Skin

A Natural History

UNIVERSITY OF CALIFORNIA PRESS

Contents

skin laid bare

It isn't good to take for granted something as important as skin. Take a moment and imagine the following scene. You're standing in the moist, shadowy heat of an orchard in the late afternoon of a summer's day. You are able to stand outside in comfort without overheating, thanks to your skin's ability to regulate your body temperature and shield you from ultraviolet radiation. Only a few beads of sweat on your brow and upper lip betray the fact that your skin is working to keep you cool. As you flick away the fly that tried to settle on your face, you don't give a thought to the way your skin is protecting you from the microorganisms on the insect's feet and snout.

You have your eye on a peach dangling from a branch above your head, and you want to pick it and eat it. As you reach up toward that lovely peach, you're distracted again by the fly, and the back of your hand scrapes against the snag of an old branch. Thanks to your skin's fairly tough surface, the scrape isn't a problem. A welt starts to rise in a few minutes, but your skin is unbroken because its outermost layer is quite scuff-resistant. You reach up again, and the elastic properties of the skin on your arm and trunk allow you to stretch effortlessly until, on tiptoe, you touch the peach. As you grasp the fruit, you squeeze it ever so slightly and register its subtle softness through the exquisitely sensitive pressure sensors in the skin of your fingertips. It is ripe. As you pull the peach off the tree, the temperature sensors in the skin of your hand let you appreciate its slight warmth. As you lower your arm, the stretched skin of your arm and trunk returns instantly to its resting shape.

You bring the peach to your nose and smell it, and then brush it gently against your cheek, enjoying the feeling of the soft fuzz against your face. Your sensitive facial skin, with its high density of delicate touch sensors, is transmitting information about the texture of the peach to your brain. Just as you prepare to bite into the fruit, an annoying tickle at your ankle disturbs your reverie, and you realize that a mosquito has just bitten you while you were so pleasantly distracted with the smell and feel of the peach.

Your skin and its wide-ranging capabilities made the various parts of this scenario possible. To understand how this is so, an introductory tour of human skin, exploring its structure and its essential functions, is in order.

One of the most striking features of human skin is that it is basically naked; in this way it differs from the skin of most of our warm-blooded relatives. The ancestors of birds and mammals evolved fine, threadlike appendages on their skin—feathers and hairs, respectively, which regulate heat interchange and also help to prevent water loss and mechanical trauma. Lacking such protection, human skin had to undergo numerous structural changes to give it strength, resilience, and sensitivity. Our skin is not perfect, but it does a remarkably good job. Our fabric doesn't wear out, our seams don't burst, we don't spontaneously sprout leaks, and we don't expand like water balloons when we sit in the bathtub.

Some of the most important properties of skin are related to sunlight. In humans, the skin and the pigments it contains selectively filter the ultraviolet radiation emanating from the sun. Our skin has the amazing ability not only to serve as a protective shield against the damaging effects of sunlight but also to utilize some of that same sunlight to the body's advantage, by beginning the process of producing vitamin D right there in the skin. Thus our skin, like so many other parts of the body, is a compromise hammered out at the negotiating table of evolution. Its complex properties reflect a balance, brought about through natural selection, between conflicting needs—in this case, protection against harmful solar radiation and production of an essential vitamin.

Skin is made up of layers with different physical and chemical properties. This laminar, or layered, construction gives the skin its resistance to abrasions and punctures and allows it to avoid absorbing most substances. The skin's two major layers, the epidermis and the dermis, differ remarkably in their composition and function (figure 1). The skin also includes special types of cells that insinuate themselves into the skin during early embryonic development. These aptly named immigrant cells play varied and important roles in protecting the skin, as we'll see later in the chapter.

The skin's outermost layer, the epidermis, shields us from environmental oxidants and heat, while it also resists water, abrasion, stains, microbes, and many chemicals—a list of qualities that makes the epidermis sound more like a revolutionary new type of carpeting than a natural material. It is all the more astonishing, then, that these useful attributes are found in a self-renewing layer only about one millimeter thick, which continuously performs all its functions despite being in a constant state of turnover, with its outermost cells being shed as they are replaced from below. The epidermis is composed mostly of a specialized type of epithelium consisting of multiple layers, or strata, of flattened cells. (An epithelium is a covering of any external or internal surface of the body.) Because these cells contain high concentrations of the protective protein keratin, this epithelium is known scientifically as stratified keratinizing epithelium.

The very surface of the epidermis is its most remarkable layer, the stratum corneum (figure 2). The stratum corneum is sometimes called the epidermal horny layer because it consists of a relatively thin sheet of dead, flattened cells with a smooth, fairly tough, and water-resistant surface. The only things that interrupt its surface are hair follicles, the pores of sweat glands, and parts of some of the so-called immigrant cells that help to form the complex mosaic of the skin. The skin's effectiveness as a barrier against environmental insult of all kinds, especially oxidative stress such as ultraviolet radiation (UVR), ozone, air pollution, pathological microorganisms, chemical oxidants, and topically applied drugs, depends primarily on the integrity of the stratum corneum.

One of the ways the skin defends itself against some environmental stressors is to become thicker. When the skin is repeatedly exposed to UVR, for instance, cell division increases in the deepest layer of the epidermis, the stratum basale, which is the source of epidermal cells; and, as a result, the stratum corneum thickens. If the stress, whether external or internal, is extreme—too much UVR, too much heat, a corrosive chemical such as acid, some diseases or genetic problems—the stratum corneum can cease to be an effective barrier. This can have disastrous results if a large area of the skin is affected.

Keratinocytes, the main types of cells found in the epidermis, are made up of proteins called keratins. They are responsible for the strength, resistance, and stretchability of the skin's surface. Within keratinocytes, filaments of keratin are embedded in a gelatin-like matrix, and layer after layer of these cells build up from below to make up the epidermis. Between the cells, a substance rich in proteins and lipids fills the narrow spaces. The elasticity and imperviousness of the epidermis, especially the stratum corneum, result from its "brick and mortar" construction, that is, the tight and strong physical interconnections between adjacent cells and the protein and lipid material between them. In people with dark skin, the keratinocytes also contain flecks of the pigment melanin ("melanin dust"), which provide another layer of protection against UVR.

Scientists have long thought that human epidermis is unique because it does such a good job of protecting us even though we are effectively hairless. But the genetic basis for that uniqueness had not been appreciated until the past few years. One of the ways in which the genetic makeup of humans varies from that of our closest relatives, chimpanzees, is in the genes determining the structure of the epidermis. The recent sequencing of the chimpanzee genome has revealed that one of the few areas of the genome where humans and chimps differ significantly is in a cluster of functionally related genes that regulate the differentiation of the epidermis and contribute to coding the proteins that make up the keratin-rich layer of the skin. At least as far as primate skin goes, our epidermis is tough stuff.

The immigrant cells in the epidermis are a diverse lot that work with the other cells in the skin. They migrate into the skin from other parts of the body during early development to provide special physical and chemical protection against potent environmental agents such as UVR, disease-causing microorganisms, and dangerously high physical pressures. Although they are developmental interlopers, the immigrant cells don't in any way weaken the physical fabric of the skin. There are three main types of immigrant cells in the epidermis. Melanocytes (shown in figures 1 and 2) produce the skin's primary pigment and natural sunscreen, melanin. These cells migrate to the skin from a position flanking the spine during early embryonic development. Once they arrive, they set up shop near the interface of the dermis and the epidermis in order to manufacture melanin. Some people produce a lot of melanin in their melanocytes, whereas others produce only a little, depending on the amount of UVR present in the environment of their ancestors. Skin color, which is determined by the activity of melanocytes and their manufacture of melanin, has evolved under the close watch of natural selection.

Two other types of immigrant cells are also important. Langerhans cells are specialized cells of the immune system that respond to foreign substances coming in contact with the skin. They constitute the body's first line of defense against bacteria and viruses that land on the skin. Merkel cells are associated with the ends of sensory nerves in the skin, where they appear to assist in the transfer of mechanical signals from the skin to sensory nerves and then on to the brain. Merkel cells, which are common on the smooth skin of our fingertips and lips, contribute to our finely discriminating sense of touch. They are also of great importance to our furred and feathered relatives: in mammals and birds, Merkel cells occur in the collars of cells that support hair and feather follicles, including those surrounding the sensitive whiskers of dogs, cats, and rats.

Probing beneath the epidermis, we reach the second of the skin's two primary layers, a thick layer of dense connective tissue called the dermis. This is the layer that really imparts toughness to skin. It is pliable, elastic, and has considerable tensile strength. Most of the thickness of our own skin—and most of the thickness of the hide of any animal—comes from the dermis. Its thickness, in addition to its chemical and physical properties, helps to insulate the body and makes the skin resistant to mechanical injury. Leather is composed mainly of tough animal dermis that has been tanned so that it will be more pliable.

The dermis is a composite tissue that gets its strength and toughness from a combination of collagen fibers and elastin fibers. These fibers are maintained in a gel composed of salts, water, and large protein molecules called glycosaminoglycans. The primary cells of the dermis are collagen-rich cells known as fibroblasts. Collagen, which constitutes 77 percent of the dry weight of skin, accounts for most of the tensile strength of the skin and for some of its ability to scatter visible light (figure 3). Collagen acts just the way it looks, like tough little ropes of protein holding the dermis together. Interwoven with the collagen is a network of abundant elastin fibers that restore the skin to its normal configuration after stretching.

The production of collagen and elastin fibers slows down as we get older, and it is adversely affected by UVR from excessive sun exposure. Many products on the beauty market today claim to stimulate production of these materials to keep skin looking young. But there is only so much that creams, treatments, and "cosmeceuticals" can do to change the appearance and composition of skin, especially when people have caused irreparable damage through their incautious behavior in the sun. Many of the processes in the skin that control the production of collagen and elastin are governed by internal mechanisms of cellular aging that are not affected or are only weakly affected by what we apply to the skin's surface.

Amid the complex tangle of connective tissue fibers in the dermis, we find a branching network of blood vessels, an extensive network of nerves, numerous sweat glands, and an assortment of hair follicles, hair-raising arrector pili muscles, and oil-producing glands (refer back to figure 1). The blood vessels are critical because they supply the appetites of the sweat glands, the hair follicles, and the rapidly multiplying cells in the lowest layer of the epidermis. The density of blood vessels varies over the body's surface. They are especially concentrated on the head, for instance, where temperature regulation is particularly important to protect the brain and where the hair follicles of the scalp require good nutrition from a rich blood supply so that hair can grow. Blood vessels are also quite dense in areas where the skin must be kept moist by sweat and sebaceous (oil-producing) glands—for example, on the palms of the hands, the soles of the feet, and the nipples. In addition, blood vessel density is related to different postures. In both humans and primates, some of the densest concentrations of blood vessels in the body are found on the bottom of the buttocks, supplying the skin in this area with blood so that it does not deteriorate when we sit for long periods. In some of our close primate relatives, the skin around the female genitals is richly supplied with blood vessels, which permit the skin to become engorged with fluid when the animals are sexually receptive, creating puffy pink sexual swellings that are highly attractive to males.

The blood vessels of the dermis carry red blood cells, which derive their color from hemoglobin. Hemoglobin is a pigment that is bright red when it is carrying oxygen to cells and a dull reddish-blue after it has discharged its ferried oxygen and is heading back to the heart and lungs. Hemoglobin is one of the skin's main pigments, but it is most visible in people who have relatively little of the dark brown melanin pigment in their skin. Rosy cheeks and blue veins are more evident in people with light skin than in those with dark skin. The painfully bright red appearance of sunburned skin actually results from an increase in the number and diameter of the tiny blood vessels in the skin as well as an increase in the blood flow through each of these vessels. Sunburned skin feels hot to the touch because it is infused with blood and because it is mounting a hot and vigorous inflammatory response in order to repair the damage caused by UVR.

The nerves of the dermis are highly complex because the skin is one of the body's main sensory portals. Skin contains several specialized types of receptor cells, which send signals to the central nervous system about the external environment and the state of the skin. These include two types of temperature receptors, diverse mechanical receptors associated with both hairy and smooth skin, and an important group of pain sensors that specialize in detecting potentially dangerous physical stimuli or the presence of injury or inflammation. Although this formidable battery of receptor cells is extremely important, their evolutionary history is not yet well known.