Aging Skin: Histology, Physiology, and Pathology Jeannie Khavkin, MDa,*, David A.F. Ellis, MD, FRCSCa,b KEYWORDS Skin histology Skin physiology Skin aging Skin architecture Photoaging Skin is a complex organ covering the entire the dermis and hypodermis arise from mesoderm. surface of the body. It provides a protective During the fourth week of embryonic development, physical barrier between the body and the environ- a single layer of ectoderm surrounds the embryo. ment, preventing losses of water and electrolytes, This simple epithelium overlies a loosely organized reducing penetration by chemicals, and protecting layer of undifferentiated mesoderm known as against pathogenic microorganisms. The skin is mesenchyme. At about 6 weeks, the ectoderm important in regulation of body temperature and and the underlying mesoderm begin to proliferate provides immunologic surveillance. It contains and differentiate. Hair follicles, nails, and glands sensory and autonomic nerves and sensory recep- begin to develop in the third month. By the end tors, which detect incoming stimuli of touch, vibra- of the third month, regular bundles of collagen tion, pressure, temperature, pain, and itching. appear in the dermis. The embryonic connective Skin is an important component of outward tissue below the dermis develops into the subcu- beauty and is the focus of various cutaneous taneous layer of loose connective tissue charac- surgical and nonsurgical procedures. Skin changes terized by fat islands.1 associated with chronologic aging or photoaging, such as wrinkling, laxity, and changes in pigmenta- The Epidermis tion, prompt patients to seek cosmetic procedures to improve the appearance of their skin. This article The normal epidermis is a stratified squamous reviews skin histology and physiology as well as epithelium undergoing continuous renewal. The changes associated with cutaneous aging. major cell in the epidermis is the ectodermally derived keratinocyte, making up approximately NORMAL SKIN ARCHITECTURE 95% of the epidermal cells. As the keratinocyte progressively moves from its attachment to the Skin is organized into 3 layers: the epidermis, the basement membrane to the skin surface, it forms dermis, and the hypodermis (Fig. 1). The fine several morphologically distinct epidermal layers: structure of the skin shows considerable regional stratum basale or stratum germinativum, stratum variations in epidermal and dermal thickness, spinosum, stratum granulosum, and stratum cor- distribution of epidermal appendages, and mela- neum (Fig. 2). On the palms and soles, an addi- nocyte content. Skin is glabrous or non–hair- tional layer, stratum lucidum, can be identified bearing on the palms and soles, whereas between the stratum corneum and stratum granu- hair-bearing skin covers the rest of the body. losum. Other cell types found in the epidermis Embryologically, the epidermis and its append- include melanocytes, Langerhans cells, and ages develop from the surface ectoderm, and Merkel cells. The authors have nothing to disclose. a Division of Facial Plastic Surgery, Department of Otolaryngology-Head and Neck Surgery, University of Toronto, R. Fraser Elliott Building, 190 Elizabeth Street, Room 3S-438, Toronto, ON M5G 2N2, Canada b Art of Facial Surgery, 167 Sheppard Avenue West, Toronto, ON M2N 1M9, Canada * Corresponding author. 653 North Town Center Drive, Suite 308, Las Vegas, NV 89144. E-mail address: [email protected] Facial Plast Surg Clin N Am 19 (2011) 229–234 doi:10.1016/j.fsc.2011.04.003 1064-7406/11/$ – see front matter Ó 2011 Elsevier Inc. All rights reserved. facialplastic.theclinics.com 230 Khavkin & Ellis melanocytes on genital skin. Melanin is produced from tyrosine by the enzymatic activity of tyrosine kinase and is stored in melanosomes. Melano- somes are transported along the dendritic processes of melanocytes to adjacent keratino- cytes, where they form an umbrella-like cap over the nucleus, protecting it from the injurious effects of UV light.3 The ethnic variations in pigmentation are attributable to the different activity of melano- cytes, not the difference in number of melano- cytes. With age, melanocyte density decreases by 6% to 8% per decade, with higher density of Fig. 1. The 3 layers of the skin: epidermis, dermis, and melanocytes in sun-exposed skin than in non- hypodermis. (Courtesy of A.D.A.M. Education, Atlanta, GA. Copyright Ó 2011 A.D.A.M., Inc.) exposed skin at all ages. This explains the gener- alized increase in pigmentation and simultaneous The basal layer is composed of a single layer of decrease in melanocyte density that often accom- 4 cuboidal cells, which rest on the basement pany aging. membrane. Melanocytes can be seen between Langerhans cells are antigen-presenting cells the basal cells of the epidermis. The basal cells derived from bone marrow. They make up 3% to 3 divide, giving rise to the next layer: the prickle 6% of all cells in the epidermis and are found cell layer or stratum spinosum. This layer is usually mainly within the spinous layer. The dendritic 3 to 4 cells thick and is composed of polygonal processes of Langerhans cells uptake antigens cells with preformed keratin.2 The desmosomal deposited on the skin, process them, and present attachments between the cells appear as small them to T lymphocytes for activation of the spines, giving rise to the name stratum spinosum. immune response. The number of Langerhans The stratum spinosum is succeeded by stratum cells increases during allergic reactions, such as granulosum, which is usually 1 to 4 cells thick contact hypersensitivity. With aging and chronic and derives its name from cytoplasmic keratohya- sun exposure, the number of Langerhans cells lin granules. The outermost layer of the epidermis decreases, which may play a permissive role in is stratum corneum composed of flattened kerati- the development of cutaneous carcinoma in indi- 5 nocytes that have lost their nuclei and cytoplasmic viduals who are elderly with sun-damaged skin. organelles.1 These keratinocytes are shed in the Merkel cells are found in the basal layer of the process of epidermal turnover. epidermis and in the epithelial sheath of hair folli- Melanocytes are derived from neural crest cles. Merkel cells migrate from neural crest to the cells and migrate into the epidermis where they skin and have similar chemical and structural produce melanin. They are distributed among the properties to an amine precursor uptake decar- 6 basal keratinocytes with the ratio of 1 melanocyte boxylation (APUD) cell. Merkel cells are associ- to 4 to 10 basal cells. This ratio varies with ated with sensory nerve endings in the skin and 4 anatomic location, with maximal density of may function as mechanoreceptors. Epidermal appendages Epidermal appendages are specialized epithelial structures located mainly in the dermis and hypo- dermis, but connected to the epidermis. They include pilosebaceous follicles, sweat glands, and apocrine glands. They play an important role in the epithelialization phase of wound healing. Pilosebaceous unit The pilosebaceous unit con- sists of hair, hair follicle, sebaceous gland, and arrector pili muscle (Fig. 3). It is distributed throughout the integument, absent only in palms and soles and portions of the genitalia. The hair follicle is composed of several segments: infundibulum, isthmus, lower follicle, Fig. 2. Layers of the epidermis (hematoxylin-eosin, and hair bulb. The topmost portion is the infundib- magnification Â40). ulum, extending down from the skin to the opening Aging Skin: Histology, Physiology, Pathology 231 Sebaceous glands are present in most areas of the body with the exception of palms and soles, with highest density of sebaceous glands found on the face. They consist of an outer layer of basal cells and several layers of lipid-laden sebocytes. Sebocytes disintegrate toward the center of the gland, thus forming sebum, which empties into the hair follicle via a short duct. Sebum provides emollients for the hair and skin. The secretions of the sebaceous glands are under the influence of Fig. 3. Pilosebaceous unit. androgen hormones. The gland activity increases shortly after birth and subsides in the first few of the sebaceous duct into the hair follicle. The postnatal months. At puberty, there is a new rise isthmus extends from the infundibulum to the in sebaceous gland activity associated with bulge, the site of insertion of the arrector pili muscle increased androgen output. Increased sebum into the follicle. The bulge contains stem cells of the production is a major factor in the pathophysiology hair follicle. Contraction of the arrector pili muscle of acne vulgaris.7 Sebum secretion declines with causes the hair to be pulled from an oblique to age by about 23% per decade in men and 32% a more vertical orientation in response to stimuli per decade in women.8 The size of the sebaceous from the sympathetic nervous system. Clinically, glands increases with age, despite decrease in contraction of the arrector pili muscle results in sebum production.9 This can result in large pores, slight elevations of the skin or goose bumps. The as seen with age. lower follicle extends down to the top of the hair bulb and the hair bulb is the terminal portion of Sweat glands The eccrine glands are the main the hair follicle, which envelops the follicular papilla. sweat glands in humans and play a vital role in The papilla is a dermal structure containing the process of thermoregulation. They are found a richly vascularized and innervated connective almost everywhere on the skin except the vermil- tissue and fibroblasts, important for hair growth.3 lion border of the lips and nail beds and have The hair bulb contains the matrix cells that give maximum density over palms, soles, axillae, and rise to the hair and melanocytes responsible forehead.3 With aging, the number and function for hair pigmentation. Permanent hair removal of eccrine sweat glands decrease. requires damage to follicular stem cells in the Each eccrine gland is composed of 3 parts: the bulge region of the hair follicle.