Aging Voice

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Preface

The World Health Organization (WHO) defines societies with a rate of aging of
more than 14%, representing the proportion of elderly people ≥65 years old as a
percentage of the total population, as “aging societies.” Many developed countries
around the world currently have a rate of aging that exceeds 14%. Japan has a par-
ticularly high rate of aging, at 26.7%, and is the first super-aged society in the
world. Furthermore, this percentage of elderly people is increasing annually.
Traditionally, elderly individuals were the ones who received care, but in a super-
aged society, the elderly have no choice but to help contribute to society.
Consequently, elderly individuals must be physically and mentally healthy.
Even in today’s internet-based society, speaking remains the most important
means of communication. Functional decline in phonation greatly damage the qual-
ity of life of elderly individuals. Confronted with an aging society, Japanese experts
in laryngology, logopedics, and phoniatrics have been conducting research into the
aging of the phonatory function from various perspectives. Japan is already ahead
of the world with regard to regenerative medicine. This book covers the processes
of experts in their respective fields, from identifying the changes and features of
laryngeal and phonatory function associated with aging, to the development of
treatments, including regenerative medicine. In addition to speech–language–hear-
ing therapists, who provide voice therapy, this book discusses how physicians spe-
cializing in fields such as otorhinolaryngology, laryngology, logopedics, and
phoniatrics could become crucial to elderly individuals struggling with age-related
changes to phonatory function. We hope that this book will contribute to improving
voice-related quality of life for the elderly.

Tokyo, Japan Kiyoshi Makiyama

Kyoto, Japan Shigeru Hirano

v
Acknowledgments

This book was edited in collaboration with Professor Shigeru Hirano of Kyoto
Prefectural University of Medicine. Professor Hirano was of great assistance, and
editing this book would not have been possible without his input. I am deeply grate-
ful to him, and to the other authors, who have made great efforts to ensure that this
book is most useful and educational to readers in all the fields concerned.
Professors Emeritus Masayuki Sawashima and Hajime Hirose from the
University of Tokyo, Japan, and Professors Emeritus Charles N Ford and Diane M
Bless from the University of Wisconsin, USA, also spent time teaching me about the
basics of laryngology, logopedics, and phoniatrics. The knowledge I learned from
them became the foundation for this book, and I am also deeply grateful to them.
Finally, and most importantly, I wish to thank my wife, Yukari Makiyama, MD,
for her dedicated support during my work on this book.
Kiyoshi Makiyama

I am most grateful to Professor Kiyoshi Makiyama for his proposal management,

and for the editing of this distinguished book on vocal aging. The contents of the
book are fascinating and most informative owing to the maximum efforts of every
author involved, which are most appreciated.
I also express my cordial gratitude to Professor Shin-ichi Kanemaru for his
invaluable and indispensable cooperation and advice for more than 15 years in
research on tissue engineering and regenerative medicine.
Finally, I thank my wife, Chika Hirano, for her continuous and dedicated
support.
Shigeru Hirano

vii
Contents

1 Overview ������������������������������������������������������������������������������������������������������ 1
Shigeru Hirano
2 Age-Related Histological Changes of the Vocal Folds������������������������������ 9
Masanobu Mizuta
3 Age-Related Changes in the Human Voice���������������������������������������������� 27
Hideki Kasuya and Hajime Yoshida
4 Evaluation of Phonatory Function in the Elderly���������������������������������� 37
Hiroumi Matsuzaki and Kiyoshi Makiyama
5 Clinical Assessment of Elderly Vocal Folds by Laryngoscopy �������������� 45
Yoichiro Sugiyama
6 Quantitative Analysis of High-Speed Digital Imaging
for the Elderly�������������������������������������������������������������������������������������������� 53
Akihito Yamauchi and Niro Tayama
7 Collagen Injection for the Elderly with Dysphonia�������������������������������� 67
Hiroumi Matsuzaki and Kiyoshi Makiyama
8 Fat Injection for Voice Improvement in Atrophic Vocal Folds�������������� 75
Etsuyo Tamura
9 Voice Therapy for the Elderly������������������������������������������������������������������ 83
Mami Kaneko
10 Current Topics in Regenerative Medicine
for the Laryngeal Tissues�������������������������������������������������������������������������� 95
Yo Kishimoto
11 Future Prospects�������������������������������������������������������������������������������������� 109
Shigeru Hirano and Shin-ichi Kanemaru

ix
Chapter 1
Overview

Shigeru Hirano

Abstract Aging affects whole organs of the body, and the vocal fold is no excep-
tion. Voice is produced chiefly from the combined activity of respiration, vocal fold
vibration, and resonance. With age, all elements related to voice production deterio-
rate, and the mechanism of an aged voice is complex. Respiratory power is reduced,
the vocal fold function is decreased, and the motor function of resonant organs such
as the palate, lip, and tongue is weakened. The vocal fold often becomes thin and
weak, which causes atrophy of the vocal fold. The vibration of the vocal fold is
weakened with glottal insufficiency, and the voice becomes harsh, breathy, and
weak. Control of vocal organs by the central nervous system can also be affected by
aging. Treatment of an aging voice is difficult. Voice therapy consisting of respira-
tory training and vocal function exercise help to improve the voice in mild cases of
dysphonia. Injection laryngoplasty or medialization thyroplasty is applied to reduce
the glottal gap by augmentation of the vocal folds, but the effects are limited because
the vibratory properties of the vocal folds are rarely improved. Recently, a regenera-
tive approach has been attempted, to revive the vocal fold mucosa using basic fibro-
blast growth factor, which stimulates growth of fibroblasts in the vocal fold and
modulates the function. Further research is warranted to improve therapeutic tools
for age-related voice problems.

1.1 Introduction

There is a shift toward an older population affecting demographics around the

world. Japan is one of the most typical countries where aging of the population is
taking place. The number of people older than 65 years comprised 25% of the total
population in Japan in 2015, and is expected to increase to 33% of the total popula-
tion by 2035. It is 14.7% in America, but the number of people who will turn 65 over
the next two decades is expected to increase by one third, and will reach 72 million
in 2030 from 35 million in 2003 [1]. This population shift is thus a universal

S. Hirano
Department of Otolaryngology Head and Neck Surgery,
Kyoto Prefectural University of Medicine, Kyoto, Japan
e-mail: hirano@koto.kpu-m.ac.jp

© Springer Nature Singapore Pte Ltd. 2017 1

K. Makiyama, S. Hirano (eds.), Aging Voice,
DOI 10.1007/978-981-10-3698-9_1
2 S. Hirano

phenomenon, and causes several issues, including health care cost, pension, socio-
economic conflict between generations, etc. Health care expense may be the most
considerable nationwide problem that can threaten the national treasury. It is impor-
tant to fully understand the mechanism of aging, and to explore measure for anti-­
aging, healthy aging, or preemptive medicine.

1.2 Aging Mechanism

Human beings necessarily encounter aging. It is believed that the human peaks at
30 years of age, and then declines 1% per year in not only physiological aspects, but
also psychological and sociological aspects. Age-related changes occur in any part
of the body, including neurological, respiratory, cardiovascular, gastrointestinal,
immunological, endocrine, muscular, skeletal, and dermal systems (Table 1.1).
Structural and histological deterioration leads to functional deficit, and aging also
affects the communicative organs or function, with manifestation of hearing loss,
visual impairment, and voice problems.
The biological basis of aging is not fully elucidated, but two main theories are
advocated: program-related aging and damage-/error-related aging. Telomere short-
ening theory is the representative of programmed aging. Telomere is a section of
DNA found at the end of each chromosome, consists of the same repeated sequence
of bases, e.g., TTAGGG in humans. Telomere protects the chromosome, allows
replication of the chromosome during cell division, and with each cell replication,
the telomere length is shortened. The length of the telomere is defined genetically,
which determines the lifespan of the organism. The telomere is referred to as the
molecular clock marker.
The damage-related theory explains aging as the damage or mutation of DNA
causing abnormal gene expression that leads to structural and functional deteriora-
tion of organs and several diseases, including cancer. Each cell division provides a
chance of error in DNA replication, and thus environmental aspects such as ­smoking,
alcohol, diet, etc., are important in this theory. DNA can be degraded over time by
environmental factors, which leads to the progressive dysfunction of organs

Table 1.1 Representatives System Disorders

of age-related disorder
Cardiovascular Atherosclerosis, hypertension,
ischemic heart disease
Respiratory Chronic obstructive pulmonary disease
Neurological Dementia, motor neuron disease
Parkinson’s disease, multiple sclerosis
Gastrointestinal Atrophic gastritis, constipation
Immune Infectious disease, autoimmune disease
Endocrine Diabetes
Musculoskeletal Rheumatoid arthritis, osteoporosis
1 Overview 3

a­ ssociated with aging. Free radical or oxidative stress is another strong element that
damages DNA and allows the aging mechanism to proceed.
Aging effects can differ according to individuals, gender, races or even each
organ. Females have a longer lifespan than males. The progression of aging differs
individually, and can be caused by genetic factors. Therefore, physiological age is
often different or variable from chronological age. Organs with frequent cell repli-
cation or those that are renewable may have more chance of telomere shortening
and/or error in DNA replication in such cases of skin, bone, blood, and connective
tissues. Organs with less cell replication, such as neural and muscular systems, can
accumulate damaged DNA, which leads to organ dysfunction with age, such as
dementia, neurological disorder, and locomotive syndrome. Aging has complexity.

1.3 Mechanism of Voicing

The production of voice is intriguing (Fig. 1.1). Sufficient expiratory flow is neces-
sary to drive the vibration of the vocal fold. The vocal fold consists of paired mucosa
that separate during respiration, and close up during voicing. Proper vibration
requires complete glottal closure. The vocal folds begin to vibrate when sufficient
subglottal pressure is provided (Fig. 1.2). The vocal folds vibrate at approximately
100 cycles per second in men, and 200 cycles per second in women. This fundamen-
tal cycle determines the pitch of the voice.

Voice Vocal tract

Resonant sound
Vocal fold
Glottal source sound
Airflow

Fig. 1.1 Mechanism of voicing

4 S. Hirano

Fig. 1.2 Vocal fold vibration

The sounds generated by vocal fold vibrations consist of a fundamental

f­requency and its harmonics, and this sound is a kind of monotone buzz. The
sound is then modified in the vocal tract until it is finally emitted from the lips.
This modification in the vocal tract is called resonance, and the resonance deter-
mines the voice quality, which is distinguishable for each individual. The vocal
tract consists of the pharynx, oral cavity, and nasal cavity. As the glottic sounds
pass through the vocal tract, some frequencies are weakened and others are
enhanced, and this mechanism finally produces four or five important resonance
frequencies called formants.
The production of voice requires at least airflow, vocal fold vibration, and reso-
nance. Aging affects the whole mechanism, which leads to presbyphonia.

1.4 Aging Voice: Complex Aspects

Aging takes place in any tissues and organs, and the vocal system is no exception.
The vocal system primarily consists of the respiratory, vibratory, and resonant
organs as described above, but also involves the whole body, spirit, and central ner-
vous system. Herein, the aging voice has some complex aspects.

1.4.1 Perceptual and Acoustic Aspect

Age-related voice problems have been reported in 10–47% of elderly people over
65 years of age [2–4]. The voice usually becomes weak, breathy, harsh, or thin.
Phonatory duration is shortened, and the pitch changes. Men’s voices tend to
become higher, and women’s voices become lower, but individual variations are
wide. Hormonal change also affects the pitch, particularly in women’s voices. These
voice changes can reduce speech intelligibility, which then causes a negative impact
on the quality of life.
1 Overview 5

Fig. 1.3 Vocal fold atrophy with age. Vocal fold bowing and glottal insufficiency are noted

1.4.2 Structural and Histological Aspect

In general, the vocal fold becomes thin and tense with age, which leads to atrophy
of the vocal fold mucosa (Fig. 1.3). The atrophy was reported to be more frequent
in males (approximately 70%) than in females (approximately 30%) [5]. The atro-
phy causes glottal incompetence during phonation and reduction of mucosal wave
amplitude and dynamics of the vocal fold.
Histological changes are the most critical aspect of this structural change. Normal
vocal fold has a layered structure where three layers with different viscoelasticity
are aligned. Hyaluronic acid is one of the key elements inside the mucosa to main-
tain the optimal tissue property of the vocal fold as a vibratory organ. With age,
hyaluronic acid decreases, and a reduced turnover of other extracellular matrix
causes atrophy with increased stiffness.
Thyroarytenoid muscle (TA), one of the intralaryngeal muscles, plays an impor-
tant role to maintain the rigidity of the vocal fold body on which pliable mucosa
vibrates. The contraction of the TA muscle is necessary to create regular, stable
sounds, but aging effects cause atrophy of the TA, which leads to unstable, disturbed
mucosal vibration. Atrophy of the TA also causes incompetence of glottal closure.
Hydration of the vocal fold mucosa is another important element for consistent
vibration. Dry mucosa has difficulty vibrating. Hydration is maintained by serous
secretion by the laryngeal glands, but aging also affects the secretion. Reduction of
secretion with age causes dehydration of the vocal fold and disturbs vibration.

1.4.3 Functional Aspect: Pulmonary, Vibratory, Resonant

Pulmonary function declines with age, possibly accompanied by other comorbidi-

ties. Poor pulmonary reserve can affect subglottal pressure, duration of phonation,
pitch, and loudness of the voice. Postural deterioration such as kyphosis in elderly
persons can also compromise pulmonary function and lead to voice changes.
6 S. Hirano

The vibratory function of the vocal fold is decreased as mentioned above by the
reduction of mucosal wave amplitude and glottal incompetence.
The function of resonant organs also declines with age. The movements of the
soft palate, tongue, and lip become slow and clumsy. The structure of the vocal tract
is changed because of the descent of the larynx, and the increase in length and vol-
ume of the oral cavity. Secretions through the vocal tract decrease and become
thick. These organic and functional changes alter the resonance of the voice, which
usually leads to a poor voice.

1.4.4 Neurological Aspect

There are several central nervous system (CNS) pathological conditions observed in
elderly subjects that may influence the voice, including stroke, tremor, Parkinson’s
disease, or other degenerative diseases.
Motor neuron diseases can affect the voice. Upper motor neuron disease
causes spastic disorder or myoclonus of the larynx, which leads to severe dys-
phonia. Lower neuron disease presents with paralysis and muscle atrophy of the
vocal fold, which causes vocal fold bowing with glottal insufficiency.
Amyotrophic lateral sclerosis is one of most common mixed motor neuron dis-
eases that affect voice, swallowing, and articulation. The voice usually becomes
weak and breathy.
Multiple sclerosis (MS) is a neurodegenerative disease with multiple lesions of
the white matter of the brain. MS causes various symptoms in the whole body, in
addition to voice tremor, spasm, and dysphagia.
Extrapyramidal diseases include Parkinson’s disease, spasmodic dysphonia, and
essential tremor. Parkinson’s disease is common in the USA, and is derived from the
degeneration of dopamine-producing cells of the substantia nigra in the brainstem.
The disease causes tremor, rigidity in the whole body, and leads to a weak and
breathy voice due to glottal insufficiency and poor respiratory support in more than
70% of patients.

1.4.5 Genetic Aspect

Although most elderly people demonstrate some change of voice with structural
changes of the vocal fold, the degree of dysphonia varies individually. Individual
genetic differences are assumed. It is well known that gene expression of the
extracellular matrix in the vocal fold changes with age, which leads to structural
and histological deterioration of the vocal fold. On the other hand, it was
reported that telomere length in the vocal fold did not change significantly with
age [6].
1 Overview 7

Table 1.2 Treatment of Voice therapy Vocal function exercise

vocal fold atrophy with age
Injection laryngoplasty
Framework surgery Medialization thyroplasty
Regenerative medicine Basic fibroblast growth factor

1.5 Treatment of Aging Voice

Given the complex aspects of an aged voice, the treatment is often difficult. Voice
therapy addresses the respiratory and phonatory functions. Strengthening of respira-
tory support and phonatory control can increase neuromuscular coordination. Voice
therapy consists of education about phonatory physiology, the practice of respira-
tion and resonance, and vocal function exercise [7]. Voice therapy can contribute to
improvement of the aged voice, but the effects are often limited, and possibly few
for severe cases (Table 1.2).
Injection laryngoplasty and medialization framework surgery are performed to
reduce the glottal gap. Injection laryngoplasty is performed in the operating room or
as an in-office procedure. Awake procedures under local or topical anesthesia are
becoming preferable to procedures under general anesthesia. The injection materi-
als include collagen, hyaluronic acid derivatives, and hydroxylapatite. Most of the
injectables are absorbable, and thus the effects are often temporary. Medialization
thyroplasty consists in augmenting the atrophied vocal fold with some type of
implant, such as silastic, Gore-Tex, or titanium. The effects of augmentation may be
permanent, but the procedure is more invasive than injection laryngoplasty. Either
procedure is employed on a case by case basis.
Although these procedures improve glottal insufficiency, which leads to less
effort regarding phonation, the improvement of voice quality is limited because they
do not address the vibratory property of the aged vocal fold.

1.6 Rejuvenation of an Aging Voice

Some recent works have attempted to improve the tissue property of the aged vocal
fold using a regenerative approach. Growth factors are native proteins that stimu-
late the growth of cells and improve the function of the cells. Given that the aged
vocal fold fibroblasts are few in number and lose the function of the proper produc-
tion of the extracellular matrix, basic fibroblast growth factor (bFGF) or hepato-
cyte growth factor (HGF) has been proven to be potentially useful in improving the
function of the fibroblasts. The growth factors increase the number of fibroblasts,
and in the meantime stimulate the production of hyaluronic acid and modify col-
lagen turnover. Clinical trials of bFGF have shown positive regenerative effects on
aged vocal fold atrophy [8]. Further development for the rejuvenation of the aging
voice is under way.
8 S. Hirano

References

1. Williams ME. Clinical geriatrics. N Engl J Med. 2003;3249:1393–4.

2. Roy N, Stemple J, Merrill RM, Thomas L. Epidemiology of voice disorders in the elderly:
preliminary findings. Laryngoscope. 2007;117(4):628–33.
3. Costa HO, Matias C. Vocal impact on quality of life of elderly female subjects. Braz
J Otorhinolaryngol. 2005;71(2):172–8.
4. Woo P, Casper J, Colton R, Brewer D. Dysphonia in the aging: physiology versus disease.
Laryngoscope. 1992;102(2):139–44.
5. Honjo I, Isshiki N. Laryngoscopic and voice characteristics of aged persons. Arch Otolaryngol.
1980;106(3):149–50.
6. Thibeault SL, Glade RS, Li W. Comparison of telomere length of vocal folds with different
tissues: a physiological measurement of vocal senescence. J Voice. 2006;20(2):165–70.
7. Stemple J. Voice therapy: clinical case studies. Singular: San Diego; 2000.
8. Hirano S, Tateya I, Kishimoto Y, Kanemaru S, Ito J. Clinical trial of regeneration of aged vocal
folds with growth factor therapy. Laryngoscope. 2012;122:327–31.
Chapter 2
Age-Related Histological Changes of the Vocal
Folds

Masanobu Mizuta

Abstract An intricate relationship produces phonation among the vocal folds,

laryngeal muscles, cartilage, and nerves. In addition, mucous secretion from the
laryngeal glands is crucial for the pliability of the mucosal wave during phona-
tion. Age-related changes of voice are caused by the simultaneous degeneration of
these organs. To understand the mechanisms behind presbyphonia, it is most impor-
tant to elucidate the associated histological changes. Over the last few decades,
many elegant histological studies have been published. In this chapter, we describe
our current understanding of the normal histological characteristics in addition to
age-related histological changes of the organs associated with voice. This broader
understanding may lead to the development of novel treatments for presbyphonia.

2.1 Vocal Fold

The vocal fold has a distinct layered structure, comprising the epithelium, lamina
propria, and vocalis muscle. The lamina propria itself consists of three layers: the
superficial, intermediate, and deep layers. In 1974, Hirano et al. [1] proposed the
“cover-to-body theory” to explain this structure. In this model, the “cover” is made up
of the epithelium, the superficial layer, and a portion of the intermediate layer of the
lamina propria, which moves over a static “body” including the remainder of the
intermediate layer, the deep layer, and the vocalis muscle [1, 2]. The superficial layer
of the lamina propria contains loose connective tissue consisting of hyaluronic acid,
and is loosely connected to the underlying tissues. In contrast, the fibrous proteins,
including collagen and elastin fibers in the deep layer of the lamina propria, enter the
vocalis muscle and merge within the connective tissue among the muscle fibers. As a
result, the deep layer of the lamina propria is firmly connected to the vocalis muscles.
This unique relationship allows the cover, including the epithelium and superficial

M. Mizuta, MD, PhD

Department of Otolaryngology, Head & Neck Surgery,
Graduate School of Medicine, Kyoto University, Kyoto, Japan
e-mail: m_mizuta@ent.kuhp.kyoto-u.ac.jp

© Springer Nature Singapore Pte Ltd. 2017 9

K. Makiyama, S. Hirano (eds.), Aging Voice,
DOI 10.1007/978-981-10-3698-9_2
10 M. Mizuta

layer, to oscillate in a different manner from the underlying body. The intermediate
and deep layers of the lamina propria is regarded as a transitional layer. As the amount
of oscillating tissue differs by voice intensity and pitch, the cover would appear, at
times, to be thicker, as it includes more of the intermediate layer [3].

2.1.1 Epithelium

The vocal fold epithelium consists of a stratified, non-keratinized squamous epithe-

lium, whereas the ventricular folds and trachea adjacent to the vocal folds comprise
a ciliated columnar epithelium [4]. The epithelium of the vocal fold is exposed to
almost constant injury from various sources, including physical damage induced by
phonation and environmental or systemic-based irritants such as pollutants and acid
reflux [5]. The epithelium is therefore considered to play an essential role as a phys-
ical barrier protecting the underlying connective tissues from various external
threats. Recently, the relationship between the structural disruption of the epithelial
barrier and pathological conditions of the vocal fold has begun to be identified [5].
However, to date, there have been limited studies on age-related changes of the
vocal fold epithelium. One such study by Ximenes et al. [6] demonstrated a signifi-
cant reduction in epithelial cell density with increasing age. Although age-related
deterioration of the barrier function of the epithelium is possible, no evident age-­
related changes in this function have been reported.

2.1.2 Lamina Propria

The lamina propria is located immediately beneath the epithelium and superficial
to the vocalis muscle. It consists of various cells, such as fibroblasts, myofibro-
blasts, and macrophages, in addition to an abundant extracellular matrix compris-
ing fibrous proteins and interstitial proteins. The lamina propria has a trilaminar
structure, as described above. These three layers can be distinguished by their
fibrous proteins including elastin and collagen fibers. The most superficial layer is
characterized by an absence of fibrous proteins and is rich in loose connective tis-
sues. The intermediate layer has numerous elastic fibers and some collagen fibers,
whereas the deep layer is defined by an abundance of collagen fibers with fewer
elastic fibers. The border between the superficial and intermediate layers is most
evident histologically [2].

2.1.2.1 Extracellular Matrix

The extracellular matrix is composed of interstitial and fibrous proteins. The inter-
stitial proteins include proteoglycan and glycoprotein, and are located in the space
between the fibrous proteins. Both the interstitial and fibrous proteins are crucial for
2 Age-Related Histological Changes of the Vocal Folds 11

vocal fold physiology. The interstitial proteins are thought to control tissue size and
viscosity of the vocal fold, in addition to the size and density of the collagenous
fibers [3]. The fibrous proteins play an essential role in mitigating stress and helping
to maintain the shape of the vocal fold.

Hyaluronic Acid and Proteoglycans

The interstitial proteins include proteoglycans and hyaluronic acid. Proteoglycans are
made up of glycosaminoglycan chains covalently attached to a protein core, whereas
hyaluronic acid is a type of glycosaminoglycan that is not attached to proteins.
Hyaluronic acid is a biopolymer composed of repeating units of disaccharides,
which include molecules of D-glucuronic acid and N-acetylglucosamine [7].
Hyaluronic acid is distributed widely throughout the body and binds a large number
of water molecules to improve tissue hydration and cellular resistance to mechani-
cal damage. This is consistent with the abundant presence of hyaluronic acid in
regions involved in space filling and shock absorption. In the vocal folds, hyaluronic
acid has been found throughout the lamina propria. Hammond et al. [8] reported
that hyaluronic acid is especially abundant in the middle portion of the lamina pro-
pria, where it is present at significantly higher levels in males than in females.
Hyaluronic acid can strongly affect tissue viscosity in addition to shock absorption
and space filling [9, 10]. Through ex vivo experiments, Gray et al. [10] showed that
hyaluronic acid is an essential molecule affecting the viscosity of the vocal folds.
In 2014, Branco et al. [11] compared the levels of hyaluronic acid among male
larynges from three different age groups (30–50 years, 60–75 years, and over
76 years of age). The results showed that the level of hyaluronic acid in the lamina
propria in both of the geriatric groups was lower than in the adult group (30–
50 years). These results are supported by a recent study in skin, in which Oh et al.
[12] demonstrated a significant decrease in epidermal hyaluronic acid in the but-
tocks of aged subjects (70–80 years) compared with young subjects (20–33 years).
Among the proteoglycans, both decorin and fibromodulin have been identified in
the lamina propria, where their expression is predominantly layer-specific [13].
Decorin localizes to the superficial layer of the lamina propria, whereas fibromodu-
lin is found in the intermediate and deep layers. Both decorin and fibromodulin have
a leucine-rich protein core and a small, compact molecular size. They bind to col-
lagen type I and reportedly regulate the form of the collagen fibers. Decorin has also
been shown to play a key role in the extracellular matrix, where it regulates various
growth factors [14–17]. Furthermore, experimental studies have demonstrated that
decorin decreases pulmonary fibrosis [18] and reduces collagen gel contraction by
hypertrophic scar fibroblasts [19]. These studies suggested the effects of decorin on
the maintenance of the tissue pliability. In addition to decorin, fibromodulin has also
been associated with wound healing [19].
Age-related changes in decorin have been investigated in the skin. Carrino et al.
[20] reported that the major difference in decorin between young and older sub-
jects was a reduction in GAG length in the older group. Similarly, Li et al. [21]
demonstrated that the molecular size of decorin in aged skin is significantly