The external phenotype of aging

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Abstract

Aging is widely studied as a physiological process. Segmental aging can also occur prematurely in Mendelian disorders, and these can act this way as excellent sources of information, specifically for the underlying mechanisms. Adequate recognition of such aging characteristics in Mendelian disorders needs a well-defined phenotype of aging. Here the external phenotype of aging is described that can be recognized in the consulting room without major additional studies. Existing definitions of the signs and symptoms in Elements of Morphology or Human Phenotype Ontology are added or a new definition is suggested if none is available.

Introduction

Almost invariably we realize someone is of advanced age already when he or she is entering a room, because we recognize the phenotype, the body posture and movements, and possibly visual and auditory abilities of the aged person. Even just evaluating someone's face or hands is often sufficient to come to this conclusion (Rhodes, 2009; Yadav et al., 2014; Bains et al., 2006), as for instance many paintings tell us as well (Fig. 1). This is irrespective of gender and ethnicity (Yadav et al., 2014). Evaluating only someone's hands allow people already to roughly estimate the age of that person (Bains et al., 2006).

Remarkably, despite a continuously enormous number of publications on aging the full series of characteristics of the external phenotype of (physiological) aging seems not to have been defined. Only some signs were defined as part of the series of publications “Elements of Morphology” which aim at defining the human external phenotype (Allanson et al., 2009a, Allanson et al., 2009b) and the “Human Phenotype Ontology” which adopted the definitions of the Elements series for corresponding terms (Kohler et al., 2017). Defining all characteristics of physiological aging is of importance however, as it will also allow us to recognize the individual characteristics and combinations of characteristics of aging in Mendelian disorders.

Here I suggest which characteristics define physiological aging, and their definitions. I limit myself to those characteristics that can be recognized by physical exam or simple additional studies in the consulting room.

The main characteristics of aging can be considered common knowledge, but are subjective and not well defined. For the face aging can be subdivided into changes in the various structural layers of the face, so skeleton, muscle, fat and skin (Fitzgerald et al., 2010; Cotafana et al., 2016). There is a limited number of studies available using 3D scanning that allows a more objective evaluation of the complete face (Chen et al., 2015; Farazdaghi, 2018; Garson et al., 2017; Modabber et al., 2020) or of a specific part of the face, such as the forehead (Yi, 2015), orbits (Kahn and Shaw, 2008), eyebrows (Papageorgiou et al., 2012), cheeks (Saito et al., 2008), and lips (De Menezes et al., 2011). Some studies also mentioned (limited) racial differences in aging (Imaizumi et al., 2015; Yi, 2015; Kim et al., 2015) and between sexes (Modabber et al., 2020; Farazdaghi, 2018), but irrespective of ethnicity and gender, the studies allow classification of a number of facial characteristics as becoming more clear during aging: more upright course of the lower part of the forehead, deeply set eyes, flat malae, depressed nasal tip by decrease of support of the nose and collapse of the nasal alae, sagging cheeks, prominent nasolabial folds, downturned corners of the mouth, decrease of mandibular body height and length causing a small, receding chin, increased skin wrinkling, and a pale skin with localized hyperpigmentations. Often a sign is not caused by aging of a single structural layer of the face, but by several layers simultaneously, and the various signs influence one another as well (see below).

The aging face has also been studied by anthropometric measurements (Farkas et al., 2004, 2005) but these 2D data do not add further characteristics to the available 3D data as the 2D data can be derived from the 3D data. Otherwise there is no other objective means to determine external facial phenotype of aging.

For the hands and feet, a single, preliminary 3D study is available (Hoevenaren et al., 2017) but otherwise no objective studies of the phenotype in aging that do not rely on expensive equipment have been published (Moon and Lee, 2018). The aging characteristics of the distal limbs cannot be determined by simply anthropometrics. There is a large number of manuscripts that describe the aging manifestations which are based on common knowledge, and which mention lack of fat tissue, well visible veins (mainly caused by the lack of fat tissue), decrease of muscle bulk, thin and fragile skin with localized hyperpigmentations, and decreased grip strength (Carmelli et al., 2003; Bohannon, 2019).

I have based the characteristics of the external phenotype of aging on the above mentioned signs, to which I added other signs of which the occurrence in aging is part of common knowledge: greying of hair; loss of hair; fine hair; hearing loss; cataract; loss of permanent teeth; sarcopenia; decreased joint mobility; loss of skin elasticity; skin fragility; loss of body height; loss of fertility/hypogonadism; menopause; tremor; and loss of cognitive abilities. The characteristics are summarized in Table 1, indicating their definitions. The definitions are those of the Elements of Morphology (EoM) series of papers and Human Phenotype Ontology (HPO) if available. Existing HPO identification numbers are added. A cartoon showing the characteristics is available in the Suppl materials (Fig. S1). The characteristics are described below. If reliable prevalence data or data at which the signs or symptom arises are available, these are added, as especially the age of onset may be needed to determine whether a sign or symptom is occurring prematurely. The interested reader is referred to the references for more details.

Section snippets

Greying of hair

Greying of hair (also called achromotrichia or canities) is common. The ‘50 rule’ indicated that at age 50 years 50% of the population has at least 50% grey hair, but a large population study has indicated that at 50 years 6–23% of the population has 50% grey hair, and that this percentage is variable depending on ethnicity and natural hair colour (Panhard et al., 2012). Average age of onset in Caucasians is 34 years ± 9.6 years and in Blacks 43.9 years ± 10.3 years (Kumar et al., 2018). The

Discussion

The characteristics and their definitions described here can be useful when studying (physiological) aging characteristics in humans in general, but also in studying those in Mendelian disorders. Mendelian disorders can be excellent resources of common processes in human, and can indicate pathogenetic pathways involved in these common processes (Boycott et al., 2017; Hebbring, 2019). This may include aging as well. Mendelian disorders that demonstrate signs or symptoms that occur in aging are

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