The nail is composed of a “dead” corneum product, nail plate, and four specialized epithelia: proximal nail fold, matrix, nail bed, and hyponychium.

Nail system is affected during aging: The size of keratinocytes in the nail plate increases, the skin in the nail bed thickens, and elasticity and the number of blood vessels decrease. There are also changes in the chemical composition (Ca and Fe) [14]. Senile nails may appear pale, matte, and opaque, varying in color from white, yellow, black, or gray. Therefore, nail growth decreases by 0.5 % per year from age 25 to 100 years (average growth is 0.1 mm per day in hands and 0.03 mm per day in feet) [15]. One study found that blood flow was reduced up to 30 % in the nail bed in postmenopausal women compared with those who were premenopausal or HRT users [16]. Another study reports that with aging there is a decrease of calcium content in the nails, while magnesium increases [17]. On the other hand, during pregnancy, the nails become brittle and fragile, with cases of onycholysis and leukonychia due to the influence of the hormonal and immune burden [18].

Pilosebaceous follicles are formed by the association of sebaceous glands and hair follicles. Isolated sebaceous glands are rare, being located in the oral mucosa, eyelids, nipples, and the female labia. Hair follicles have an intrinsic rhythm alternating regeneration cycles with hair fall cycles. These cycles are called “anagen” (growth), “telogen” (idle), and “catagen” (involution), and its rate can be influenced by hormonal or nutritional factors.

During pregnancy, the proportion of follicles in anagen increase significantly by the effect of higher estrogen concentrations, where as in the postpartum, with the drop in estrogen and changes in growth factors, greater follicle synchronization in fall cycle is observed, being the hair loss clinically detectable. A possible protective effect of estrogen is also indirectly suggested by studies that reported thinner hair and a further decline by the use of tamoxifen [19] and more recently with the use of aromatase inhibitors.

Typically, the secretion of sebaceous glands increases in pregnant women by the action of estrogen and growth factors [18]. Besides, in hyperandrogenic states, hormones have also significant impact on these glands, especially related to the amount and composition of phospholipids. Estrogens increase production of the sebaceous glands, and androgens increase this production in excess causing undesirable states (acne, hirsutism, etc.).

The eccrine sweat is a physiological mechanism for regulating body temperature. Eccrine secretion contains water, electrolytes, metals, organic compounds, and macromolecules. Without sweating hyperthermia, exhaustion, heat stroke, and death might occur.

These glands are numerous in soles of the feet, hands, armpits, and forehead and less on the back. It is known that the control and regulation of these glands are by the sympathetic nervous system, which releases acetylcholine. However, there are data showing a modulating effect by sex hormones. Estrogens have the ability to increase potassium conductance in eccrine sweat gland cells by opening K/Ca channels [20]. In addition, estradiol 17-beta may control the intracellular calcium concentration [21], controlling the release of intracellular calcium stores. Several studies have found that during pregnancy there is an overactivity of the eccrine glands in different locations of the body except the hands [18].

The apocrine glands are located mainly in the armpits and perineum. Its activity begins shortly before puberty, and thus its development is believed to be associated with hormonal changes that occur during this period. There is controversy over whether or not the activity in these glands decreases during pregnancy.

The changes that occur in the skin as a consequence of time define aging skin (Table 25.2).

The biological clock affects both the skin and internal organs in an identical way. However, there are numerous cosmetic techniques to improve the aging aspect, even only in the external component [22].

There are several theories to explain aging; some of them are based on genetic factors limiting the ability of cell proliferation. Other theories are based on the influence of external environmental agents such as exposure to wind, ultraviolet radiation, sun, heat or pollution, toxic habits (smoking or drinking), sleep disorders, deficient nutrition, and muscle movements [23].

The programmatic theory is based on telomere shortening [24]. Telomeres are the terminal portions of the chromosomes that protect the genic data. During cell mitosis, DNA polymerase is unable to replicate all the terminal base pairs of each chromosome, which defines a progressive shortening with each cell division cycle. Telomerase reverse transcriptase has the ability to replicate these chromosomal ends. The number of telomerases shortens up to 30 % when a person ages, and this leads to DNA instability and interruption of cell cycle or apoptosis.

The reduced ability of cell division is called cell senescence; some authors believe that during the evolution of multicellular organisms, this phenomenon acts as a cancer-preventive mechanism. The aged cells present very short telomeres with irreversible disruption of growth, resistance to apoptosis, and altered cell differentiation. Genes in senescence, involved in the G1 phase and aging cells, lose the ability to induce the genes necessary for advancing the G1 phase of the cell cycle, including c-Fos and certain transcription factors [25]. Other senescence-associated genes that are overexpressed encode various protein products, such as fibronectin and proteases (collagenase and stromelysin) that are involved in the regulation of matrix in the skin structure. This fact and the decreased level of tissue inhibitors of metalloproteinase induce the weakness of skin matrix [26].

During aging, there are decreased secretion and production of several hormones. The best known are estrogen, testosterone, dehydroepiandrosterone (DHEA), and its sulfate (DHEAS) [27, 28]. Other hormones like melatonin, insulin, cortisol, thyroxin, and growth hormone production also decrease with age [29]. Additionally, many cytokines alter its functionality with the decrease of receptor number and increasing senescence of different cells such as fibroblasts. All these changes induce gradually aberrant cellular response to environmental factors that ends in cell death [30].

On the other hand, the stochastic theory is based on the assumption that oxygen consumption is related to aging [31]. Oxygen, although necessary for life, may cause harmful effects such as peroxidation of fatty acid in cell membranes, changes in bases of single-stranded DNA, chromatin change, breaks of DNA, cross-links between DNA proteins, modifications of the carboxyl, and loss of sulfhydryl groups leading to enzyme inactivation and increased proteolysis. Since the efficiency of the antioxidant defense systems is not absolute, in the course of life, cells accumulate molecular oxidative injury that sometimes leads to apoptotic cell death. The immune system plays two special functions: defense against external aggression and internal immune surveillance. With aging, functional B and T lymphocytes alter their activity, and Langerhans cells decrease in number and with associate impaired immune response. These changes contribute to the increased incidence of infections and malignancies in the elderly [32].

The skin aging process involves two pathophysiologic routes: intrinsic aging caused by the decrease in the metabolic functions of the cells due to the time elapsed since birth and the extrinsic aging that is caused by factors out of the subject, i.e., chronic exposure to ultraviolet radiation and pollution (Table 25.3). The most widely accepted theory is that aging is a combination of both during the course of a lifetime.

Intrinsic aging affects all skin layers and all structures included in the skin as glands, vessels, nerves, and its different cells. To these changes, alterations caused by hormonal decline are summed. The sum of both will trigger not only aging but also precancerous and tumor cells. In Table 25.4 are summarized the different changes observed with aging in the skin structure.