The structural composition of the human vocal fold changes with age (see e.g.
HIRANO et al. 1983; HAMMOND et al. 1998, 2000; ISHII et al. 2000). Medical interest in these processes is focused on their negative functional effects, as e.g. the
‘ageing of the voice’ (BIEVER and BLESS 1989; HIRANO et al. 1989). As already mentioned in the previous chapter 2.3 (The stratigraphical organisation of the lamina propria), the phoniatrical interest in animals mostly focuses on their use as models for humans (see e.g. GARRETT et al. 2000; JIANG et al. 2001; HAHN et al. 2005). In this context, a lack of knowledge on age-related changes in the vocal folds of pigs (KOCH et al. 2010) may limit the potential benefit from their use as an animal model.
Several studies on the human vocal fold deal with maturation (see e.g. HIRANO et al.
1983; HAMMOND et al. 1998, 2000; ISHII et al. 2000; SATO et al. 2001 a). The findings of these studies are rather inconsistent, which is probably due to the heterogeneity of specimens: Most examinations were either limited to very young (foetal to infantile) specimens (see e.g. SATO et al. 2001 a; NITA et al. 2009), or compared specimens of newborns or infants with those of adult or old humans (see e.g. HAMMOND et al. 1998, 2000; HIRANO et al. 1999; FAYOUX et al. 2004); other studies lacked specimens of a broad age span (e.g. no samples of 6-11 year-old children were examined by ISHII et al. [2000]). Nevertheless, all of these data taken together served well to describe the basic features of maturation as follows:
In newborn children, the entire lamina propria is made up of abundant Ground Substance and only sparse homogeneously distributed fibres (HIRANO et al. 1983;
ISHII et al. 2000; SATO et al. 2001 a). In this regard, the entire lamina propria resembles the SLLP of the adult vocal fold (HIRANO et al. 1983). Accordingly, the vocal fold of newborns does not contain a structure which can be designated as a vocal ligament (HIRANO et al. 1983; ISHII et al. 2000; SATO et al. 2001 a).
Between infancy and adulthood, the amounts of collagen and elastic fibres increase significantly (HAMMOND et al. 1998, 2000). These fibres are mainly produced by Vocal Fold Stellate Cells (SATO et al. 2001 b). This special type of fibroblast is accumulated in the maculae flavae, which are located in the anterior and posterior ends of the membranous part of the vocal fold (HIRANO et al. 1983; SATO et al.
2001 b). The fibres produced in the maculae flavae extend towards the middle of the vocal fold (HIRANO et al. 1983; SATO et al. 2001 a). According to SATO et al.
(2001 a), collagen and reticular fibres are produced early in infancy (age not further specified), and serve as stabilising scaffolds for the extension of elastic fibres. They thus appear in the midportion of the vocal fold prior to the elastic fibres (SATO et al.
2001 a).
The stages of development of the adult fibre stratigraphy were examined in detail by HIRANO et al. (1983) and ISHII et al. (2000). An immature ligamentous structure – characterised by a homogeneous distribution of collagen and elastic fibres (rather than an arrangement in clearly differentiated layers) – was occasionally found in children of 1-4 years of age, and was always present in children older than 4 years (HIRANO et al. 1983). According to ISHII et al. (2000), the development of the distinct adult stratigraphical organisation begins later in life: In specimens of 5-year-old children, longitudinally arranged collagen and elastic fibres were still evenly distributed throughout all layers of the lamina propria (ISHII et al. 2000). Later on, first signs of a differentiation of layers were found in individuals aged 12 years (ISHII et al. 2000). However, no samples were examined of children aged 6-11. The completion of the mature vocal fold structure was fairly consistently described as occurring at 16 years (HIRANO et al. 1983), or 17 years (ISHII et al. 2000), respectively.*
* These data refer to male specimens in both studies (HIRANO et al. 1983; ISHII et al. 2000). No reference was made to female individuals.
The process of ageing of the vocal fold appears difficult to assess, as there is no unanimous agreement on the age at which ’ageing’ of the vocal fold actually begins (see e.g. HIRANO et al. 1983, 1989; KAHANE 1983; ISHII et al. 1996; HAMMOND et al. 1998, 2000; BUTLER et al. 2001; SATO et al. 2002; ROBERTS et al. 2011):
Some authors attribute structural changes encountered at the age of 40 years to processes of ageing (HIRANO et al. 1983), while others have classified the status of 63-year-old specimens as ‘adult’ instead of ‘old’ (ISHII et al. 1996).
The main feature of ageing is a decrease in number and activity of the Vocal Fold Stellate Cells in the maculae flavae (HIRANO et al. 2000; SATO et al. 2010). This decrease causes a decrease of the turnover rate of the fibrous components in the lamina propria: Production of fibres is slowed down, as is their breakdown (SATO and HIRANO 1995; GRAY, 2000). In the aged vocal fold, fibres thus become older before being degraded and replaced by new fibres (GRAY, 2000). As a consequence, ageing is characterised by changes in the structure and in the amounts of fibres (KAHANE 1983; HIRANO et al. 1983, 1989; SATO et al. 2002;
SATO and HIRANO 1995, 1997; HAMMOND et al. 1998, 2000; ROBERTS et al.
2011).
Structural alterations in collagen and elastic fibres result in an increase in fibre diameter (SATO et al. 2002; HAMMOND et al. 1998), and also in a greater variation of fibre diameters (SATO and HIRANO 1997; SATO et al. 2002). With age, the arrangement of fibres becomes less orderly (HIRANO et al. 1983; ISHII et al. 1996;
SATO and HIRANO 1997); an increased number of cross links develops between fibres (SATO and HIRANO 1997; BAILEY 2001), and collagen fibres display irregular outlines (SATO et al. 2002).
An increase in the amounts of collagen fibres in the aged vocal fold of humans is most pronounced in the DLLP (HIRANO et al. 1983, 1989; HAMMOND et al. 2000;
SATO et al. 2002; ROBERTS et al. 2011). Yet in some individuals, collagen fibre amounts have been reported to increase evenly throughout the entire lamina propria.
In these cases, a layered organisation was no longer visible in the aged vocal fold (SATO et al. 2002).
The effect of ageing on the amounts of elastic fibres is described inconsistently (see HIRANO et al. 1983; KAHANE, 1983; HAMMOND et al. 1998; ROBERTS et al.
2011), even though all of the reviewed studies applied similar methods: Selectively stained elastic fibres in paraffin sections were examined by light microscopy.
However, HIRANO et al. (1983) and KAHANE (1983) performed a descriptive analysis, while HAMMOND et al. (1998) and ROBERTS et al. (2011) chose a histomorphometrical procedure. The studies by HIRANO et al. (1983) and KAHANE (1983) revealed a decrease in elastic fibre amounts throughout the entire lamina propria due to a degradation of fibres with age. In contrast, HAMMOND et al. (1998) described a significant age-dependent increase in elastic fibre amounts throughout the lamina propria, but predominantly in the ILLP. Finally, an almost complete absence of elastic fibres in the SLLP combined with high amounts of elastic fibres in the DLLP was reported by ROBERTS et al. (2011).
The human vocal folds are subject to extensive structural stages during maturation and ageing. Considering this, similar extents of age-related changes can be suspected in the porcine vocal folds. (An investigation of different stages of structural development of the porcine vocal folds may thus enable the determination of the adequate age of the pig to be used as a model.)
3 Materials and Methods