Dermal damage promoted by repeated low-level UV-A1 exposure despite tanning response in human skin

Abstract

Importance: Solar UV irradiation causes photoaging, characterized by fragmentation and reduced production of type I collagen fibrils that provide strength to skin. Exposure to UV-B irradiation (280-320 nm) causes these changes by inducing matrix metalloproteinase 1 and suppressing type I collagen synthesis. The role of UV-A irradiation (320-400 nm) in promoting similar molecular alterations is less clear yet important to consider because it is 10 to 100 times more abundant in natural sunlight than UV-B irradiation and penetrates deeper into the dermis than UV-B irradiation. Most (approximately 75%) of solar UV-A irradiation is composed of UV-A1 irradiation (340-400 nm), which is also the primary component of tanning beds.

Objective: To evaluate the effects of low levels of UV-A1 irradiation, as might be encountered in daily life, on expression of matrix metalloproteinase 1 and type I procollagen (the precursor of type I collagen).

Design, setting, and participants: In vivo biochemical analyses were conducted after UV-A1 irradiation of normal human skin at an academic referral center. Participants included 22 healthy individuals without skin disease.

Main outcomes and measures: Skin pigmentation was measured by a color meter (chromometer) under the L* variable (luminescence), which ranges from 0 (black) to 100 (white). Gene expression in skin samples was assessed by real-time polymerase chain reaction.

Results: Lightly pigmented human skin (L* >65) was exposed up to 4 times (1 exposure/d) to UV-A1 irradiation at a low dose (20 J/cm2), mimicking UV-A levels from strong sun exposure lasting approximately 2 hours. A single exposure to low-dose UV-A1 irradiation darkened skin slightly and did not alter matrix metalloproteinase 1 or type I procollagen gene expression. With repeated low-dose UV-A1 irradiation, skin darkened incrementally with each exposure. Despite this darkening, 2 or more exposures to low-dose UV-A1 irradiation significantly induced matrix metalloproteinase 1 gene expression, which increased progressively with successive exposures. Repeated UV-A1 exposures did not suppress type I procollagen expression.

Conclusions and relevance: A limited number of low-dose UV-A1 exposures, as commonly experienced in daily life, potentially promotes photoaging by affecting breakdown, rather than synthesis, of collagen. Progressive skin darkening in response to repeated low-dose UV-A1 exposures in lightly pigmented individuals does not prevent UV-A1-induced collagenolytic changes. Therefore, for optimal protection against skin damage, sunscreen formulations should filter all UV wavelengths, including UV-A1 irradiation.

Figure 1. Exposure of lightly pigmented human skin to UVA1 irradiation causes skin darkening, induction of matrix metalloproteinases, and suppression of procollagens in a dose-dependent fashion

Skin pigmentation was measured using a color meter (chromameter) under the L* variable (luminescence), which ranges from 0 (black) to 100 (white). Lightly pigmented (L*>65) buttock skin of healthy human subjects (n=10) was exposed to the indicated doses of UVA1 irradiation. (a) Changes in skin pigmentation were measured 24 hours later (L* value, n=10). (b) Additionally, skin samples (4 mm) were obtained 24 hours following exposure, and real-time polymerase chain reaction was performed to assess gene expression of matrix metalloproteinase (MMP)-1, MMP-3, type I procollagen (COL-I), and type III procollagen (COL-III) (all n=10). The housekeeping gene acidic ribosomal phosphoprotein P0 (36B4) was used as an internal control. Data are presented as mean fold change + SEM. Asterisk (*) over bars, p<0.05 compared with no UVA1 irradiation. Asterisk (*) over bracket, p<0.05 when comparing response to different UVA1 doses.

Figure 2. Repeated daily exposure of lightly pigmented human skin to low-dose UVA1 irradiation causes incremental darkening and progressive induction of matrix metalloproteinases

Skin pigmentation was measured using a color meter (chromameter) under the L* variable (luminescence). Lightly pigmented (L*>65) buttock skin of healthy human subjects (n=12) was exposed to low-dose UVA1 irradiation (20 J/cm²) one, two, three, or four times at daily intervals. (a) Changes in skin pigmentation were measured 24 hours after each exposure (L* value, n=12). (b) Skin samples (4 mm) were also obtained 24 hours following each exposure, and real-time polymerase chain reaction was performed to assess gene expression of matrix metalloproteinase (MMP)-1, MMP-3, type I procollagen (COL-I), and type III procollagen (COL-III) (all n=12). The housekeeping gene acidic ribosomal phosphoprotein P0 (36B4) was used as an internal control. Data are presented as mean fold change + SEM. Asterisk (*) over bars, p<0.05 compared with no UVA1 irradiation. Asterisk (*) over bracket, p<0.05 when comparing response to different UVA1 exposures.