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Rejuvenation of Gene Expression Pattern of Aged Human Skin by Broadband Light Treatment: A Pilot Study

  • Advanced Aesthetic Dermatology

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Studies in model organisms suggest that aged cells can be functionally rejuvenated, but whether this concept applies to human skin is unclear. Here we apply 3'-end sequencing for expression quantification ("3-seq") to discover the gene expression program associated with human photoaging and intrinsic skin aging (collectively termed "skin aging"), and the impact of broadband light (BBL) treatment. We find that skin aging was associated with a significantly altered expression level of 2,265 coding and noncoding RNAs, of which 1,293 became "rejuvenated" after BBL treatment; i.e., they became more similar to their expression level in youthful skin. Rejuvenated genes (RGs) included several known key regulators of organismal longevity and their proximal long noncoding RNAs. Skin aging is not associated with systematic changes in 3'-end mRNA processing. Hence, BBL treatment can restore gene expression pattern of photoaged and intrinsically aged human skin to resemble young skin. In addition, our data reveal, to our knowledge, a previously unreported set of targets that may lead to new insights into the human skin aging process.Journal of Investigative Dermatology advance online publication, 30 August 2012; doi:10.1038/jid.2012.287.
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Rejuvenation of Gene Expression Pattern of
Aged Human Skin by Broadband Light Treatment:
A Pilot Study
Anne Lynn S. Chang
, Patrick H. Bitter Jr
, Meihong Lin
, Nicole A. Rapicavoli
and Howard Y. Chang
Studies in model organisms suggest that aged cells can be functionally rejuvenated, but whether this concept
applies to human skin is unclear. Here we apply 3
-end sequencing for expression quantification (‘‘3-seq’’) to
discover the gene expression program associated with human photoaging and intrins ic skin aging (collectively
termed ‘skin aging’’), and the impact of broadband light (BBL) treatment. We find that skin aging was associated
with a significantly altered ex pression level of 2,265 coding and noncoding RNAs, of which 1,293 became
‘rejuvenated’ after BBL treatment; i.e., they became more similar to their expression level in youthful skin.
Rejuvenated genes (RGs) included several known key regulators of organismal longevity and their proximal
long noncoding RNAs. Skin aging is not associated with systematic changes in 3
-end mRNA processing. Hence,
BBL treatment can restore gene expression pattern of photoaged and intrinsically aged human skin to resemble
young skin. In addition, our data reveal, to our knowledge, a previously unreported set of targets that may lead
to new insights into the human skin aging process.
Journal of Investigative Dermatology (2013) 133, 394–402; doi:10.1038/jid.2012.287; published online 30 August 2012
Aging is under complex genetic and environmental control.
Aging is associated with large-scale changes in gene
expression, and how such changes may be modulated for
healthful benefits in human beings is not clear. Numerous
single-gene mutations have been identified that can extend
the lifespan of model organisms (Partridge, 2010; de
Magalhaes et al., 2012), and dietary restriction can slow the
rate of aging, even if applied late in life (Partridge, 2010).
More recently, several interventions have been shown to
confer features of youthfulness to aged cells or tissues,
demonstrating a remarkable plasticity of the aging process.
For instance, heterochronic parabiosis between young and
old mice enables circulatory factors to restore the functions of
aged muscle stem cells (Liu and Rando, 2011). Similarly,
inducible blockade of the transcription factor NF-kB in aged
murine epidermis can abrogate cellular senescence and
restore the global gene expression program of old skin to
resemble that of young skin (Adler et al., 2007). An important
question is whether similar plasticity exists in human skin,
where aging occurs over decades rather than over months or
years as seen in model organisms. Defining clinically viable
strategies to unlock the plasticity of human aging is a critical
An ideal technology to test this concept is broadband light
(BBL), also known as intense pulse light, a commonly available
and popular treatment to ‘‘rejuvenate’’ the skin. According to
the American Society for Aesthetic Plastic Surgery, over $215
million dollars were spent in the United States in 2009 on
these procedures. Unlike ablative light-based treatments that
improve the overall appearance of aged skin through thermal
destruction and regrowth of the epidermis and superficial
dermis, BBL uses a broad band of noncoherent light waves,
ranging from 560 to 1,200 nm, that are absorbed by a number
of components in the skin. Currently, BBL procedures are used
to decrease the appearance of fine rhytides, dyspigmentation,
erythema, and elastosis (Bitter Jr, 2000; Negishi et al., 2001).
Nevertheless, the molecular changes that are induced by this
treatment are unclear.
‘‘Rejuvenation’’ is a term that has been used by many
investigators and the lay public with different meanings, and thus
needs to be carefully defined. Here we define ‘‘rejuvenation’’ as
the restoration of characteristics of youthfulness to aged cells and
tissues. After BBL treatment, is the skin truly ‘‘rejuvenated’’ at a
molecular level, i.e., more closely resembles younger skin, or is
the treatment merely inducing a wounding or scarring response
that differs fundamentally from uninjured youthful skin?
394 Journal of Investigative Dermatology (2013), Volume 133 & 2013 The Society for Investigative Dermatology
Received 19 February 2012; revised 19 June 2012; accepted 11 July 2012;
published online 30 August 2012
This study was accepted as a poster presentation at the 2012 Society of
Investigative Dermatology Annual Meeting
Department of Dermatology, Stanford University School of Medicine,
Redwood City, California, USA;
Advanced Aesthetic Dermatology, Los
Gatos, California, USA and
Howard Hughes Medical Institute, Stanford,
California, USA
Correspondence: Anne Lynn S. Chang, Department of Dermatology, Stanford
University School of Medicine, 450 Broadway Street, MC 5334, Redwood
City, California 94063, USA. E-mail:
Abbreviations: BBL, broadband light; GO, Gene Ontology; lncRNA, long
noncoding RNA; polyA, polyadenylated; qRT–PCR, quantitative reverse
transcription–PCR; RG, rejuvenated gene; 3-seq, 3
-end sequencing for
expression quantification
Histologically, BBL has been reported to diminish melanin
deposition in the dermis and reduce telangiectasias (Bitter Jr,
2000; Prieto et al., 2002), with some reports also reporting an
increase in new upper papillary dermal collagen formation at
3 weeks after treatment (Negishi et al., 2001). However, this
neocollagen formation may be a more variable or short-term
effect, as ultrastructural analyses of skin 3 months after
treatment have not shown any collagen or elastin fiber effects
(Prieto et al., 2002). We examine the molecular basis of the
BBL treatment response by defining the global gene expres-
sion programs of photoaged and intrinsically aged human
skin and response to BBL. The intent is to capture the
broadest spectrum of changes in RNA induced by aging and
BBL, including alterations in gene expression (coding and
noncoding) and gene regulation.
Clinical and histologic changes after BBL treatment
To gain insights into the gene expression program associated
with skin aging and BBL treatment, we used skin biopsies
from young female volunteers (age o30 years, n ¼ 5) and
site-matched untreated and treated skin of aged female
volunteers (age 450 years, n ¼ 5), the latter after three
courses of monthly BBL treatment (n ¼ 5; Figure 1a). The
treated subjects were healthy older females with moderate to
severe photodamage on the forearms, and resided in the
Santa Clara or San Jose, California metropolitan area, where
on average there are 257 sunny days out of 365 days, with the
average UV Index being 5.1 (average UV Index in the United
States is 4.3; source:, accessed 25 April
2012). Tanning beds, topical retinoids, or any other skin
treatments on the arms were prohibited for 1 month before
enrollment and during the study. During the study, the
participants were instructed to sun-protect their arms with a
broad-spectrum sunscreen and long-sleeved clothing, as well
as avoid prolonged sun exposure. The untreated young
subjects had the same inclusion criteria, but did not have
evidence of photoaging on the arms.
After three BBL treatments, arm skin showed improve-
ments in clinical ratings of intrinsic and extrinsic skin aging
parameters: fine wrinkling ( P ¼ 0.03), abnormal pigmentation
(P ¼ 0.02), and global skin aging assessment (P ¼ 0.01; Figure
1a–c). On histologic examination, the elastotic fibers in the
treated aged samples were found to be diminished and less
distinct compared with those in untreated aged samples
(Figure 1d–g). The periodic acid–Schiff stain showed no
obvious changes in collagen quantity in the dermis between
treated and untreated aged samples, although they did appear
less disordered after treatment (Figure 1h and i). The treated
aged samples also displayed subjective increases in epider-
mal thickness (Figure 1e, g and i) compared with untreated
aged samples (Figure 1d, f and h).
Expression program of coding and noncoding RNAs in aging
Although gene expression programs of aging in several tissues
have been previously examined by microarray hybridization,
we used 3
-end sequencing for expression quantification
(3-seq), an efficient strategy of deep sequencing of RNA
ends (Tariq et al., 2011). The potential advantages of 3-seq
include accurate quantification of transcript levels not
obscured by cross-hybridization, an ability to determine
alterations in RNA termination and processing, and the ability
to discover previously unannotated genes, such as long
noncoding RNAs (lncRNAs). We generated 6.5–12.4 million
uniquely mappable reads for each sample, and identified
differentially expressed transcripts using DESeq algorithm
(see Materials and Methods).
To rigorously define aging in molecular terms, we first
identified transcript alterations associated with aging by com-
paring untreated young with untreated aged samples, and then
tested how BBL treatment to aged skin affected these parameters.
Comparison of mRNA transcript levels in untreated young
versus untreated aged, as well as untreated aged versus
treated aged, samples revealed a consistent significant
change in the expression level in 3,530 genes (Figure 2a).
The directionality of the gene expression change with BBL
treatment is shown in Figure 2a, with blue indicating a 2-fold
decrease and yellow indicating a 2-fold increase. Genes
whose transcript levels changed significantly between un-
treated young and untreated aged (n ¼ 2,265) are shown in
Supplementary Table S1 online.
To visually display the locations of significant genes on the
large heat map (Figure 2a), we have provided columns (in
magenta) to the right of the large heat map that represent
biological themes, according to Gene Ontology (GO) terms.
For instance, the ‘‘rejuvenated genes’’ (RGs) and lncRNAs
are distributed on both the upper and lower parts of the
large heat map. In contrast, the ‘‘immune response’’ genes
and ‘‘translation’’ genes are located on the lower half of
the heat map. The ‘‘cell adhesion’’ genes are located on
the upper half of the large heat map and are decreased
in the untreated young group, increased in the untreated
aged group, and intermediate in the treated aged group. The
magenta columns hence provide a general sense of what
biological function is altered and in what direction (increased
(yellow) or decreased (blue)), enabling comparison between
untreated aged, treated aged, and untreated young in the
large heat map. For instance, both the treated older samples
and the young untreated samples show increased transcript
levels in ‘‘immune response’’ and ‘‘translation,’’ as both these
groups are ‘‘up’’ (yellow). In contrast, the untreated aged
group shows decreased transcript levels, or ‘‘down’’ (blue) in
‘‘immune response’’ and ‘‘translation’’ genes compared with
the other two groups.
The gene programs associated with aging are multifaceted,
and are enriched for several biological themes. The top five
most significant GO terms that are increased in the aged
untreated compared with young untreated group included
translation (P ¼ 4.7 10
), translational elongation
(P ¼ 5.1 10
), macromolecular complex assembly (P ¼ 7.5
), ncRNA metabolic processing (P ¼ 6.2 10
and RNA processing (P ¼ 2.5 10
). The top five GO
terms that decreased in the aged untreated group
compared with the young untreated group were genes
encoding functions related to cell adhesion (P ¼ 1.5 10
), 395
ALS Chang et al.
Rejuvenation of Gene Expression in Aging Skin by BBL
biological adhesion (P ¼ 1.7 10
), homophilic cell adhe-
sion (P ¼ 7.8 10
), skeletal system development (P ¼ 3.2
), and enzyme-linked receptor protein signaling pathway
(P ¼ 5.2 10
). These gene sets are reminiscent of gene
expression changes associated with aging in other tissues and
organisms. For instance, translation-related genes or regula-
tion of translation affects aging in Caenorhabditis elegans
(Long et al., 2002) and Drosophila melanogaster (Kirby et al.,
2002). In addition, translation is believed to underlie
the important role of the TOR (target of rapamycin) pathway
in stem cell aging (Chen et al., 2009; Nelson et al., 2009;
Liu and Rando, 2011; Serrano, 2011).
BBL treatment promotes the gene expression pattern of young
Genes whose average expression level in aged treated skin
was closer to young untreated skin than aged untreated skin
were defined as RGs. Specifically, mean gene expression
levels in the treated aged group were subtracted from mean
gene expression levels in the untreated young group as well
as from the untreated aged group. If the difference in gene
expression level was less with the untreated young group
compared with the difference with the untreated aged group,
the gene was operationally defined as ‘‘rejuvenated’’. A total
of 1,293 transcripts qualified as RGs (Supplementary Table S2
online). Hierarchical clustering showed that the gene
expression pattern of treated aged skin more closely
resembled that of untreated young skin than untreated aged
skin from the same individuals (Figure 2a). The RGs reflect
coherent biological themes and include genes that fall under
the following top six most significant GO terms: translation
(P ¼ 5.8 10
), RNA processing (P ¼ 6.3 10
), ncRNA
metabolic processing (P ¼ 1.4 10
), regulation of
cellular protein metabolic process (P ¼ 1.6 10
), cellular
(n =5)
Mean score
Fine wrinkles
3.2 (1.3)
1.0 (1.0)
1.8 (2.5)
3.4 (2.3)
3.4 (1.5)
0 (0)
7.2 (1.3)
6.6 (1.1)
(n =5)
Mean score
Figure 1. Clinical and histologic effects of broadband light (BBL) treatment. (a) Arm of a 73-year old female before BBL treatment (dashed box indicates area to
be treated and bandag e indicates untreated skin). (b) The same forearm after three BBL treatments with reduced fine wrinkling, hyperpigmentation, and erythema
in the treated area (dashed box) compared with the untreated area. (c) Skin aging parameters show significant decreases in fine wrinkling, abnormal
pigmentation, and global skin aging assessment after BBL treatment. The P-value by two-sided t-test. (d) Histology of skin before BBL treatment shows elastosis
(original magnification 200, hematoxylin and eosin (H&E) stain) and (e) reduced elastosis (original magnification 200, H&E stain) after BBL treatment.
(f) Before treatment, elastosis is prominent (original magnification 200, von Giesen stain). (g) After treatment, elastosis is less distinct (original magnification
200, von Giesen stain). (h) Before treatment, collagen fibers appear attenuated and disordered (original magnification 200, periodic acid–Schiff (PAS) stain).
(i) After treatment, collagen fibers are more uniform (original magnification 200, PAS stain). Bars ¼ 1 mm each.
396 Journal of Investigative Dermatology (2013), Volume 133
ALS Chang et al.
Rejuvenation of Gene Expression in Aging Skin by BBL
macromolecular catabolic process (P ¼ 2.1 10
), and cell
cycle ( ¼ 2.4 10
; (Figure 2b, upper right).
A closer inspection of genes with expression patterns that
were ‘‘rejuvenated’’ by BBL treatment revealed several key
regulators known to control organismal aging (Figure 2c).
These include ZMPSTE24, a metalloproteinase that processes
lamin A, the gene defective in the dramatic premature aging
syndrome, Hutchinson-Guilford progeria. In addition, the
IGF1R receptor was one of the RGs identified, and this gene
product is directed linked to aging and longevity in human
beings, mice, and other model organisms (Liang et al., 2011;
Tazearslan et al., 2011), as well as in other model organisms.
Other RGs include EIF4G1 and EIF4EBP1, which are
associated with increased lifespan in C. elegans (Curran
and Ruvkun, 2007). MLL is a transcription regulator that
associates with telomeres (Caslini et al., 2009), and methy-
lates H3K4, which is required for normal lifespan in C.
elegans (Greer et al., 2010). MAP3K5 (ASK10) regulates
kinase activity in response to oxidative stress in a Klotho
aging mouse model (Hsieh et al., 2010). PSMD8 is a
proteasome component, and proteasome malfunction has
been reported to contribute to aging in human skin (Hwang
et al ., 2007). RING1 and MOV10 are in the Polycomb
pathway, which controls the lifespan of human fibroblasts
(Itahana et al., 2003). EEF2 (eukaryotic translation elongation
factor 2) is also an RG, and has been reported to associate
with age-related declines in protein synthesis in rats (Parado
et al., 1999). Finally, a number of tumor-suppressor genes
that are cell-cycle checkpoints and ensure genome integrity,
such as ING4 tumor suppressor, DAXX, and MSH2, are also
RGs. Thus, BBL treatment appears to be capable of restoring
many molecular features of youthful skin to aged human skin,
at least in the short term. Notably, we did not see gene
expression changes associated with wounding or scarring.
To confirm the findings on 3-seq, we performed quanti-
tative reverse transcription–PCR (qRT–PCR) to confirm the
Immune response
Cell adhesion
Examples of “rejuvenated” genes
with known aging function
“Rejuvenated” genes’ top 6 most
significant GO terms
RNA processing
lncRNA metabolic processing
Regulation of cellular protein
Cellular macromolecule catabolic
Cell cycle
–Log (P-value)
–2 +2-Fold
Significant genes (n =3,530) among those that change with age and with treatment
Each gene (row) in large heat map corresponds to same gene (row)
in adjacent box on right, with magenta marks indicating distributions of genes
with biologic themes.
All samples
All samples
All samples
All samples
All samples
Figure 2. Effects of broadband light (BBL) treatment on coding and noncoding RNAs in aging skin. (a) Gene expression clustering of treated aged samples is
intermediate between untreated young and untreated aged samples. Transcript levels that significantly change with untreated young versus untreated aged
samples, as well as untreated aged versus treated aged samples (n ¼ 3,530 total transcripts), are shown. Columns indicate single subject sample and rows
indicate gene. T, aged treated; U, aged untreated; Y, young untreated. Magenta columns are visual representations of the gene distributions on the large heat
map (left) as grouped by biological function. For instance, ‘‘immune response’’ and ‘‘translation’’ related genes are on the lower half of the heat map, with
yellow indicating increased levels (or ‘‘up’’) in treated aged and untreated young groups; the corresponding location in the large heat map for immune response
and translation are blue (or ‘‘down’’) in the untreated aged group. Distributions on the large heat map of rejuvenated genes (RGs; n ¼ 1,293) and ‘‘long
noncoding RNAs’’ (lncRNAs) are shown in the first and second magenta columns, respectively. (b) The top six most significant Gene Ontology (GO) terms
among RGs. (c) Examples of RGs with known aging function. 397
ALS Chang et al.
Rejuvenation of Gene Expression in Aging Skin by BBL
levels of ZMPSTE24 on an independent group of untreated
women across a spectrum of ages. The 3-seq had showed that
untreated aged skin had the highest levels of ZMPSTE24
transcript expression level, treated aged skin had intermedi-
ate levels of ZMPSTE24 transcript level, and untreated young
skin had the lowest levels (Figure 3a). By qRT–PCR, untreated
aged arm skin (age 75 years) had the highest ZMPSTE24
transcript levels, untreated middle-aged arm skin (age 35
years) had intermediate levels, and untreated young arm skin
(age 24 years) had the lowest levels (Figure 3b). This gradient
has not been reported earlier in humans, but is an
independent indicator suggesting that our findings are of
biological relevance to physiological aging.
The enrichment in mRNAs encoding genes involved in
RNA processing prompted us to evaluate the expression
levels of additional RNA classes. The lncRNAs are a newly
recognized class of genetic elements that are pervasively
transcribed in the human genome (Wang et al., 2009;
Wapinski and Chang, 2011). The roles of lncRNAs in aging
and in skin have not been studied, as they have not been
represented on microarray platforms in the past. However,
the 3-seq technology can readily capture and quantify
lncRNA expression. Of the 3,530 transcripts with altered
levels between untreated young and untreated aged, 151 are
lncRNAs. The chromosomal locations and most proximate
genes of these lncRNAs are shown in Supplementary Table
S3 online. Of the 1,293 RGs, 42 were lncRNAs. The
chromosomal locations and most proximate genes of these
lncRNAs are listed in Supplementary Table S4 online, with
heat map in Supplementary Figure S1 online. These findings
suggest that lncRNAs are potentially involved in the process
of aging and rejuvenation, paralleling their roles in develop-
ment and cellular reprogramming (Gupta et al., 2010; Loewer
et al., 2010). Our data provide an initial set of lncRNAs
associated with human aging that sets the groundwork for
functional studies in the future.
GO analysis of the 151 lncRNAs with significant
difference in expression between young untreated and aged
untreated skin showed no significant enrichment for terms.
Similarly, GO analysis of the 42 ‘‘rejuvenated’’ lncRNAs
showed no significant enrichment for terms. However, the
importance of lncRNAs in ‘‘rejuvenation’’ is not necessarily
diminished. For instance, our 42 lncRNAs are a small number
and future studies with greater sample size may identify more
lncRNAs, enabling identification of significant GO terms. In
addition, lncRNAs are a new class of RNA, and our GO
analysis relied on the proximity of lncRNA sequences to
known genes; it is possible that lncRNAs are important for
regulating genes that are not necessarily proximal to the
lncRNA (Gupta et al., 2010).
The effect of BBL treatment on the immune response
includes altering the immune profile in a way that resembles
untreated young skin. Figure 2a shows that although genes
related to immune response are ‘‘up’’ after treatment, this
‘‘up’’ profile more closely resembles untreated young samples.
This suggests that at least a portion of the immune response
that is ‘‘up’’ after treatment is part of the ‘‘rejuvenated’’ profile
and not specific to being treated with BBL.
The NF-kB pathway had been shown to be important in
skin aging and rejuvenation (Adler et al., 2007), and we
found that the RGs are indeed highly enriched for genes
bound by NF-kB as measured by chromatin immunoprecipi-
tation sequencing experiments. In all, 827 of the 1,293 RGs
are bound by NF-kB(P ¼ 1.2 10
, hypergeometric test).
Interestingly, NF-kB itself was not one of the identified RGs.
termination appears unaffected by aging or BBL
The 3-seq captures the 3
polyadenylated (polyA) RNA
fragments for deep sequencing, and thus has the potential
to detect alterations in the location of 3
transcript termina-
tion. The 3-seq method samples RNA sequences immediately
upstream of the polyA tails. If there were changes in the use
of the polyA site within the last exon such that the last exon is
lengthened or truncated, this would be detected in the
sequencing reads. This method does not evaluate the length
of the polyA tail.
Relative ZMPSTE24
Age (years):
3 RNA sequencing
150 -
150 -
150 -
150 -
150 -
150 -
chr1: 40,500,000
10 kb
OldOldYoungYoung Old+BBLOld+BBL
Middle aged
Figure 3. ZMPSTE24 transcript levels increase after broadband light (BBL)
treatment. (a) Schematic of ZMPSTE24 locus on chromosome 1, hg18. The
-seq (deep sequencing of RNA 3
end) reads were plotted for two old
individuals with and without BBL treatment and two untreated young
samples. (b) ZMPSTE24 transcript expression is lower in untreated old skin
compared with untreated young skin by quantitative reverse transcription–
PCR (RT–qPCR). ZMPSTE24 transcript expression in untreated middle-aged
skin is intermediate (n ¼ 1).
398 Journal of Investigative Dermatology (2013), Volume 133
ALS Chang et al.
Rejuvenation of Gene Expression in Aging Skin by BBL
Alternative 3
-end usage is an important regulatory
mechanism (Mayr and Bartel, 2009), and can alter gene
expression output by changing the content of the 3
untranslated region, which may then alter the repertoire of
microRNA targets or RNA-binding proteins (such as those
known to occur in cancer; Shapiro et al., 2011). Thus, in
addition to quantifying changes in transcript abundance, we
also searched for changes in transcript termination in
association with aging or BBL treatment. Systematic compar-
ison of all 3-seq reads showed that, as anticipated, the
majority of reads fell into the annotated last exon, i.e.,
o1,000 bp from the transcriptional stop site (Figure 3a), and
there were no consistent changes of 3
-end usage associated
with aging or BBL treatment (Figure 3b). For instance, if the
distribution of distances from transcriptional stop site for the
RNAs from young untreated and aged treated samples were
different, then aging may be associated with systemic
changes in mRNA 3
terminations (Figure 4).
Treatment-specific effects of BBL
In addition to affecting the age-associated gene expression
program, we also considered the possibility that BBL
treatment may induce unique treatment-specific effects that
are distinct from aging. For instance, BBL treatment could
induce wound healing or scarring response in addition to
rejuvenation effects. We identified consistent changes in the
expression of 1,112 genes that occur only in BBL-treated
samples but not in either untreated young or untreated aged
samples. Among these treatment-specific genes, the top five
GO term categories significantly associated with increased
expression after treatment were as follows: immune response
(P ¼ 3.8 10
), positive regulation of immune system
process (P ¼ 2.0 10
), cell activation (P ¼ 5.7 10
), T-
cell activation (6.0 10
), and defense response
(P ¼ 1.4 10
). These categories are suggestive of an
immune response to BBL separate from the immune response
genes that are also increased in untreated young samples (as
mentioned in the above section). The top five GO term
categories significantly associated with decreased expression
after treatment were as follows: regulation of transcription
(P ¼ 2.0 10
), transcription (P ¼ 1.7 10
), response to
organic substance (P ¼ 1.1 10
), response to hormone
stimulus (P ¼ 4.4 10
), and negative regulation of tran-
scription (P ¼ 4.7 10
). These genes are distinct from a
previously described ‘‘wound signature’’ that characterizes
response to skin wounding (Chang et al., 2005); however, it is
difficult to directly compare signatures with those in our
study, as there are no published data at the equivalent time
point after wounding as used in this study (4 weeks).
Finally, the top 10 genes that are most highly upregulated
and downregulated in the treated aged samples compared
with the untreated aged samples are listed in Table 1.
Our results suggest that regulators of organismal aging can be
altered in human skin using commonly available BBL
technology. How such plasticity in aging may be modulated
for healthful benefits such as prevention or treatment of age-
associated skin conditions remains to be seen. Although BBL
technology has been harnessed for its ability to produce a
more clinically ‘‘youthful’’ appearance, our study suggests
that ‘‘rejuvenation’’ at a molecular level has also occurred,
with a number of genes linked to the aging process being
altered in expression after treatment to more closely resemble
young skin. Hence, it is possible that the clinical phenotype
represents a functional rejuvenation (at least in the short
term), rather than just a cosmetic mimic of youthful
As the BBL technology has been in existence for o20
years, the long-term effects of BBL remain to be determined.
Although this study assessed the skin 4 weeks after treatment,
it is unclear how durable the clinical and molecular response
is. Also unknown is whether there is a decrease of age-
associated skin changes such as seborrheic keratosis or
actinic keratosis with time. It may be informative to follow
these current participants in the long term (e.g., 45 years)
with photographs and skin biopsies to determine the duration
of clinical, histologic, and molecular effect of BBL treatment.
The precise mechanisms by which BBL (noncoherent
wavelengths of light) alters gene expression are currently not
well understood. For instance, it is known that BBL is
absorbed by different targets including melanin and hemo-
globin, leading to decreased erythema and pigmentation. It is
thought that the decrease in fine wrinkling is partly due to the
production of new collagen (Fisher et al., 2008). However,
the genes identified in this study were not collagen specific. It
may be possible that if the posttreatment skin biopsies were per-
formed earlier than 4 weeks, some of the gene expression changes
related to collagen production might have been captured.
Gene expression programs associated with human aging
appear to differ between organ types. For instance, the aging
human kidney and human muscle seem to have distinct
gene expression signatures (Rodwell et al., 2004; Zahn
et al., 2006). The aging gene expression profiles of human
skin generated in this study do not appear to be the same as
Table 1. Top 10 most significantly changed gene
expression levels overall between BBL-treated aged
samples and untreated aged samples
Gene symbol
Fold change: treated aged
versus untreated aged
of change
HEPHL1 3.19 Down
ZNF660 3.09 Down
LY6G6D 2.53 Down
COCH 2.38 Down
CCL18 2.36 Up
CEP78 2.36 Down
ANGPTL7 2.34 Down
SLN 2.17 Down
CPXM1 2.10 Up
SAMD5 2.08 Down
Abbreviation: BBL, broadband light. 399
ALS Chang et al.
Rejuvenation of Gene Expression in Aging Skin by BBL
other reported organ types; however, future direct compar-
ison studies may shed more light on this issue.
NF-kB is an important regulator of gene expression in
many contexts. In this case, the most relevant role of NF-kBis
likely in controlling cell senescence (Bernard et al., 2004;
Adler et al., 2007) and immune response. Our finding that
RGs are highly enriched for NF-kB-bound genes suggests that
BBL may influence pathways controlled by NF-kB. The
precise mechanisms by which this occurs remain to be
investigated. Nevertheless, our results are consistent with a
prior study showing that inducible blockade of NF-kB in aged
murine skin restores the gene expression program and
phenotypes of young skin (Adler et al., 2007).
It is difficult to directly compare the results of our study
with the gene expression profiles in humans reported
currently in the literature for two reasons: (1) the time point
of biopsies may not be exactly the same, and (2) the nature of
the disease entity or treatment is not the same as BBL. For
instance, gene expression patterns in human postburn
hypertrophic scars at 6–15 months in two pediatric and two
adult patients identified six genes as significantly increased
(Paddock et al., 2003), none of which were significantly
changed in our BBL study. In another example, an in vitro
human keratinocyte model using scratch wounding has
shown increased activation of NF-kB in cells between
1 and 14 days (Adams et al., 2007). Our study captured the
1-month time point when the effects of wound healing might
be decreasing, and we are more likely to detect rejuvenation
effects. At our 1-month time point, NF-kB levels were not
significantly increased, but genes known to interact with
NF-kB were significantly increased, which is a distinct and,
to our knowledge, previously unreported finding.
Two RGs, RING1 and MOV10, are in the Polycomb
pathway, with the potential to contribute to both rejuvenation
effects and wound repair. In mice and cell culture, the
Polycomb pathway controls the lifespan of human fibroblasts
(Itahana et al., 2003) and associates with the upregulation of
wound repair genes (Shaw and Martin, 2009).
The ligands for Toll-like receptors 2, 3, and 5 have been
reported to affect the transcript and protein levels of matrix
metalloproteinases 1 and 9 and induce the nuclear transloca-
tion of NF-kB after 24–48 hours in human keratinocyte
culture (Lee et al., 2009). We did not detect significant
increases in Toll-like receptors 2, 3, and 5, or NF-kB, but
our study was in vivo and skin samples were obtained at the
1-month time point.
In addition, although our data show that coherent
biological themes such as ‘‘translation’’ or ‘‘RNA processing’’
are altered after BBL treatment, our study does not identify the
population of cells within the skin that undergo these changes.
Future studies that get at this question may better explain how
BBL treatment might lead to histological or structural changes
such as resorption of elastosis or collagen deposition.
Figure 4. Broadband light (BBL) treatment and aging show no systematic
changes of 3
-end usage. (a) Systematic comparison of all 3-seq (deep
sequencing of RNA 3
end) reads showing that the majority of reads fell into
the annotated last exon (based on distance of within 1,000 bp from
transcriptional start site (TSS)) for untreated aged, treated aged, and untreated
young groups. The y-axis shows the average intensity of the 3-seq signal.
(b) There were no systematic changes of 3
-end usage associated with aging or
BBL treatment, as the reads showed similar length distributions between the
untreated aged, treated aged, and untreated young groups.
Aged untreated
Distance from transcriptional stop site (kb)
Average diagram
Average intensity
Distance from TSS (bp)
Aged untreated
Aged treated
–500 0
YoungAged treated
400 Journal of Investigative Dermatology (2013), Volume 133
ALS Chang et al.
Rejuvenation of Gene Expression in Aging Skin by BBL
It would be interesting to compare whether other
modalities known to reduce clinical skin aging parameters
such as topical tretinoin result in gene expression changes
that are in common with BBL-induced changes.
In addition, comparison of non-sun-exposed older skin
before and after treatment may identify gene expression
changes that are specific to intrinsic skin aging.
This is an exploratory study, and we will consider
including treated young skin in future studies. In this study,
we did not treat younger skin (defined as age o30 years
for this study) because there was no clinical indication;
these subjects did not have detectable photoaging or intrinsic
aging on the arm skin. As it is unlikely that BBL would be used
in practice on young skin without photoaging (except possibly
for hair removal), we did not include this group in the study.
The current literature on the ability of BBL to induce
collagen neogenesis is contradictory. Although some reports
on histologic changes induced by BBL include collagen
neogenesis (Negishi et al., 2001), there are other studies
showing no change (Prieto et al., 2002). This latter study also
reported no change in elastin content after treatment. In our
study, there were no marked changes in collagen content
after treatment on periodic acid–Schiff staining. There were
decreases in the amount of elastin on von Giesen staining.
We did not detect any significant changes in collagen or
elastin gene expression levels after treatment. One possibility
is that the histology was taken at a single time point, and may
not have captured the time when collagen or elastin
expression levels were more markedly changed. Future
studies will indeed biopsy-treated skin longitudinally to
reveal the kinetics of activation/suppression of target genes.
In addition, it is precisely the goal of this study to extend
beyond the conventional histologic analysis of skin and
explore molecular changes of skin aging and BBL treatment.
We observed numerous gene expression changes related to
pathways beyond connective tissue organization that can be
modulated by BBL.
Finally, future studies with larger sample size may enable
us to identify additional significant genes (both coding and
noncoding) whose expression is altered in untreated young
versus untreated aged, as well as untreated aged and treated
aged human skin samples. Larger sample size might also
enable us to correlate the degree of clinical response with
more ‘‘rejuvenated’’ gene expression changes.
Human subjects and sample acquisition
This study was conducted in accordance with the Declaration of
Helsinki Principles. After Institutional Review Board approval and
written informed consent was obtained, five female participants over
the age of 50 years underwent BBL treatments to the left forearm.
Inclusion criteria included Fitzpatrick skin type II or III, and a global
assessment of forearm skin aging consistent with moderate or severe
forearm skin aging (modified validated instrument from McKenzie
et al., 2010) for treated participants. Treatments were performed on
the Sciton Joule Platform using the BBL module. The same investigator
performed the treatments at 4-week intervals for a total of three
treatments using a 515-nm or a 560-nm cutoff filter at a single long
pulse of 10–20ms duration, with fluences of 8–14 J cm
treatment session, two or more passes were performed. At 4 weeks
after the third BBL treatment, 4-mm skin biopsies were performed by
the Keys punch technique from the treated and adjacent untreated
skin. Punch biopsies (4 mm) were taken from non-sun-exposed arm
skin of five participants o30 years old. These specimens were
bisected and placed into either RNAlater (Ambion, cat. no. AM7022,
Grand Island, NY) or formalin solution for staining with hematoxylin
and eosin, von Giesen, or periodic acid–Schiff.
The 3-seq and bioinformatics
Total RNA was extracted using the RNeasy Fibrous Tissue Mini Kit
(Qiagen, Germantown, MD). The 3-seq was performed as described in
Beck et al. (2010). In brief, oligo-dT-directed reverse transcription
generated complementary DNAs corresponding to 3
ends of polyA
transcripts; the complementary DNAs were cloned and subjected to
deep sequencing on the Illumina GAIIx (San Diego, CA) platform with
raw read length of 36 bp. Raw reads were aligned to human genome
(hg18) using bowtie (Langmead et al., 2009); each sample generated
6.5–12.4 million uniquely mappable reads. The 3
sequencing of skin
transcripts was performed to assess length distributions.
Reads per kilobase of exon per million mappable reads (RPKM, a
direct measure of transcript abundance) and the number of raw reads
falling on to each gene were calculated using a self-developed script
by Kun Qu. The Reference Sequence (RefSeq; www.ncbi.nlm.nih.-
gov/RefSeq) and Ensembl ( annotated non-
coding genes were included. Significant genes were called using the
DESeq package ( comparing aged
treated with aged untreated samples (genes changed because of
treatment), and aged untreated with young untreated samples (genes
changed because of aging). Unsupervised hierarchical clustering of
significantly different expressed genes was performed using Cluster.
The GO terms were generated using DAVID (Database for Annotation,
Visualization and Integrated Discovery) Bioinformatics Resources 6.7
( Genes close to lncGenes were identified
using GREAT database ( These data have
been deposited into the Gene Expression Omnibus.
To determine the overlap between RGs and NF-kB binding, we
downloaded the NF-kB-bound genes identified by the ENCODE
project (ENCODE Consortium, 2011) by chromatin immunopreci-
pitation sequencing experiments. A total of 9,650 genes bound NF-
kB in one or more cell types, and these were compared with the RG
gene list.
Total RNA was extracted with TRIzol (Invitrogen, Grand Island, NY)
followed by RNeasy column purification (Qiagen) and DNAse
Turbo Treatment (Ambion). RT–qPCR was performed using total
RNA (10 ng), Taqman One Step RT–PCR master mix, and one
of the following Taqman assays: GAPDH (Hs99999905_m1) and
ZMPSTE24 (Hs00956778_m1; Applied Biosystems, Carlsbad, CA).
Reactions were in triplicate for each sample and were performed a
minimum of two times. Data were normalized to glyceraldehyde-3-
phosphate dehydrogenase (GAPDH) levels.
PB has given lectures on broadband light technology. The other authors state
no conflict of interest. 401
ALS Chang et al.
Rejuvenation of Gene Expression in Aging Skin by BBL
This study was funded by a research grant from Sciton. We are indebted to
Paul Khavari and Jean Tang for prereview of the manuscript. We thank Olena
Mykhaylichenko and Sarah Jacobs for administrative support.
Supplementary material is linked to the online version of the paper at http://
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402 Journal of Investigative Dermatology (2013), Volume 133
ALS Chang et al.
Rejuvenation of Gene Expression in Aging Skin by BBL

Supplementary resource (1)

... Research by broadband light has focused on a rather limited examination of gene expression, isolating specific genes and emphasizing the aspects that fit their rejuvenation hypotheses, while neglecting the potential harmful effects that overexpression of these same genes may present. [31][32] The researchers are affiliated with Stanford University, however, research cited was financed by Sciton, a company producing medical and aesthetic laser technologies, the Nu Skin multilevel marketing company and others. Initially, these investigators did not actually test facial skin but took biopsies from the forearms of healthy older females with moderate to severe photodamage on their forearms. ...
The reality of interacting genes and proteins is vastly complex and intricate with many unknowns which currently prevent us from solving the anti-ageing equation in terms of gene expression. Molecular studies involving genome modification should take into consideration the importance of apparently opposing genes and proteins which when seen as a whole, can orchestrate an optimal systemic balance. Gene expression is often a double-edged sword with positive effects turning negative when a particular gene is overexpressed. For this reason, the US National Academy of Sciences and the National Academy of Medicine have placed stringent restrictions on the promising genome editing methods to be used only for the specific DNA sequence associated with a transmissible genetic disease. Rejuvenation as a result of gene expression is still an open area of research with studies that have either been limited to in vitro research or clinical studies claiming success based on a limited perspective that selectively emphasises the benefits of certain genes while leaving the negative outcomes in the shadows of their silence. For example, some investigators relate the presence of ZMPSTE24, IGF1R, NGF4, EEF2, EIF4FBP1 CCL18, and other genes with “rejuvenation,” selectively focusing on potential benefits while ignoring the involvement of some of these genes in malignancies and inflammation. Well-controlled gene expression molecular experimental studies with mechanotherapy and effortless exercise have limited themselves to the observation of increased slow skeletal genes associated with muscle growth that do not present any adverse side effects. Overall, exercise and nutrition are still the safest and most ethical methods of gene expression at least until genome editing can be extended to delaying ageing, in the near or distant future. As observed in the research analysing gene expression as the result of different types of exercise, inflammatory events are counterbalanced by antagonizing anti-inflammatory ones. This signifies optimal biological homeostasis because health depends on the harmonious interaction of opposite processes levelling and stabilizing each other. Exercise modalities and lifestyle are still representing the cornerstone of delaying ageing and the most riskless method of increasing longevity by triggering processes that balance each other.
... The wavelength is 500-1200 nm, which can be absorbed by a variety of target color bases.36 The Broadband Light is the sixth-generation photonic technology of Profile Super Platform developed by Sciton (USA).39 The wavelength, cooling system, and energy output mode are optimized based on IPL. ...
Full-text available
Objective: To investigate the efficacy and safety of broadband light (BBL) combined with intradermal injection of tranexamic acid for treating melasma. Methods: 120 women with melasma admitted to our hospital from January 2021 to April 2022 were randomly categorized into the following groups: control group, treated with 250 mg tranexamic acid given orally twice daily, except during menstruation; group I, treated with BBL (Sciton, Inc., USA) monthly; group II, received intradermal injections of tranexamic acid monthly; and group III, treated with BBL with intradermal injection of tranexamic acid monthly. Treatment in each group lasted three months. The MASI (Melasma Area Severity Index) and VISIA (Canfield VISIA Complexion Analysis) were used for evaluation. Results: After treatment course, MASI scores and VISIA brown spot and red zone ranking improved in all four groups (p < 0.05). The decrease in MASI scores and improvement rates of VISIA brown spot and red zone rankings were not significantly different among the control group, group I, and group II; however, the decreased MASI scores and improvement rates of VISIA brown spot and red zone rankings were significantly higher in group III than in the other three groups (p < 0.05). Conclusion: The effect of BBL combined with the intradermal injection of TA in the treatment of melasma is remarkable. This combination therapy can be an alternative and effective treatment for managing melasma.
... Transcriptomic analysis comparing samples from young and aged skin has not revealed any significant differences in the protein expression of almost all proteasome subunits with the exception of PSMD8 subunit, which encodes the Rpn12 lid subunit. PSMD8 was found reduced by almost 30% in aged skin [223,224]. In contrast, Imbert and colleagues stated that proteasome activation by a dimerized tripeptide led to the reduction of the UVB-induced protein carbonylation and improvement of the senescent morphology of aged keratinocytes in vitro and in skin biopsies [222]. ...
Full-text available
The ubiquitin-proteasome system (UPS) is a key player in the maintenance of cellular protein homeostasis (proteostasis). Since proteasome function declines upon aging leading to the acceleration of its progression and the manifestation of age-related pathologies, many attempts have been performed towards proteasome activation as a strategy to promote healthspan and longevity. The marine environment hosts a plethora of organisms that produce a vast array of primary and secondary metabolites, the majority of which are unique, exhibiting a wide spectrum of biological activities. The fact that these biologically important compounds are also present in edible marine organisms has sparked the interest for elucidating their potential health-related applications. In this review, we focus on the antioxidant, anti-aging, anti-aggregation and anti-photoaging properties of various marine constituents. We further discuss representatives of marine compounds classes with regard to their potential (direct or indirect) action on UPS components that could serve as UPS modulators and exert beneficial effects on conditions such as oxidative stress, aging and age-related diseases.
... BBL has a reputation of being a high-quality IPL device that is well-established in its treatment of rosacea, hyperpigmentation, and maintenance of the youthfulness of skin. 20 This novel technique of treating both the upper and lower eyelids is now an off-label adaptation for treatment of ocular rosacea (a form of MGD DED). 21 The upper eyelids have more meibomian glands than the lower eyelids, and thus, we examined the safety of adding BBL treatment to the upper eyelids to the more standard cheek-and nose-only treatment. ...
Objective: We evaluated the safety and efficacy of an augmented BroadBand Light (BBL™) protocol on the upper and lower eyelids in improving meibomian gland dysfunction (MGD) and/or dry eye disease (DED). Background: DED, often associated with MGD, can cause significant morbidity and accounts for 3.54 billion U.S. dollars of health care spending yearly. Intense pulsed light (IPL) has been used to treat MGD DED with some success. BBL therapy, a high-quality IPL machine, shows much promise for decreasing inflammation and redness in rosacea, as well as hyperpigmentation from sun damage. Methods: A retrospective medical chart review was performed for MGD DED and/or hyperpigmentation patients who received BBL therapy between January 1, 2015, and February 28, 2020. Inclusion criteria included patients who underwent at least one BBL treatment. Each treatment involved the upper and lower eyelids, as well as cheeks, nose, and face. Each MGD DED subject completed the Ocular Surface Disease Index (OSDI) and underwent pre- and post-treatment standard clinical examinations. Results: Forty-seven patients had treatment without significant adverse effects; all patients with MGD DED reported improvement in their dry eye or blepharitis. BBL was determined to be a safe and effective treatment. There were no changes in visual acuity (p = 0.555) and OSDI scores were improved (p = 0.016). There was one case each of mild corneal/conjunctival abrasion, temporary hyperpigmentation, and two of temporary eyelash thinning. Patients with MGD also showed significant improvement in blepharitis and reduced hordeolum frequency after BBL treatment. Conclusions: This novel IPL/BBL protocol appears safe and effective for treating dry eye and blepharitis.
... In a similar study with 26 subjects, 6 months after five monthly treatments, there was a significant increase in collagen and elastic fibers [21]. In a pilot study published in 2013, the impact of IPL (BBL; Sciton Inc., Palo Alto, CA) on gene expression was explored [22]. In that study, skin aging was shown to be associated with altered expression of 2,265 RNAs, of which a little more than half became "rejuvenated" (expression levels became more similar to those in youthful skin) after treatment. ...
Full-text available
Background and Objectives Senile purpura is a common condition characterized by recurrent ecchymoses in the elderly on the extensor surfaces of the forearms, hands, and legs. Our objective is to assess the efficacy and safety of a protocol using intense pulsed light (BBL; Sciton Inc., Palo Alto, CA) to improve the appearance of senile purpura on subjects' extensor forearms. Study Design/Materials and Methods Five subjects over 65 years of age, with ecchymotic lesions measuring over 1 cm on each forearm and five younger subjects under 35 years of age, without any ecchymotic lesions, were included in the study. The subjects were treated on one randomized forearm with a new intense pulsed light protocol for four weekly sessions. Photographs and subject questionnaires were taken weekly before each treatment as well as 1 month after all treatments. Skin biopsies were taken 1 day after the last of four weekly treatments. Histological analysis, including hematoxylin and eosin, elastic van Gieson, and Masson's Trichrome staining, were carried out to assess both the epidermal thickness and dermal connective tissue structure. The protocol consists of multiple passes using an intense pulsed light (BBL; Sciton Inc.) device in which the wavelength, filter, and fluence are adjusted for each step. Step 1 uses infrared light (800–1,400 nm), high intensity, a smooth adapter, and a constant motion technique. Step 2 employs a 590‐nm filter with two different fluences and step 3 utilizes a 560‐nm filter. The fluence of steps 2–3 is increased by 1 J each treatment if no side effects are noted. Results Using a new intense pulsed light protocol in subjects with senile purpura, both the number and square area of ecchymoses on the treated arm were significantly reduced (P = 0.02 and P = 0.04, respectively, paired t test) as compared with the untreated arm at 1 month after four weekly treatments. Despite this pilot study including challenging cases of subjects on both inhaled and injected corticosteroids and blood thinners, all subjects with senile purpura had at least a 50% reduction in the total square area of their ecchymoses on their treated arm. There were no significant or long‐lasting side effects, and all subjects reported satisfaction with the treatment with a desire to continue treatments on their control arm. Blinded evaluators were able to select 100% of the time in the subjects with senile purpura, which was the treated arm as compared with the control arm when reviewing photographs from 1 month after the last treatment. In addition, several subjects were noted to have a significant improvement in the appearance of hemosiderin deposition and photodamage. Histologically, intense pulsed light treatments significantly increased epidermal thickness in elderly subjects by 21.14% (P = 0.0153, two‐tailed, paired t test), to levels comparable with young subjects. Such restoration is consistent with the other histological observations by blinded evaluators of more abundant and organized collagen fibers in the dermis and reduced aggregates of disorganized elastin fibers. Conclusion This new intense pulsed light protocol is safe and effective in improving the clinical appearance of senile purpura as well as preventing future lesions by improving the structure of the skin by increasing epidermal thickness and improving collagen and elastic fiber morphology. The treatment was well‐tolerated, adverse effects were minimal, and there was high patient satisfaction. Lasers Surg. Med. 2020. © 2020 Wiley Periodicals LLC
Skin and cellular aging are impacted by various toxins in our environment such as air pollution, water contamination, an increased prevalence of light-emitting diodes, electromagnetic frequencies, various yeast and other fungi, parasitic infections, and mold and heavy metal toxicity. Basic topical skin care is insufficient to adequately protect an individual's integumentary system and other organs from these types of daily cellular stressors. These stressors impact the level of oxidative stressstatus (OSS). OSS is measurable through biomarker analysis of various body fluids including blood, saliva, urine, and breath. This poses a unique assessment challenge for aesthetic practitioners as the OSS of a patient impacts their overall aging process. Aesthetic practitioners observe the aging process through visual assessment of a patient's skin quality, skin barrier function, and the presence of solar lentigines, erythema, edema, telangiectasia, loss of collagen and elastin, bone density, and redistribution of subcutaneous tissue. Mitigating a patient's daily exposure to OS and its impacts on the skin, other organ tissues, and metabolism poses a unique challenge in medical aesthetic treatment planning. For this reason, the use of stem cells and exosomes is gaining popularity in aesthetic medicine. The purpose of this literature review is to highlight currently available research, applications, limitations, and mitigation strategies in reducing OSS on the integumentary system and aging processes.
Skin disorders are a large family of various complex diseases and dysfunctions. With the development of epigenetics in human diseases, more and more skin disorders were proved to be associated with epigenetic modifications. Defined as heritable changes in gene expression that do not involve a change in the genomic DNA sequence, epigenetics may play a significant role and open a new window in skin disorders. In this chapter, we summarize the epigenetic modifications of a number of skin disorders, including immunologic skin diseases, infectious skin diseases, skin tumors, and skin aging. We also review a number of candidate epigenetic markers and potential therapeutic strategies. Understanding the concepts of epigenetics can provide insights into the pathogenesis of skin disorders, and may lead to the development of biomarkers, improve prognosis, and support the development of novel molecular targets in therapies, especially refractory skin diseases. Epigenetics will serve as the next large area of medicine with the potential to treat and possibly prevent skin diseases in the future.
From the introduction of pulsed light broad‐spectrum energy in 1995, intense pulsed light (IPL) has evolved to become an extremely popular and well‐accepted technology for rejuvenation of photodamaged skin in dermatology and plastic surgery practices as well as medical spas. This paper details where IPL is now, 25 years later, and discusses the wide variety of valuable uses for IPL in medical practices as well as the reasons for IPL's growth in popularity and usefulness.
Background The wide wavelength spectrum of intense pulsed light (IPL) provides an opportunity for a versatile array of clinical applications in dermatology. Methods Key randomized clinical trials which took place in the past 20 years were summarized, focusing on skin rejuvenation, including pigmented and vascular lesions. We searched Pubmed using the key words intense, pulsed, light, and skin, then filtered results for randomized clinical trials. Results and Conclusions Studies uniformly showed improvement in pigmented and vascular lesions with IPL. Efficacy in treating rhytides was only observed in some studies. IPL was also effective as a light source in treating actinic keratosis with photodynamic therapy. Rare cases of post‐inflammatory hyperpigmentation were observed.
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We analyzed expression of 81 normal muscle samples from humans of varying ages, and have identified a molecular profile for aging consisting of 250 age-regulated genes. This molecular profile correlates not only with chronological age but also with a measure of physiological age. We compared the transcriptional profile of muscle aging to previous transcriptional profiles of aging in the kidney and the brain, and found a common signature for aging in these diverse human tissues. The common aging signature consists of six genetic pathways; four pathways increase expression with age (genes in the extracellular matrix, genes involved in cell growth, genes encoding factors involved in complement activation, and genes encoding components of the cytosolic ribosome), while two pathways decrease expression with age (genes involved in chloride transport and genes encoding subunits of the mitochondrial electron transport chain). We also compared transcriptional profiles of aging in humans to those of the mouse and fly, and found that the electron transport chain pathway decreases expression with age in all three organisms, suggesting that this may be a public marker for aging across species.
BACKGROUND: Dermabrasion and deep chemical peeling are used in the treatment of photoaged skin. These ablative procedures are effective enough to produce a certain improvement but have often caused postinflammatory hyperpigmentation among Asian patients. To avoid such adverse effects, a new, nonablative procedure has been sought. OBJECTIVE: To determine the effectiveness of photorejuvenation for Asian skin using intense pulsed light (IPL). The specific parameters used, improvement ratios, side-effects, and downtime required are also discussed. METHODS: Ninety-seven patients were treated for photoaging using IPL. The cutoff filters of 550 nm and 570 nm were utilized for three to six treatments at intervals of 2 to 3 weeks. RESULTS: Treatment results were evaluated and rated by both patients and physicians at the end of the third treatment based on improvement in pigmentation, telangiectasia, and skin texture. A combined rating of “good” or “excellent” was given to more than 90% of the patients for pigmentation, more than 83% for telangiectasia, and more than 65% for skin texture. There were some minor complications in four cases: one had erythema that continued to the next day and three had minor blisters leaving no marks. CONCLUSION: Photorejuvenation using IPL is a completely safe and effective procedure even for Asian skin. It will be increasingly used for skin rejuvenation in the future.
Background and Objective New, non-ablative methods can be used in skin rejuvenation. Histologic analysis of non-ablative IPL effects on facial, sun-damaged skin.Study Design/Materials and Methods Five female subjects, wrinkle class I or II and Fitzpatrick skin types I, II, and III. IPL treatment: once monthly, 560-nm cut-off filters, spot size 8×35 mm, 28–36 J/cm. Routine histology or electron microscopy on 2-mm punches, before treatment and then 1 week, 3 months, and 12 months.ResultsPre-treatment specimens contained solar elastosis and perifollicular lymphoid infiltrates. Collagen and elastic fibers appeared unaffected by treatment. At 1-week, Demodex organisms appeared coagulated.Conclusions Under these conditions, IPL induces minimal morphologic changes in mildly sun-damaged skin. Some esthetic improvement may be secondary to clearing of Demodex organisms and reduction of associated lymphocytic infiltrate. Lasers Surg. Med. 30:82–85, 2002. © 2002 Wiley-Liss, Inc.
Background: Dermabrasion and deep chemical peeling are used in the treatment of photoaged skin. These ablative procedures are effective enough to produce a certain improvement but have often caused postinflammatory hyperpigmentation among Asian patients. To avoid such adverse effects, a new, nonablative procedure has been sought. Objective: To determine the effectiveness of photorejuvenation for Asian skin using intense pulsed light (IPL). The specific parameters used, improvement ratios, side-effects, and downtime required are also discussed. Methods: Ninety-seven patients were treated for photoaging using IPL. The cutoff filters of 550 nm and 570 nm were utilized for three to six treatments at intervals of 2 to 3 weeks. Results: Treatment results were evaluated and rated by both patients and physicians at the end of the third treatment based on improvement in pigmentation, telangiectasia, and skin texture. A combined rating of "good" or "excellent" was given to more than 90% of the patients for pigmentation, more than 83% for telangiectasia, and more than 65% for skin texture. There were some minor complications in four cases: one had erythema that continued to the next day and three had minor blisters leaving no marks. Conclusion: Photorejuvenation using IPL is a completely safe and effective procedure even for Asian skin. It will be increasingly used for skin rejuvenation in the future.
Background: Photodamaged skin is characterized not only by rhytides, but also by epidermal and dermal atrophy, rough skin texture, irregular pigmentation, telangiectasias, laxity, and enlarged pores. There is growing interest in the development of noninvasive methods to treat photodamaged skin. Skin photorejuvenation is the visible improvement of photodamaged skin using a laser or other light source. A noncoherent, broadband, pulsed light source is effective in the treatment of vascular and pigmented lesions of the skin. This study evaluates the role of intense pulsed light in the rejuvenation of photo aged skin. Objective: The purpose of this study was to evaluate and quantify the degree of visible improvement in photodamaged skin following a series of full-face, intense pulsed light treatments. Methods: Forty-nine subjects with varying degrees of photo-damage were treated with a series of four or more full-face treatments at 3-week intervals using a nonablative, nonlaser intense pulsed visible light source. Fluences varied from 30 to 50 J/cm2. Subject evaluation and skin biopsies were used to assess treatment results. Results: All aspects of photodamage including wrinkling, skin coarseness, irregular pigmentation, pore size, and telangiectasias showed visible improvement in more than 90% of subjects with minimal downtime and no scarring. Eighty-eight percent of subjects were satisfied with the overall results of their treatments. Conclusion: Treatment of photodamaged facial skin using a series of full-face treatments with intense pulsed light is a new and effective noninvasive method of skin rejuvenation with minimal risk and no patient downtime.