) by monitoring the displacement amount of the skin surface. (B and C) Relationship between fat infiltration index to dermal elasticity parameters. Note a lower value of fat infiltration index represents a greater degree of infiltration (see Figure 1). Statistical analysis was carried out using Pearson's correlation coefficient (N = 30, middle‐aged female volunteers). Note: A lower value of fat infiltration index corresponds to more severe fat infiltration.

2.4. Measurement of fat infiltration

The extent of fat infiltration was measured noninvasively by means of ultrasonography at the same area measured by the cutometer. We used a Prosound alpha 5 13 MHz probe (Aloka Co., Ltd., Tokyo, Japan) with ultrasound gel, as previously described. ¹⁸ We swept the ultrasonography probe to confirm that fat in the dermal layer was connected to the subcutaneous adipose layer and did not simply represent isolated defects in the dermal layer. We measured the minimum distance (depth) of subcutaneous fat in the dermal layer from the skin surface as an index of the degree of fat infiltration.

2.5. Statistical analysis

Correlations were evaluated in terms of Pearson's correlation coefficient or Spearman's correlation coefficient. A p‐value of less than 0.05 was considered significant.

3. RESULTS

3.1. Fat infiltration into the dermal layer at the upper cheek

Ultrasonography revealed the presence of fat in the dermal layer at the upper cheek, showing the same intensity as the subcutaneous adipose layer (Figure 1B). All of these fat infiltrations in the dermal layer were confirmed to be connected to the subcutaneous adipose layer by sweeping the ultrasonography probe. Next, we aimed to evaluate the extent of this fat infiltration. It is still controversial whether an age‐dependent change of the thickness of the dermal layer occurs, ¹⁹ and in any case, the boundary between the dermal layer and subcutaneous fat is uneven (Figure 1B). Here, we found that the value of this fat infiltration index observed in 30 female cheeks showed a Gaussian distribution over the range from 2.10 mm (least infiltrated) to 1.20 mm (most infiltrated), with a mean and standard error (SEM) of 1.65 ± 0.05.

3.2. Fat infiltration increases the severity of nasolabial folds

Next, we analyzed the relationship between the fat infiltration index and nasolabial fold severity. Nasolabial fold severity in our subjects ranged from grade 1 (slight) to grade 5 (severe), with a mean and SEM of 3.4 ± 0.2. The fat infiltration index was inversely correlated with the nasolabial fold severity (Figure 2); in other words, a greater degree of fat infiltration into the dermis was associated with more severe nasolabial folds.

FIGURE 2.

Increment of fat infiltration into the dermal layer increases nasolabial fold severity plot of fat infiltration index against nasolabial fold severity. Note a lower value of fat infiltration index represents a greater degree of infiltration (see Figure 1). Statistical analysis was carried out using Spearman's rank correlation test (N = 30, middle‐aged female volunteers). Note: A lower value of fat infiltration index corresponds to more severe fat infiltration.

3.3. Fat infiltration decreases dermal elasticity

To clarify the mechanism through which fat infiltration might worsen nasolabial folds, we examined the influence of fat infiltration on dermal elasticity. The fat infiltration index was positively correlated to dermal elastic parameters such as Ur/Ue (net elasticity without viscoelastic creep) and the Ua/Uf (overall elasticity including creep and creep recovery) (Figure 3). In other words, increased fat infiltration (lower value of fat infiltration index) is associated with decreased dermal elasticity and viscosity, which exacerbates nasolabial folds, as we have reported before. Thus, increasing fat infiltration into the dermal layer leads to a decrease of dermal elasticity and viscosity, which in turn increases the severity of nasolabial folds.

4. DISCUSSION

In this study, we investigated the mechanism through which fat infiltration into the dermal layer ¹³ influences facial appearance. We found that the extent of fat infiltration was positively correlated with the severity of nasolabial folds, a key contributor to aged facial appearance. We also found that increased fat infiltration is associated with decreased dermal elasticity. These results suggest that fat infiltration causes a reduction of dermal elasticity, which serves to worsen the nasolabial folds.

We previously reported that defects in the dermal layer of abdominal skin appear with aging, ²⁰ and this is due to the infiltration of fat from the subcutaneous adipose layer. ¹³ Here, we established that infiltration of fat into the dermal layer also occurs in cheek skin by means of ultrasonography. We also examined the relationship between fat infiltration severity and the skin viscosity and elasticity by measuring the parameters Ur/Ue and Ua/Uf. The changes of these parameters suggest that fat infiltration may adversely affect the properties of elastic fibers and viscosity‐related molecules such as glycosaminoglycans. ²¹ In other words, fat infiltration into the dermal layer appears to result in a decrease of ECMs, such as collagen and elastic fibers, which contributes to the viscoelasticity properties of the dermal layer, thus leading to a reduction of the dermal elasticity. Further, collagen and elastic fibers are thick at the bottom of the dermal layer, so that fat infiltration at this location would have a particular impact.

We have reported that subcutaneous fat influences dermal condition by secreting a variety of factors that both positively or negatively regulate the condition of ECMs in the dermal layer. ¹⁸ For example, matrix metalloproteinase 9 (MMP9) degrades elastic fibers in the dermal layer, ²² while palmitic acid decreases the expression of collagen and elastin and increases MMP1, which degrades collagen. ²³ Thus, we consider that that the infiltrated fat itself impairs dermal elasticity due to its negative influence on surrounding dermal ECMs, in addition to the direct loss of dermal ECMs due to the fat infiltration. Further study will be needed to confirm this.

Since the loss of dermal elasticity is a critical cause of aged appearance, such as sagging and wrinkling, fat infiltration could contribute to the appearance of a variety of aged facial morphologies. Indeed, in this study we clarified that fat infiltration significantly exacerbates nasolabial folds.

In conclusion, our results show that subcutaneous fat infiltrates into the dermal layer, leading to decreased dermal elasticity and increased severity of the nasolabial folds, a representative feature of aged appearance. Thus, fat infiltration could be a critical target to improve aged facial appearance, as well as age‐related loss of dermal elasticity, which is associated with clinical issues such as pressure ulcer and delayed wound healing. ²⁴

Ezure T, Amano S, Matsuzaki K. Fat infiltration into dermal layer induces aged facial appearance by decreasing dermal elasticity. Skin Res Technol. 2022;28:872–876. 10.1111/srt.13230

DATA AVAILABILITY STATEMENT

Research data are not shared.