ArticlePDF AvailableLiterature Review

Effects of Infrared Radiation and Heat on Human Skin Aging in vivo

Authors:

Abstract

Sunlight damages human skin, resulting in a wrinkled appearance. Since natural sunlight is polychromatic, its ultimate effects on the human skin are the result of not only the action of each wavelength separately, but also interactions among the many wavelengths, including UV, visible light, and infrared (IR). In direct sunlight, the temperature of human skin rises to about 40 degrees C following the conversion of absorbed IR into heat. So far, our knowledge of the effects of IR radiation or heat on skin aging is limited. Recent work demonstrates that IR and heat exposure each induces cutaneous angiogenesis and inflammatory cellular infiltration, disrupts the dermal extracellular matrix by inducing matrix metalloproteinases, and alters dermal structural proteins, thereby adding to premature skin aging. This review provides a summary of current research on the effects of IR radiation and heat on aging in human skin in vivo.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 15-19; doi:10.1038/jidsymp.2009.7.
Effects of Infrared Radiation and Heat on Human Skin
Aging in vivo
Soyun Cho
1,2,3
, Mi Hee Shin
1,2,3
, Yeon Kyung Kim
1,2,3
, Jo-Eun Seo
1,2,3
, Young Mee Lee
1,2,3
,
Chi-Hyun Park
1,2,3
and Jin Ho Chung
1,2,3
Sunlight damages human skin, resulting in a wrinkled
appearance. Since natural sunlight is polychromatic,
its ultimate effects on the human skin are the result of
not only the action of each wavelength separately, but
also interactions among the many wavelengths,
including UV, visible light, and infrared (IR). In direct
sunlight, the temperature of human skin rises to
about 401C following the conversion of absorbed IR
into heat. So far, our knowledge of the effects of IR
radiation or heat on skin aging is limited. Recent work
demonstrates that IR and heat exposure each induces
cutaneous angiogenesis and inflammatory cellular
infiltration, disrupts the dermal extracellular matrix
by inducing matrix metalloproteinases, and alters
dermal structural proteins, thereby adding to pre-
mature skin aging. This review provides a summary of
current research on the effects of IR radiation and
heat on aging in human skin
in vivo
.
Journal of Investigative Dermatology Symposium Proceedings (2009) 14,
15–19; doi:10.1038/jidsymp.2009.7
INTRODUCTION
Infrared (IR) radiation consists of wavelengths from 760 nm to
1 mm, and it is subdivided into three regions of increasing
wavelength, IR-A (760–1400 nm), IR-B (1400–3000 nm), and
IR-C (3000 nm–1 mm). Given that almost half of the solar
energy reaching the earth’s surface is in the IR range, solar IR
is expected to have significant biological effects on human
skin.
Heat is a form of energy that may be transmitted by IR
radiation, which results in raised skin temperature. Human
skin is exposed daily to natural sunlight. We found that the
temperature of human skin can increase to more than 401C
under direct IR irradiation (Lee et al., 2006) due to the
conversion of IR into heat. There is clinical evidence
indicating that chronic heat exposure of human skin may
cause alterations. The skin disease called erythema ab igne is
known to be caused by chronic heat exposure. It is
characterized clinically by reticular pigmentation of the skin
and histologically by the presence of solar elastosis in the
dermis similar to what is seen in photoaged skin. Further-
more, severe skin aging may develop occasionally on bakers’
arms, because of exposure to hot ovens, and on the faces of
glass blowers.
However, the effects of IR radiation and heat on cutaneous
aging are still largely unknown. This review provides an
overview of the current knowledge of contributions of IR
radiation and heat exposure to aging in human skin.
EFFECTS OF IR RADIATION ON AGING IN HUMAN SKIN
IN VIVO
It has been reported that IR-A can penetrate epidermal and
dermal layers and reach subcutaneous tissues without
increasing the skin temperature significantly, whereas IR-B
and IR-C are absorbed mostly in the epidermal layers and
increase skin temperature significantly (Schieke et al., 2003).
The few studies conducted on IR collectively have concluded
that IR radiation produces heat upon exposure. Considering
the general principle that all biochemical processes are
affected by temperature, the effects of IR on human skin can
no longer be ignored.
Effects of IR on the expression of collagen and MMPs in human
skin in vivo
Alterations and deficiencies of collagen, the major structural
component of the skin, have been suggested to be a cause of
the skin wrinkling observed in both photoaged and naturally
aged skin (Fisher et al., 1997; Varani et al., 2000). Because
collagen fibrils are responsible for the strength and resilience
of skin, their disarrangement during photoaging causes the
skin to appear aged. Excessive matrix degradation by UV-
induced matrix metalloproteinases (MMPs) secreted by
various cells, including keratinocytes, fibroblasts, and in-
flammatory cells, contributes substantially to the connective
tissue damage that occurs during photoaging (Fisher et al.,
1996; Chung et al., 2001, 2002). Although human skin is
frequently exposed to IR radiation, little is known about the
&2009 The Society for Investigative Dermatology www.jidonline.org 15
REVIEW
Received 14 November 2008; accepted 8 January 2009
1
Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea;
2
Laboratory of Cutaneous Aging Research, Clinical Research
Institute, Seoul National University Hospital, Seoul, Korea and
3
Institute of Dermatological Science, Seoul National University, Seoul, Korea
Correspondence: Dr Jin Ho Chung, Department of Dermatology, Seoul National University Hospital, 28 Yongon-dong, Chongno-Gu, Seoul 110-744, Korea.
E-mail: jhchung@snu.ac.kr
Abbreviations: IR, infrared; MMP, matrix metalloproteinase; ROS, reactive oxygen species; TRPV, transient receptor potential vanilloid
biological effects of IR on collagen metabolism. We reported
the effects of acute and chronic IR exposure on type I
procollagen expression (Kim et al., 2006b). To investigate the
effects of IR irradiation, we exposed human buttock skin to
near-IR radiation. Previously, we had proposed the minimal
heating dose as a standard unit to measure IR energy incident
on human skin (Lee et al., 2006). When we irradiated
volunteers’ skin with IR, skin temperature rose to a certain
point and then plateaued. We defined this radiation
dose where the skin temperature plateaued as the minimal
heating dose. Three minimal heating doses were irradiated
on human buttock skin once or three times a week for 4
weeks. It was found that although single IR irradiation
increased type I procollagen expression, multiple irradiations
reduced its expression (Kim et al., 2006b). Single IR
irradiation increased the expression of TGF-b1, -b2, and
-b3 in human skin in vivo, whereas repeated IR irradiation
reduced the expression of these TGF-bs. It is well known that
TGF-bpotently stimulates the proliferation of fibroblasts in
the dermis and induces the synthesis and secretion of
procollagen (Massague, 1998). Therefore, alterations in
TGF-bmay have influenced type I procollagen expression
in IR-exposed human skin.
It was reported that a single treatment of human
dermal fibroblasts with IR-A-induced MMP-1 (Schieke
et al., 2002). However, we demonstrated that MMP-1 was
not induced by single IR irradiation in human skin in vivo
(Kim et al., 2006b). In contrast to the effects of a single IR
irradiation, multiple IR irradiations significantly increased
MMP-1 expression. Therefore, repeated IR exposure might
induce premature skin aging (photoaging) in human skin
in vivo.
To determine whether IR can induce wrinkles in vivo,
mice were irradiated with IR five times a week for 15
weeks (30 J day
1
) (Kim et al., 2005). We observed that
IR can cause skin wrinkling and augment UV-induced
wrinkle formation through induction of MMPs (Kim et al.,
2005).
IR exposure turns on an angiogenic switch in human skin in vivo
Photoaging is the process whereby skin is prematurely aged
by repeated exposure to solar UV radiation, and skin
angiogenesis plays a critical role in this process (Yano
et al., 2002). Acute UV exposure of human skin is known
to induce angiogenesis, that is, to form new blood vessels, in
human skin. These new vessels are immature and leaky,
resulting in cutaneous inflammation by extravasation of
inflammatory cells and by the inflammatory mediators
produced by these cells. These events may contribute to
further degradation of extracellular matrix proteins, providing
an adverse, less permissive environment for the maintenance
of normal vessel structure and function, leading to progres-
sive loss of cutaneous vessels in photoaged skin (Chung and
Eun, 2007). As is the case with UVB, exposure of human skin
to near-IR induces dermal angiogenesis and alters the
balance between epidermal angiogenic factor (that is, VEGF)
and endogenous angiogenic inhibitor (that is, TSP-2) (Kim
et al., 2006a).
Acute exposure of human skin to IR radiation increases mast
cell number and tryptase expression in human skin in vivo
Mast cells are present in tissues throughout the body but are
most prevalent at sites that are exposed to the environment,
such as skin, airways, and gastrointestinal tract (Metcalfe
et al., 1997). Two types of mature human mast cells have
been described, based on differences in their neutral protease
composition (Irani et al., 1986). MC
T
cells contain tryptase
alone, whereas MC
TC
cells contain tryptase, chymase, and
cathepsin G. UV radiation is considered an extrinsic factor
that can alter the prevalence of mast cells (Grimbaldeston
et al., 2003). Several studies have demonstrated that sun-
exposed human skin has more mast cells than sun-protected
skin (Bhawan et al., 1992; Bosset et al., 2003). Recently, we
also found that the number of mast cells in sun-exposed facial
skin is always significantly higher than that in sun-protected
buttock skin within the same individual (Kim et al., 2009). On
the other hand, the effect of IR on dermal mast cell
prevalence remains unclear at present. We demonstrated
that human skin mast cells are activated and recruited by IR
as well as by UV. After IR irradiation of the buttock skin of
young subjects, the number of MC
TC
was significantly
increased at 24 h post-IR, while the number of MC
T
was not
affected significantly. Tryptase expression was also clearly
upregulated by IR treatment in human skin in vivo (Kim et al.,
2009).
EFFECTS OF HEAT ON AGING PROCESSES IN HUMAN
SKIN IN VIVO
Effects of heat on the expression of MMP-12 in human skin
in vivo
We demonstrated that heat shock induced the expression of
MMP-1 and MMP-3, but not MMP-2, at the mRNA and
protein levels in a dose-dependent manner in cultured
normal human skin fibroblasts through activation of ERK
and JNK and an autocrine IL-6 loop (Park et al., 2004). This
increased expression of MMPs by heat leads to degradation of
extracellular matrix proteins such as collagen and elastic
fibers. Heat is also known to induce MMP-12, which is
capable of destroying the pre-existing elastic fiber network,
thereby contributing to the accumulation of elastotic material
in photoaged skin (Chen et al., 2005). Therefore, heat, like
UV, is a major environmental stimulus that probably plays an
important role in the development of solar elastosis and
premature skin aging.
Effects of heat on the expressions of tropoelastin and fibrillin-1
in human skin in vivo
It has been reported that chronic IR exposure can cause
pronounced elastosis in mouse skin, changes that mimic the
damage caused by UV (Kligman, 1982). It is known that
repeated and prolonged exposure to heat insufficient to
produce a burn causes erythema ab igne, which is
characterized histologically by the basophilic degeneration
of connective tissue and the alteration of elastic fibers, which
resembles elastotic changes in photoaged skin (Hurwitz and
Tisserand, 1987).
16 Journal of Investigative Dermatology Symposium Proceedings (2009), Volume 14
S Cho et al.
IR and Heat Cause Skin Aging
Heat was found to increase tropoelastin mRNA and
protein expression in the epidermis and in the dermis (Chen
et al., 2005). Fibrillin-1 mRNA and protein expression were
increased by heat in the epidermis but were diminished in the
dermis (Chen et al., 2005). Therefore, the abnormal produc-
tion of tropoelastin and fibrillin by heat, like UV, in human
skin and their degradation by various MMPs, such as MMP-
12, may add to the accumulation of elastotic material in
photoaged skin (Chen et al., 2005).
Heat induces angiogenesis in human skin in vivo
IR radiation accounts for approximately 40% of the solar
radiation energy reaching the earth’s surface, subsequently
generating heat and increasing skin temperature. We
demonstrated that heat increases angiogenesis in human skin
in vivo. The ratio of VEGF to TSP-1 and 2 is increased after
heat treatment, leading to increased angiogenesis (Kim et al.,
2006a). Therefore, heat, in addition to UV, is an important
physical stimulus for angiogenesis.
Effects of heat on cytokine expression in human skin
Heat can induce various cytokines in human skin. To
investigate the effects of heat treatment on TGF-bexpression,
human buttock skin was heated for 90 minutes at 431C. The
expression of TGF-b1 and -b2 were increased at 24 hours,
whereas that of TGF-b3 was decreased 24 hours after heat
treatment (Seo and Chung, 2006). Heat treatment also
increased the expression of IL-6 and IL-12 mRNA signifi-
cantly in cultured dermal fibroblasts (Seo and Chung, 2006).
Heat induces various cytokines, and these cytokines in turn
regulate the extracellular matrix protein metabolism in
human skin.
Effects of heat on ROS production
The transcriptional upregulation of MMPs can be mediated
by the increased production of reactive oxygen species
(ROS). UV irradiation induces the formation of ROS in
cutaneous tissue (Kitazawa et al., 1997; Scharffetter-Kocha-
nek et al., 1997). ROS can be generated by many different
organelles in response to various stimuli. Various enzyme
systems including cyclooxygenase, nitric oxide synthase
(NOS), xanthine oxidase, ribonucleotide reductase, mito-
chondrial electron transport systems, and NADPH oxidase
are involved in ROS production (Curtin et al., 2002). Like UV,
heat shock generates H
2
O
2
and O
2
K
(Hall et al., 1994;
Zhang et al., 2003). Heat shock-driven generation of ROS
substantially affects the signaling pathways leading to MMP-1
and MMP-9 induction. Heat shock generates H
2
O
2
and O
2
K
through NADPH oxidase, xanthine oxidase, and the mito-
chondrial electron transport system in HaCaT cells (Shin
et al., 2008). Heat shock-induced O
2
K
is responsible for
MMP-9 expression, whereas H
2
O
2
is involved in the
induction of both MMP-1 and -9 (Shin et al., 2008).
It has been demonstrated that topical application of
antioxidants, genistein or N-acetylcystein, can interrupt the
UV-signaling cascade that leads to photoaging (Kang et al.,
2003). These investigators demonstrated that UV increases
H
2
O
2
in human skin in vivo and that both antioxidants
blocked UV-induced signaling. As heat is known to cause
ROS generation, we investigated the role of ROS in heat-
induced tropoelastin and fibrillin-1 expression (Chen et al.,
2005). We found that pretreatment with N-acetylcystein or
genistein for 24 h prior to heat treatment inhibited the heat-
induced expression of tropoelastin in the epidermis, but not
of fibrillin-1 (Chen et al., 2005). These results indicate that
heat-induced ROS may play a critical role in heat-induced
tropoelastin expression, but not in heat-induced fibrillin-1
expression.
Heat induces oxidative DNA damage in human skin in vivo
UV radiation is absorbed directly by DNA and leads to the
formation of pyrimidine dimers, of which more than 75% are
thymine dimers (Patrick, 1977). UV radiation produces ROS.
DNA is also susceptible to oxidative damage, and 8-oxo-dG
is a useful biomarker of oxidative damage in DNA (Pelle
et al., 2003). As heat shock in human skin can produce ROS,
we investigated the effects of heat shock on DNA damage in
human skin in vivo. Interestingly, heat shock at 431C for
90 minutes, like UV irradiation, increased the 8-oxo-dG in
the epidermis and dermis of human skin in vivo maximally at
24 hours post-heat (Figure 1a). However, heat shock, unlike
UV, did not produce thymidine dimer formation (Figure 1b).
Therefore, heat-induced ROS induce cumulative DNA
damage through oxidative damage.
The effects of IR and heat in the natural sunlight on human skin
In addition to UV radiation, IR plus visible light and the heat
energy generated by sunlight exposure induce MMP-1
expression after exposing human skin to natural sunlight
(Cho et al., 2008). IR plus visible light also increase MMP-9
expression and decrease type I procollagen synthesis after
exposure to natural sunlight (Cho et al., 2008). Only UV
radiation within natural sunlight results in neutrophil infiltra-
tion in human skin at least at 24 hours after exposure,
whereas IR radiation and heat, in addition to UV, can recruit
macrophages.
TRPV1 in the keratinocytes as a heat sensor
Transient receptor potential vanilloid (TRPV) ion channels are
a large family of nonselective cation channels that are
expressed in human keratinocytes, and they are known
to be activated by capsaicin, noxious heat, and low pH
(Szallasi and Blumberg, 1999). TRPV1 itself is known to
be a heat sensor. TRPV1 can be activated by noxious heat
with a threshold of about 431C (Hayes et al., 2000). However,
the function of TRPV1 in cutaneous physiology and
pathology has not been elucidated. Recently, we found
that activation of TRPV1 by heat shock mediates the heat
shock-induced MMP-1 expression in HaCaT cells (Li et al.,
2007; Lee et al., 2008). TRPV1 plays an important role
in heat shock-induced MMP-1 expression, and a calcium-
dependent PKCasignaling is required for heat shock-induced
MMP-1 expression in human keratinocytes (Li et al., 2007;
Lee et al., 2008). Therefore, the TRPV-1 inhibitory compound
would be a good candidate to prevent heat-induced skin
aging.
www.jidonline.org 17
S Cho et al.
IR and Heat Cause Skin Aging
CONCLUSION
Recent evidence indicates that IR and heat may induce
premature skin aging, just like UV radiation: (1) IR exposure
of human skin stimulates the expression of MMP-1 and
decreases type I procollagen expression in vivo. Acute IR
irradiation also increases new, leaky vessel formation and
induces inflammatory cellular infiltration. (2) Heat energy,
which increases skin temperature, also increases MMP-1, -3,
and -12, and modulates elastin and fibrillin synthesis,
resulting in the development of solar elastosis. Acute heat
shock in human skin stimulates new vessel formation, recruits
inflammatory cells, and causes oxidative DNA damage.
Based on these observations, it can be concluded that IR
and heat are important physical stimuli that may cause aging
in human skin. Therefore, in addition to sunscreen to block
the effects of UV, novel strategies to block IR- and heat-
induced skin aging need to be developed to prevent skin
aging more completely. TRPV-1 may be a good target for
preventing heat-induced skin aging (thermal skin aging) in
human skin in vivo.
CONFLICT OF INTEREST
The authors state no conflict of interest.
ACKNOWLEDGMENTS
This research was supported by a Grant (R11-2002-097-06001-0) through the
Center for Aging and Apoptosis Research at Seoul National University from
the Korean Science & Engineering Foundation (KOSEF).
REFERENCES
Bhawan J, Oh CH, Lew R, Nehal KS, Labadie RR, Tsay A et al. (1992)
Histopathologic differences in the photoaging process in facial versus
arm skin. Am J Dermatopathol 14:224–30
Bosset S, Bonnet-Duquennoy M, Barre P, Chalon A, Kurfurst R, Bonte F et al.
(2003) Photoageing shows histological features of chronic skin inflam-
mation without clinical and molecular abnormalities. Br J Dermatol
149:826–35
Chen Z, Seo JY, Kim YK, Lee SR, Kim KH, Cho KH et al. (2005) Heat
modulation of tropoelastin, fibrillin-1, and matrix metalloproteinase-12
in human skin in vivo.J Invest Dermatol 124:70–8
Cho S, Lee MJ, Kim MS, Lee S, Kim YK, Lee DH et al. (2008) Infrared plus
visible light and heat from natural sunlight participate in the expression
UV (2 MED)
Heat (43°C, 90 minutes)
UV (2 MED)
Heat (43°C, 90 minutes)
Control 4 hours
2 hours 8 hours 24 hours
Control 4 hours2 hours 8 hours 24 hours
Control 4 hours2 hours 8 hours 24 hours
Control 4 hours2 hours 8 hours 24 hours
Figure 1.The effects of heat shock and UV on DNA damage in human skin in vivo.Human buttock skin was treated with heat shock at 431C for 90 minutes or 2
MED of UV, and then obtained at indicated time points. The skin specimens were stained immunohistochemically using (a) anti- 8-hydroxy-20-deoxyguanosine
(Oxis International Inc., Foster City, CA) and (b) anti-thymidine dimer antibodies (Kamiya Co., Seattle, WA), respectively (n¼5). Bar ¼20 mm.
18 Journal of Investigative Dermatology Symposium Proceedings (2009), Volume 14
S Cho et al.
IR and Heat Cause Skin Aging
of MMPs and type I procollagen as well as infiltration of inflammatory
cell in human skin in vivo.J Dermatol Sci 50:123–33
Chung JH, Eun HC (2007) Angiogenesis in skin aging and photoaging.
J Dermatol 34:593–600
Chung JH, Seo JY, Choi HR, Lee MK, Youn CS, Rhie G et al. (2001)
Modulation of skin collagen metabolism in aged and photoaged human
skin in vivo.J Invest Dermatol 117:1218–24
Chung JH, Seo JY, Lee MK, Eun HC, Lee JH, Kang S et al. (2002) Ultraviolet
modulation of human macrophage metalloelastase in human skin
in vivo.J Invest Dermatol 119:507–12
Curtin JF, Donovan M, Cotter TG (2002) Regulation and measurement of
oxidative stress in apoptosis. J Immunol Methods 265:49–72
Fisher GJ, Datta SC, Talwar HS, Wang ZQ, Varani J, Kang S et al. (1996)
Molecular basis of sun-induced premature skin ageing and retinoid
antagonism. Nature 379:335–9
Fisher GJ, Wang ZQ, Datta SC, Varani J, Kang S, Voorhees JJ (1997)
Pathophysiology of premature skin aging induced by ultraviolet light.
N Engl J Med 337:1419–28
Grimbaldeston MA, Simpson A, Finlay-Jones JJ, Hart PH (2003) The effect of
ultraviolet radiation exposure on the prevalence of mast cells in human
skin. Br J Dermatol 148:300–6
Hall DM, Buettner GR, Matthes RD, Gisolfi CV (1994) Hyperthermia
stimulates nitric oxide formation: electron paramagnetic resonance
detection of .NO-heme in blood. J Appl Physiol 77:548–53
Hayes P, Meadows HJ, Gunthorpe MJ, Harries MH, Duckworth DM, Cairns
Wet al. (2000) Cloning and functional expression of a human orthologue
of rat vanilloid receptor-1. Pain 88:205–15
Hurwitz RM, Tisserand ME (1987) Erythema ab igne. Arch Dermatol 123:21–3
Irani AA, Schechter NM, Craig SS, DeBlois G, Schwartz LB (1986) Two types
of human mast cells that have distinct neutral protease compositions.
Proc Natl Acad Sci USA 83:4464–8
Kang S, Chung JH, Lee JH, Fisher GJ, Wan YS, Duell EA et al. (2003) Topical
N-acetyl cysteine and genistein prevent ultraviolet-light-induced signal-
ing that leads to photoaging in human skin in vivo.J Invest Dermatol
120:835–41
Kim HH, Lee MJ, Lee SR, Kim KH, Cho KH, Eun HC et al. (2005)
Augmentation of UV-induced skin wrinkling by infrared irradiation in
hairless mice. Mech Ageing Dev 126:1170–7
Kim MS, Kim YK, Lee DH, Seo JE, Cho KH, Eun HC et al. (2009) Acute
exposure of human skin to ultraviolet light, infrared ray or heat stimuli
increases mast cell numbers and tryptase expression in human skin
in vivo.Br J Dermatol 160:393–402
Kim MS, Kim YK, Cho KH, Chung JH (2006a) Infrared exposure induces an
angiogenic switch in human skin that is partially mediated by heat. Br J
Dermatol 155:1131–8
Kim MS, Kim YK, Cho KH, Chung JH (2006b) Regulation of type I procollagen
and MMP-1 expression after single or repeated exposure to infrared
radiation in human skin. Mech Ageing Dev 127:875–82
Kitazawa M, Podda M, Thiele J, Traber MG, Iwasaki K, Sakamoto K et al.
(1997) Interactions between vitamin E homologues and ascorbate free
radicals in murine skin homogenates irradiated with ultraviolet light.
Photochem Photobiol 65:355–65
Kligman LH (1982) Intensification of ultraviolet-induced dermal damage by
infrared radiation. Arch Dermatol Res 272:229–38
Lee HS, Lee DH, Cho S, Chung JH (2006) Minimal heating dose: a novel
biological unit to measure infrared irradiation. Photodermatol Photo-
immunol Photomed 22:148–52
Lee YM, Li WH, Kim YK, Kim KH, Chung JH (2008) Heat-induced MMP-1
expression is mediated by TRPV1 through PKCalpha signaling in HaCaT
cells. Exp Dermatol 17:864–70
Li WH, Lee YM, Kim JY, Kang S, Kim S, Kim KH et al. (2007) Transient
receptor potential vanilloid-1 mediates heat-shock-induced matrix
metalloproteinase-1 expression in human epidermal keratinocytes.
J Invest Dermatol 127:2328–35
Massague J (1998) TGF-beta signal transduction. Annu Rev Biochem
67:753–91
Metcalfe DD, Baram D, Mekori YA (1997) Mast cells. Physiol rev 77:
1033–1079
Park CH, Lee MJ, Ahn J, Kim S, Kim HH, Kim KH et al. (2004) Heat shock-
induced matrix metalloproteinase (MMP)-1 and MMP-3 are mediated
through ERK and JNK activation and via an autocrine interleukin-6 loop.
J Invest Dermatol 123:1012–9
Patrick MH (1977) Studies on thymine-derived UV photoproducts in DNA—I.
Formation and biological role of pyrimidine adducts in DNA. Photo-
chem Photobiol 25:357–72
Pelle E, Huang X, Mammone T, Marenus K, Maes D, Frenkel K (2003)
Ultraviolet-B-induced oxidative DNA base damage in primary normal
human epidermal keratinocytes and inhibition by a hydroxyl radical
scavenger. J Invest Dermatol 121:177–83
Scharffetter-Kochanek K, Wlaschek M, Brenneisen P, Schauen M,
Blaudschun R, Wenk J (1997) UV-induced reactive oxygen
species in photocarcinogenesis and photoaging. Biol Chem 378:
1247–1257
Schieke S, Stege H, Kurten V, Grether-Beck S, Sies H, Krutmann J (2002)
Infrared-A radiation-induced matrix metalloproteinase 1 expression is
mediated through extracellular signal-regulated kinase 1/2 activation in
human dermal fibroblasts. J Invest Dermatol 119:1323–9
Schieke SM, Schroeder P, Krutmann J (2003) Cutaneous effects of infrared
radiation: from clinical observations to molecular response mechanisms.
Photodermatol Photoimmunol Photomed 19:228–34
Seo J, Chung J (2006) Thermal aging: A new concept of skin aging. J Dermatol
Sci suppl 2:S13–22
Shin MH, Moon YJ, Seo JE, Lee Y, Kim KH, Chung JH (2008) Reactive oxygen
species produced by NADPH oxidase, xanthine oxidase, and mitochon-
drial electron transport system mediate heat shock-induced MMP-1 and
MMP-9 expression. Free Radic Biol Med 44:635–45
Szallasi A, Blumberg PM (1999) Vanilloid (Capsaicin) receptors and
mechanisms. Pharmacol Rev 51:159–212
Varani J, Warner RL, Gharaee-Kermani M, Phan SH, Kang S, Chung JH et al.
(2000) Vitamin A antagonizes decreased cell growth and
elevated collagen-degrading matrix metalloproteinases and stimulates
collagen accumulation in naturally aged human skin. J Invest Dermatol
114:480–6
Yano K, Oura H, Detmar M (2002) Targeted overexpression of the
angiogenesis inhibitor thrombospondin-1 in the epidermis of transgenic
mice prevents ultraviolet-B-induced angiogenesis and cutaneous photo-
damage. J Invest Dermatol 118:800–5
Zhang HJ, Xu L, Drake VJ, Xie L, Oberley LW, Kregel KC (2003) Heat-induced
liver injury in old rats is associated with exaggerated oxidative stress and
altered transcription factor activation. FASEB J 17:2293–5
www.jidonline.org 19
S Cho et al.
IR and Heat Cause Skin Aging
... Direct sunlight can raise the temperature of human skin from 37 °C to 40 °C, with darker skin types IV-VI responding to IR exposure with greater rises in temperature than experienced by light-skinned individuals (types I and II). Although more than 65% of incipient IR-A penetrates to the dermis and 10% to the subcutaneous fat, normal (non-excessive) exposure does not raise the skin's temperature [12] . ...
... The reaction to IR-A varies with skin type: In darker skin, melanin synthesis is stimulated with little effect in dermal MMPs, while in lightly pigmented skin, collagen in the dermal extracellular matrix is altered not only by destruction through activation of MMPs, but also by a direct reduction in synthesis [12] . Thus lightly pigmented skin manifests wrinkles and a crepe-like quality, while darkly pigmented skin responds with increased solar lentigos -both suffering from premature extrinsic aging. ...
... Thus lightly pigmented skin manifests wrinkles and a crepe-like quality, while darkly pigmented skin responds with increased solar lentigos -both suffering from premature extrinsic aging. In addition, chronic exposure to IR-A induces angiogenesis and unattractive erythema ab igne as seen in "bakers' arms" and "glassblowers' faces" [12] . ...
Article
Full-text available
The appearance of aging is determined primarily by extrinsic factors through exposure to environmental sunlight and airborne pollution. That solar ultraviolet B (λ = 290-320 nm) directly causes photoaging (with wrinkles, dryness, and mottled pigmentation) and skin cancer has been recognized for decades; the contribution by ultraviolet A (λ = 320-400 nm) was only more recently understood. New research further implicates visible light (λ = 400-700 nm) as well as the heat rays of infrared radiation (λ > 800 nm). Particularly in urban environments, airborne pollutants such as ozone (O3), polycyclic aromatic hydrocarbons, particulate matter (PM) in smog, and tobacco smoke contribute to photoaging and skin cancer. Furthermore, exposure simultaneously to both solar ultraviolet (UV) and these pollutants results in even greater synergistic damage. The volatile pollutants generate reactive oxygen species which oxidize surface lipids leading to deeper damaging inflammatory reactions. PM carries high concentrations of environmental organic compounds and trace metals. These pollutant-laden particles deliver toxins to the skin transcutaneously through hair follicles and through the blood after respiratory inhalation. The predominant natural mechanism of clearing these xenobiotic chemicals is through the ligand-activated transcription factor the arylhydrocarbon receptor (AHR) found on all skin cells. AHR activity regulates keratinocyte differentiation and proliferation, maintenance of epidermal barrier function, melanogenesis, and immunity. With chronic activation by UV exposure and pollutants, AHR signaling contributes to both extrinsic aging and carcinogenesis.
... Furthermore, infrared radiation leakage can also be an important consideration for people who want to try this advanced technology because uncontrolled, frequent exposure to infrared can cause some healthy problems such as thermal burns and effects of aging. [87] Thus, the risks and chances coexist in infrared drying technology for goji berry, and further improvements are worth exploring. ...
... The superposition of intrinsic and extrinsic aging, named photoaging, is responsible for 85% of aged skin phenotype in exposed areas. The chronic exposure to aggressors like solar radiation, especially ultra-violet (UV), tobacco, pollution and hot climate causing activation of transient receptor potential cation channel subfamily V member 1 (TrpV1), accelerate the skin aging [10,30]. Additionally, forehead, eyes, and lip areas are affected by superposition of dynamic wrinkles related to muscular activity [31]. ...
Article
Full-text available
Background Skin aging involves genetic, environmental and hormonal factors. Facial wrinkles also depend on muscular activity. Gene expression investigation may be useful for new anti-aging products.Methods and ResultsTo evaluate structure and gene expression differences among exposed and unexposed skin in menopausal women. Cross-sectional study, including 15 menopausal women, 55–65 years, phototype III; photo-exposed, periorbital wrinkles (A1), preauricular, not wrinkled (A2), and unexposed gluteal (A3) areas were described and compared by non-invasive measures, histology, immunohistochemistry and gene expression (RNASeq); participants mean age was 61yo, presenting moderate periorbital wrinkles and light facial photodamage. Higher roughness, wrinkles number and echogenicity were observed in A1 and A2 versus A3. Decreased epidermal thickness and dermal collagen IV were demonstrated in A1 versus A2 and A3. Exposed areas impacted different pathways compared to unexposed. Exposed wrinkled skin (A1) showed impact on cell movement with decreased inflammatory activation state. Pathways related to lipid and aminoacids metabolism were modulated in non-wrinkled exposed (A2) compared to unexposed (A3) skin.Conclusions Expected histological findings and gene expression differences among areas were observed. Photoaging in menopausal women may modulate lipid and aminoacids metabolism and decrease inflammatory and keratinization pathways, cellular homeostasis, immune response, fibrogenesis and filament formation. These findings may help development of new therapies for skin health and aging control.
... The present study examined the effects of the application of ultrasound using a murine model of AA under a finasteride regimen. As ultrasound may induce tissue cavitation or temperature elevation (which may increase local blood flow), both of which could confound the interpretation of the results [18] or have ramifications involving undesired biological effects such as skin injury, premature skin aging, and neuropathic pain [19,20], this study used noncavitational, low-intensity ultrasound that does not elevate the temperature of the sonicated tissue. The degree of hair growth was evaluated using photographic and histological analyses (hematoxylin and eosin [H&E] staining and β-catenin staining). ...
Article
Purpose: The purpose of this study was to evaluate if transcutaneous application of low-intensity ultrasound can locally enhance the effects of finasteride on hair growth in a murine model of androgenic alopecia (AA). Methods: AA mice (injected twice per week with testosterone enanthate, n=11), under daily oral administration of finasteride, received 1-MHz ultrasound for 1 hour at the unilateral thigh area five times per week for 5 weeks. Non-thermal and non-cavitational ultrasound was delivered in a pulsed manner (55-ms pulse duration with a repetition frequency of 4 Hz). Skin temperature was measured during sonication, and the measurements were validated with numerical simulations of sonication-induced tissue temperature changes. Hair growth was assessed both photographically and histologically. Results: We found more hair growth on the sonicated thigh area than on the unsonicated thigh, beginning from week 3 through the end of the experiment. Histological analyses showed that the number of hair follicles doubled in the skin sections that received sonication compared to the unsonicated zone, with thicker follicular diameter and skin. An over five-fold increase was also observed in the anagen/telogen ratio in the sonicated area, suggesting an enhanced anagen phase. Skin temperature was unaltered by the administered sonication. Conclusion: The findings of the present study suggest that pulsed application of ultrasound promotes hair growth, potentially by disrupting the binding of albumin to finasteride. This may suggest further applications to enhance the pharmacological effects of other relevant drugs exhibiting high plasma protein binding.
... The superposition of intrinsic and extrinsic aging, named photoaging, is responsible for 85% of aged skin phenotype in exposed areas. The chronic exposure to aggressors like solar radiation, especially ultra-violet (UV), tobacco, pollution and hot climate causing activation of transient receptor potential cation channel subfamily V member 1 (TrpV1), accelerate the skin aging [11,30]. Additionally, forehead, eyes, and lip areas are affected by superposition of dynamic wrinkles related to muscular activity [31]. ...
Preprint
Full-text available
Skin aging involves genetic, environmental and hormonal factors. Facial wrinkles also depend on muscular activity. Gene expression investigation may be useful for new anti-aging products. To evaluate structure and gene expression differences among exposed and unexposed skin in menopausal women. Cross-sectional study, including 15 menopausal women, 55-65yo, phototype III; photo-exposed, periorbital wrinkles (A1), preauricular, not wrinkled (A2), and unexposed gluteal (A3) areas were described and compared by non-invasive measures, histology, immunohistochemistry and gene expression (RNASeq); participants mean age was 61yo, presenting moderate periorbital wrinkles and light facial photodamage. Higher roughness, wrinkles number and echogenicity were observed in A1 and A2 versus A3. Decreased epidermal thickness and dermal collagen IV were demonstrated in A1 versus A2 and A3. Exposed areas impacted different pathways compared to unexposed. Exposed wrinkled skin (A1) showed impact on cell movement with decreased inflammatory activation state. Pathways related to lipid and aminoacids metabolism were modulated in non-wrinkled exposed (A2) compared to unexposed (A3) skin. Expected histological findings and gene expression differences among areas were observed. Photoaging in menopausal women may modulate lipid and aminoacids metabolism and decrease inflammatory and keratinization pathways, cellular homeostasis, immune response, fibrogenesis and filament formation. These findings may help development of new therapies for skin health and aging control.
... For the human body, light is both beneficial and harmful. Too much exposure can result in DNA damage, premature aging, and skin cancer formation [1][2][3][4]. Conversely, light can prevent vitamin D deficiency, promote wound healing, and treat/cure cutaneous infections and other skin conditions [4][5][6][7]. With the advent of lasers, light has emerged as a useful medical tool for harnessing the biomedical effects of photothermal, photomechanical, and photochemical interactions to treat specific conditions including cancer. ...
Article
Full-text available
Immunotherapy has provided a new avenue to treat metastatic cancers, which result in ∼90% of cancer related deaths. However, current immunotherapies, such as immune checkpoint therapy (ICT), have met with limited success, primarily due to tumor intrinsic and extrinsic factors that inhibit antitumor immune responses. To overcome the immune suppression of the tumor microenvironment (TME) and enhance the tumoricidal activity of ICT, phototherapy, particularly photothermal therapy (PTT), combined with nanomedicine has become a viable option. PTT disrupts target tumor homeostasis, releasing tumor associated antigens (TAAs), tumor specific antigens (TSAs), danger associated molecular patterns (DAMPs), and scarce nutrients required to “feed” activated antitumor immune cells. While nanoparticles localize and specify the phototherapeutic effect, they can also be loaded with immune stimulants, TME modulators, and/or chemotherapeutic agents to greatly enhance immune stimulation and tumor killing. Combining these three technologies, which we term nano-ablative immunotherapy (NAIT), with ICT can greatly enhance their therapeutic effects. In this review, we will discuss the successes and limitations of NAIT + ICT. Specifically, we will discuss how the TME limits tumoricidal activity and what should be considered to overcome these limitations.
Article
Diimmonium dye is one of the representative near-infrared (NIR) absorbing dyes. In general, diimmonium dyes, constructed with a cationic backbone and two counter anions, show strong and broad absorption in the near-infrared region. In this study, a series of diimmonium dyes were synthesized with varying types of counter anions, and the dependence of material properties of diimmonium dyes on the type of counter anions was investigated. The diimmonium dyes showed different colors in the solid-state as the crystal structures of dyes were change by the type of counter anions. One of the diimmonium dyes, DB-TFSI, showed the highest thermal stability and molar absorptivity because of the formation of a strong complex structure between the cationic backbone and TFSI, whose negative charges were extensively distributed over the whole molecule. A monatomic anion such as chloride did not form a strong complex structure, so that it showed low thermal stability and NIR absorbing ability. As the solvent polarity increased, the molar absorptivity of diimmonium dyes decreased due to the dissociation of counter-anions. The characteristic optical properties and solvatochromic behavior were also observed in NIR absorbing films made of the diimmonium dyes and a transparent polymeric binder. Thus, it is demonstrated by this study that the materials properties of diimmonium dyes are affected by the degree of charge distribution of counter anions, and the weakly coordinating anions such as TFSI are effective to improve the materials properties.
Chapter
This chapter provides an overview of the most important skin exposome factors impacting skin aging and discusses the role of exposome factors in specific skin conditions such as atopic dermatitis, and acne. It includes some suggestions on how to limit impact of the exposome on skin. Skin aging combines two processes: intrinsic aging, the normal genetic processes that occur with time, and extrinsic aging, or accelerated aging, from exposure to skin exposome factors. The chapter focuses on exposome factors directly implicated in skin aging: exposure to solar radiation, air pollution, and tobacco smoking. The skin is directly affected by climate change, such as fluctuating humidity and temperature, and changes in the amount and type of irradiation. Climate change is expected to increase the impact of solar rays resulting in accelerated photoaging and increased incidences of certain skin cancers. A daily cosmetic skin care routine can help correct and prevent the negative effects of exposome exposure.
Article
Clothing is recognized by leading health agencies as a primary method to protect against the harmful effects of photodamage caused by ultraviolet (UV) radiation and visible light. The photoprotective capacity of clothing is commonly measured as the ultraviolet protective factor (UPF). While the technology driving photoprotective clothing has been well‐established, there continues to be efforts to discover new materials to improve the UPF of clothing. Here, we show increased Google searches for photoprotective clothing over the last decade, suggesting a high level of public interest in photoprotective clothing. In addition, we investigate the frequency of UPF‐graded photoprotective clothing sold by large retail stores featured in Fortune 1000. We review factors that alter the UPF of clothing and describe emerging textile technologies used to increase clothing’s photoprotective capacity. Finally, we compare how photoprotective clothing is regulated among different countries, the importance of photoprotective clothing in occupational health, and research in visible light and clothing photoprotection.
Chapter
Skin aging is a complex process with variable factors influencing the aging process including genetics, environment and lifestyle. Skin structure, function, and the appearance of aging varies in different ethnicities. Skin is subjected to internal and external factors such as sun exposure and climate conditions. Due to the great variation in genetic diversity, climate, and culture, the signs associated with aging may also vary greatly between various ethnicities. For instance, in Asia with its vast territory, large population, and diverse cultures, there are big differences in signs of aging including pigmentation, wrinkles, and photoaging. Skin aging and skincare including protection, cosmeceuticals, topical anti-aging components, antioxidants, and peptides are discussed.
Article
To the Editor.— The clinical manifestations of erythema ab igne are well known and consist of a reticulated red or brown macular eruption resulting from infrared radiation, occurring most commonly on the lower legs and backs of women. The initial manifestation is erythema, which eventuates into dusky brown macular bands and is usually associated with mild symptoms such as itching and burning.1 We had the opportunity to perform a critical histopathologic study on skin biopsy specimens taken from early red and later dusky brown patches from the backs of two women with classic erythema ab igne. Report of Cases.—Case 1.— A 48-year-old obese woman presented to our office with a reticulated macular eruption on the lower aspect of the back that was mildly tender and pruritic. She had had chronic low back pain secondary to degenerative disk disease for 20 years, and had undergone surgery in 1966, 1975
Article
Damage to human skin due to ultraviolet light from the sun (photoaging) and damage occurring as a consequence of the passage of time (chronologic or natural aging) are considered to be distinct entities. Photoaging is caused in part by damage to skin connective tissue by increased elaboration of collagen-degrading matrix metalloproteinases, and by reduced collagen synthesis. As matrix metalloproteinase levels are known to rise in fibroblasts as a function of age, and as oxidant stress is believed to underlie changes associated with both photoaging and natural aging, we determined whether natural skin aging, like photoaging, gives rise to increased matrix metalloproteinases and reduced collagen synthesis. In addition, we determined whether topical vitamin A (retinol) could stimulate new collagen deposition in sun-protected aged skin, as it does in photoaged skin. Sun-protected skin samples were obtained from 72 individuals in four age groups: 18-29 y, 30-59 y, 60-79 y, and 80+ y. Histologic and cellular markers of connective tissue abnormalities were significantly elevated in the 60-79 y and 80+ y groups, compared with the two younger age groups. Increased matrix metalloproteinase levels and decreased collagen synthesis/expression were associated with this connective tissue damage. In a separate group of 53 individuals (80+ y of age), topical application of 1% vitamin A for 7 d increased fibroblast growth and collagen synthesis, and concomitantly reduced the levels of matrix-degrading matrix metalloproteinases. Our findings indicate that naturally aged, sun-protected skin and photoaged skin share important molecular features including connective tissue damage, elevated matrix metalloproteinase levels, and reduced collagen production. In addition, vitamin A treatment reduces matrix metalloproteinase expression and stimulates collagen synthesis in naturally aged, sun-protected skin, as it does in photoaged skin.
Article
The mechanism of oxidation of ascorbic acid in mouse skin homogenates by UV light was investigated by measuring ascorbate free radical formation using electron spin resonance signal formation. Addition of vitamin E (α-tocopherol or α-tocotrienol) had no effect, whereas short-chain homologues (2,5,7,8-tetramethyl-6-hydroxy-chroman-2-carboxylic acid [Trolox] and 2,2,5,7,8-penta-methyl-6-hydroxychromane [PMC]) accelerated ascorbate oxidation. The similar hydrophilicity of ascorbate, Trolox and PMC increased their interaction, thus rapidly depleting ascorbate. When dihydrolipoic acid was added simultaneously with the vitamin E homologues, the accelerated ascorbate oxidation was prevented. This was due to the regeneration of ascorbate and PMC from their free radicals by a recycling mechanism between ascorbate, vitamin E homologues and dihydrolipoic acid. Potentiation of antioxidant recycling may be protective against UV irradiation-induced damage. The rate of ascorbate oxidation in the presence of vitamin E homologues was enhanced by a photosensitizer (riboflavin) but was not influenced by reactive oxygen radical quenchers, superoxide dismutase or 5,5-dimethyl-l-pyrroline-iV-ox-ide. These experimental results suggest that the UV irradiation-induced ascorbate oxidation in murine skin homogenates is caused by photoactivated reactions rather than reactive oxygen radical reactions.
Article
Abstract— Pyrimidine (Pyr) adducts constitute a significant fraction of the photoproducts formed in DNA exposed to far UV light. The primary and secondary DNA structure affects the rate of Pyr adduct formation; for example, it increases with decreasing (Ade + Thy)/(Gua + Cyt) of the DNA and with increasing dehydration, and it is greater in double-stranded than in single-stranded DNA. Pyrimidine adducts do not appear to be involved in inter-strand cross-links, and 313 nm-induced photolysis of Pyr adducts does not cause strand breakage. The action spectrum for Pyr adduct formation is qualitatively similar to that for Pyr < > Pyr formation; the calculated quantum yields for its formation is essentially wavelength independent over the range 254 nm to 280 nm, but decreased somewhat at shorter wavelengths (240 nm). The biological role of Pyr adducts is still not clear. The data suggest that either Pyr adducts and their photolysis products are not lethal, or that both are lethal but can be repaired under certain conditions.
Article
BackgroundSunlight damages human skin, resulting in a wrinkled appearance. Human skin temperature, measured inside the dermis by a needle-type thermometer, can be increased up to about 40 °C in direct summer midday sunlight within 15–20 min, and this heat may contribute significantly to sun-induced skin damage. Recent studies suggest that heat as well as UV may play an important role in premature skin aging. However, our knowledge about the effects of heat or infrared light, which certainly increase the temperature of the skin and may possibly interfere with or enhance the damaging effects of UV, on the development of skin aging is limited.ObjectivesThis review provides an outline of the thermal effects on skin aging process in human skin.
Article
Mast cells are key effector cells in diverse immunological and pathological processes. It is still unclear why there are more mast cells at peripheral and sun-exposed skin sites than at sun-protected sites. To investigate changes in mast cell numbers associated with natural ageing and photoageing, and to observe the effects of ultraviolet (UV) and infrared (IR) radiation and heat on the prevalence of mast cells and tryptase expression in human skin in vivo. Sun-exposed and sun-protected skin samples were taken from individuals in four different age groups. UV, IR or heat-treated buttock skin of young volunteers was also obtained. Mast cells were quantified by immunohistochemical staining of mast cell-specific tryptase and chymase. The expression of tryptase was determined by Western blotting. Both sun-exposed and sun-protected skin showed a gradual decrease in total mast cells (MC(Total)) number with ageing. The number of mast cells in sun-exposed skin was significantly higher than that in sun-protected skin. After UV irradiation (2 minimal erythema doses), MC(Total) and mast cells expressing tryptase and chymase were significantly increased at 24 and 48 h postirradiation. After IR irradiation (3 minimal heating doses) and heat treatment (43 degrees C for 90 min), MC(Total) reached peak induction at 8 and 48 h after stimulation, respectively. Tryptase expression was also clearly upregulated by UV, IR and heat. Our data demonstrate that mast cell numbers decreased with ageing in human skin. Also, mast cells may be activated and recruited by UV, IR and heat. These findings should further our understanding of the reason for the high prevalence of mast cells at peripheral sun-exposed skin sites.