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 phonation. Age-related changes of voice are caused by the simultaneous degeneration of these organs. To understand the mechanisms behind presbyphonia, it is most important 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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Hirano M. Morphological structure of the vocal cord as a vibrator and its variations. Folia Phoniatr (Basel). 1974;26(2):89–94.
Hammond TH, Gray SD, Butler JE. Age- and gender-related collagen distribution in human vocal folds. Ann Otol Rhinol Laryngol. 2000;109(10 Pt 1):913–20.
Gray SD, Titze IR, Alipour F, et al. Biomechanical and histologic observations of vocal fold fibrous proteins. Ann Otol Rhinol Laryngol. 2000;109(1):77–85.
Stiblar-Martincic D. Histology of laryngeal mucosa. Acta Otolaryngol Suppl. 1997;527:138–41.
Levendoski EE, Leydon C, Thibeault SL. Vocal fold epithelial barrier in health and injury: a research review. J Speech Lang Hear Res. 2014;57(5):1679–91. doi:10.1044/2014_JSLHR-S-13-0283.
Ximenes Filho JA, Tsuji DH, do Nascimento PH, et al. Histologic changes in human vocal folds correlated with aging: a histomorphometric study. Ann Otol Rhinol Laryngol. 2003;112(10):894–8.
Salwowska NM, Bebenek KA, Zadlo DA et al. Physiochemical properties and application of hyaluronic acid: a systematic review. J Cosmet Dermatol. 2016; doi: 10.1111/jocd.12237.
Hammond TH, Zhou R, Hammond EH, et al. The intermediate layer: a morphologic study of the elastin and hyaluronic acid constituents of normal human vocal folds. J Voice. 1997;11(1):59–66. S0892-1997(97)80024-0 [pii].
Laurent TC, Laurent UB, Fraser JR. Functions of hyaluronan. Ann Rheum Dis. 1995;54(5):429–32.
Gray SD, Titze IR, Chan R, et al. Vocal fold proteoglycans and their influence on biomechanics. Laryngoscope. 1999;109(6):845–54.
Branco A, Rodrigues SA, Fabro AT, et al. Hyaluronic acid behavior in the lamina propria of the larynx with advancing age. Otolaryngol Head Neck Surg. 2014;151(4):652–6. doi:10.1177/0194599814544673.
Oh JH, Kim YK, Jung JY, et al. Intrinsic aging- and photoaging-dependent level changes of glycosaminoglycans and their correlation with water content in human skin. J Dermatol Sci. 2011;62(3):192–201. doi:10.1016/j.jdermsci.2011.02.007.
Pawlak AS, Hammond T, Hammond E, et al. Immunocytochemical study of proteoglycans in vocal folds. Ann Otol Rhinol Laryngol. 1996;105(1):6–11.
Moscatello DK, Santra M, Mann DM, et al. Decorin suppresses tumor cell growth by activating the epidermal growth factor receptor. J Clin Invest. 1998;101(2):406–12. doi:10.1172/JCI846.
Vial C, Gutierrez J, Santander C, et al. Decorin interacts with connective tissue growth factor (CTGF)/CCN2 by LRR12 inhibiting its biological activity. J Biol Chem. 2011;286(27):24242–52. doi:10.1074/jbc.M110.189365.
Yamaguchi Y, Mann DM, Ruoslahti E. Negative regulation of transforming growth factor-beta by the proteoglycan decorin. Nature. 1990;346(6281):281–4. doi:10.1038/346281a0.
Kwan P, Ding J, Tredget EE. MicroRNA 181b regulates decorin production by dermal fibroblasts and may be a potential therapy for hypertrophic scar. PLoS One. 2015;10(4):e0123054. doi:10.1371/journal.pone.0123054.
Kolb M, Margetts PJ, Galt T, et al. Transient transgene expression of decorin in the lung reduces the fibrotic response to bleomycin. Am J Respir Crit Care Med. 2001;163(3 Pt 1):770–7. doi:10.1164/ajrccm.163.3.2006084.
Zheng Z, Jian J, Velasco O, et al. Fibromodulin enhances angiogenesis during cutaneous wound healing. Plast Reconstr Surg Glob Open. 2015;2(12):e275. doi:10.1097/GOX.0000000000000243.
Carrino DA, Calabro A, Darr AB, et al. Age-related differences in human skin proteoglycans. Glycobiology. 2011;21(2):257–68. doi:10.1093/glycob/cwq162.
Li Y, Liu Y, Xia W, et al. Age-dependent alterations of decorin glycosaminoglycans in human skin. Sci Rep. 2013;3:2422. doi:10.1038/srep02422.
Dion GR, Jeswani S, Roof S, et al. Functional assessment of the ex vivo vocal folds through biomechanical testing: a review. Mater Sci Eng C Mater Biol Appl. 2016;64:444–53. doi:10.1016/j.msec.2016.04.018.
Chan RW, Fu M, Young L, et al. Relative contributions of collagen and elastin to elasticity of the vocal fold under tension. Ann Biomed Eng. 2007;35(8):1471–83. doi:10.1007/s10439-007-9314-x.
Hammond TH, Gray SD, Butler J, et al. Age- and gender-related elastin distribution changes in human vocal folds. Otolaryngol Head Neck Surg. 1998;119(4):314–22.. S0194599898003234 [pii].
Schwartz E, Fleischmajer R. Association of elastin with oxytalan fibers of the dermis and with extracellular microfibrils of cultured skin fibroblasts. J Histochem Cytochem. 1986;34(8):1063–8.
Kahane JC. Connective tissue changes in the larynx and their effects on voice. J Voice. 1987;1(1):27–30.
Hirano M, Kurita S, Nakashima T. Growth, development, and aging of human voice folds. In: Bless D, Abbs J, editors. Vocal physiology. San Diego: College Hill Press; 1983. p. 22–43.
Sato K, Hirano M. Age-related changes of elastic fibers in the superficial layer of the lamina propria of vocal folds. Ann Otol Rhinol Laryngol. 1997;106(1):44–8.
Myllyharju J, Kivirikko KI. Collagens, modifying enzymes and their mutations in humans, flies and worms. Trends Genet. 2004;20(1):33–43.. S0168-9525(03)00319-6 [pii].
Hahn MS, Kobler JB, Zeitels SM, et al. Quantitative and comparative studies of the vocal fold extracellular matrix II: collagen. Ann Otol Rhinol Laryngol. 2006;115(3):225–32.
Sato K, Hirano M, Nakashima T. Age-related changes of collagenous fibers in the human vocal fold mucosa. Ann Otol Rhinol Laryngol. 2002;111(1):15–20.
Catten M, Gray SD, Hammond TH, et al. Analysis of cellular location and concentration in vocal fold lamina propria. Otolaryngol Head Neck Surg. 1998;118(5):663–7.. S0194599898001478 [pii].
Hirano M, Sato K, Nakashima T. Fibroblasts in geriatric vocal fold mucosa. Acta Otolaryngol. 2000;120(2):336–40.
Sato K, Hirano M. Age-related changes of the macula flava of the human vocal fold. Ann Otol Rhinol Laryngol. 1995;104(11):839–44.
Chen X, Thibeault SL. Characteristics of age-related changes in cultured human vocal fold fibroblasts. Laryngoscope. 2008;118(9):1700–4. doi:10.1097/MLG.0b013e31817aec6c.
Faryniarz DA, Chaponnier C, Gabbiani G, et al. Myofibroblasts in the healing lapine medial collateral ligament: possible mechanisms of contraction. J Orthop Res. 1996;14(2):228–37. doi:10.1002/jor.1100140210.
Shi Y, Pieniek M, Fard A, et al. Adventitial remodeling after coronary arterial injury. Circulation. 1996;93(2):340–8.
Branco A, Bartley SM, King SN, et al. Vocal fold myofibroblast profile of scarring. Laryngoscope. 2016;126(3):E110–7. doi:10.1002/lary.25581.
Boseley ME, Hartnick CJ. Development of the human true vocal fold: depth of cell layers and quantifying cell types within the lamina propria. Ann Otol Rhinol Laryngol. 2006;115(10):784–8.
Subotic R, Vecerina S, Krajina Z, et al. Histological structure of vocal fold lamina propria in foetal larynx. Acta Otolaryngol. 1984;97(5–6):403–6.
Sato K, Hirano M, Nakashima T. Fine structure of the human newborn and infant vocal fold mucosae. Ann Otol Rhinol Laryngol. 2001;110(5 Pt 1):417–24.
Ishii K, Yamashita K, Akita M, et al. Age-related development of the arrangement of connective tissue fibers in the lamina propria of the human vocal fold. Ann Otol Rhinol Laryngol. 2000;109(11):1055–64.
Hartnick CJ, Rehbar R, Prasad V. Development and maturation of the pediatric human vocal fold lamina propria. Laryngoscope. 2005;115(1):4–15.. 00005537-200501000-00003 [pii].
De Campos D, Ellwanger JH, da Costa Rosa JP, et al. Morphology of fetal vocal fold and associated structures. J Voice. 2013;27(1):5–10. doi:10.1016/j.jvoice.2012.09.002.
Nita LM, Battlehner CN, Ferreira MA, et al. The presence of a vocal ligament in fetuses: a histochemical and ultrastructural study. J Anat. 2009;215(6):692–7. doi:10.1111/j.1469-7580.2009.01146.x.
Nishida N, Taguchi A, Motoyoshi K, et al. Age-related changes in rat intrinsic laryngeal muscles: analysis of muscle fibers, muscle fiber proteins, and subneural apparatuses. Eur Arch Otorhinolaryngol. 2013;270(3):975–84. doi:10.1007/s00405-012-2231-0.
Wells L, Edwards KA, Bernstein SI. Myosin heavy chain isoforms regulate muscle function but not myofibril assembly. EMBO J. 1996;15(17):4454–9.
Rodeno MT, Sanchez-Fernandez JM, Rivera-Pomar JM. Histochemical and morphometrical ageing changes in human vocal cord muscles. Acta Otolaryngol. 1993;113(3):445–9.
Narici MV, Maffulli N. Sarcopenia: characteristics, mechanisms and functional significance. Br Med Bull. 2010;95:139–59. doi:10.1093/bmb/ldq008.
Jang YC, Van Remmen H. Age-associated alterations of the neuromuscular junction. Exp Gerontol. 2011;46(2–3):193–8. doi:10.1016/j.exger.2010.08.029.
Kersing W, Jennekens FG. Age-related changes in human thyroarytenoid muscles: a histological and histochemical study. Eur Arch Otorhinolaryngol. 2004;261(7):386–92. doi:10.1007/s00405-003-0702-z.
Malmgren LT, Fisher PJ, Bookman LM, et al. Age-related changes in muscle fiber types in the human thyroarytenoid muscle: an immunohistochemical and stereological study using confocal laser scanning microscopy. Otolaryngol Head Neck Surg. 1999;121(4):441–51. S0194599899004295 [pii].
Grimby G. Muscle performance and structure in the elderly as studied cross-sectionally and longitudinally. J Gerontol A Biol Sci Med Sci. 1995;50 Spec No:17–22.
Sato T, Tauchi H. Age changes in human vocal muscle. Mech Ageing Dev. 1982;18(1):67–74. 0047-6374(82)90031-8 [pii].
Martins RH, Benito Pessin AB, Nassib DJ, et al. Aging voice and the laryngeal muscle atrophy. Laryngoscope. 2015;125(11):2518–21. doi:10.1002/lary.25398.
Malmgren LT, Jones CE, Bookman LM. Muscle fiber and satellite cell apoptosis in the aging human thyroarytenoid muscle: a stereological study with confocal laser scanning microscopy. Otolaryngol Head Neck Surg. 2001;125(1):34–9. S0194-5998(01)18123-4 [pii].
Mortelliti AJ, Malmgren LT, Gacek RR. Ultrastructural changes with age in the human superior laryngeal nerve. Arch Otolaryngol Head Neck Surg. 1990;116(9):1062–9.
Nakai T, Goto N, Moriyama H, et al. The human recurrent laryngeal nerve during the aging process. Okajimas Folia Anat Jpn. 2000;76(6):363–7.
Tiago R, Pontes P, do Brasil OC. Age-related changes in human laryngeal nerves. Otolaryngol Head Neck Surg. 2007;136(5):747–51.. S0194-5998(06)03584-4 [pii].
Perie S, St Guily JL, Callard P, et al. Innervation of adult human laryngeal muscle fibers. J Neurol Sci. 1997;149(1):81–6. S0022510X97053951 [pii].
Gambino DR, Malmgren LT, Gacek RR. Age-related changes in the neuromuscular junctions in the human posterior cricoarytenoid muscles: a quantitative study. Laryngoscope. 1990;100(3):262–8. doi:10.1288/00005537-199003000-00010.
Takeda N, Thomas GR, Ludlow CL. Aging effects on motor units in the human thyroarytenoid muscle. Laryngoscope. 2000;110(6):1018–25.. 00005537-200006000-00025 [pii].
Turk ML, Hogg DA. Age changes in the human laryngeal cartilages. Clin Anat. 1993;6(3):154–62.
Roncallo P. Researches about ossification and conformation of the thyroid cartilage in men. Acta Otolaryngol. 1948;36(2):110–34.
Harrison DF, Denny S. Ossification within the primate larynx. Acta Otolaryngol. 1983;95(5–6):440–6.
De la Grandmaison GL, Banasr A, Durigon M. Age estimation using radiographic analysis of laryngeal cartilage. Am J Forensic Med Pathol. 2003;24(1):96–9. doi:10.1097/01.PAF.0000052756.47528.6D.
Bak-Pedersen K, Nielsen KO. Subepithelial mucous glands in the adult human larynx. Studies on number, distribution and density. Acta Otolaryngol. 1986;102(3–4):341–52.
Gracco C, Kahane JC. Age-related changes in the vestibular folds of the human larynx: a histomorphometric study. J Voice. 1989;3(3):204–12.
Hirano M. Phonosurgery: basic and clinical investigations. Otologia Fukuoka. 1975;21:239–442.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Mizuta, M. (2017). Age-Related Histological Changes of the Vocal Folds. In: Makiyama, K., Hirano, S. (eds) Aging Voice. Springer, Singapore. https://doi.org/10.1007/978-981-10-3698-9_2
Download citation
DOI: https://doi.org/10.1007/978-981-10-3698-9_2
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-10-3697-2
Online ISBN: 978-981-10-3698-9
eBook Packages: MedicineMedicine (R0)