The role of elastin and collagen in cutaneous aging: intrinsic aging versus photoexposure

Journal of Drugs in Dermatology, Feb, 2008 by Jouni Uitto

Abstract

Cutaneous aging occurs through 2 biologically distinct processes: intrinsic and extrinsic aging. The first is a naturally occurring process that results from slow tissue degeneration. In human dermis, intrinsic aging is characterized by 3 features: atrophy of the dermis due to loss of collagen, degeneration in the elastic fiber network, and loss of hydration. In contrast to intrinsic aging, extrinsic aging is due to environmental factors. Since ultraviolet (UV) exposure is the principal cause of extrinsic aging, it is often referred to as photoaging. At the microscopic level, the distinguishing feature of photoaging is a massive accumulation of elastotic material in the upper and middle dermis, a process termed solar elastosis. Using recombinant DNA technology, it has become possible to demonstrate that UV radiation can activate the human elastin promoter. This provides a mechanism for enhanced elastin biosynthesis, which contributes to the clinical and morphologic changes observed in photoaged skin.

Introduction

Cutaneous aging is a complex biological process associated with disruption of the physical integrity of the skin. The process has 2 components--intrinsic and extrinsic aging--that act independently. Intrinsic aging, sometimes called "innate" aging, is a natural process that is the result of an accumulation of irreversible age-associated degenerative changes. The effect of intrinsic aging on the skin is probably not unlike the effect of aging on the internal organs. Superimposed on this intrinsic component is extrinsic aging, which is primarily due to photodamage caused by ultraviolet (UV) irradiation of unprotected skin.

[FIGURE 1 OMITTED]

From a clinical standpoint, the 2 forms of cutaneous aging can be distinguished by comparing the sun-damaged face with another part of the body that has not been chronically exposed to the sun (eg, the underside of the arm) (Figure 1). Innate aging of the skin is typically characterized by very fine wrinkling, atrophy of the dermis, and a loss of subcutaneous adipose tissue. This is in sharp contrast to sun-damaged skin, which shows coarse wrinkling and furrowing along with an apparent thickening of the skin. These features are largely due to a phenomenon known as solar elastosis, in which elastotic material accumulates in the dermis.

A number of mechanisms have been proposed for the degenerative changes of innate aging in skin and other tissues. One theory holds that as tissues and cells become older, changes occur in their gene expression profile. Not only do the amounts of protein change, but aging cells also begin to manufacture abnormal proteins. In this context, the cutaneous proteins that appear to be most affected by the process of intrinsic aging are extracellular matrix proteins, primarily collagen and elastin.

There are at least 4 groups of extracellular matrix macromolecules required for normal skin physiology. Collagen and the fibers formed from it impart tensile properties to skin, allowing skin to serve as a protective organ against external trauma. Collagen is the most abundant of the extracellular matrix proteins; type 1 collagen accounts for approximately 80% of the dry weight of the dermis. (1) Fibers formed from the protein elastin provide elasticity and resilience, and they confer the "snap-back" properties to normal skin. A third category of cutaneous extracellular matrix proteins are noncollagenous glycoproteins. These are less abundant than collagen and elastin, but they play an important role in cellular adhesion, cellular motility, and other biological functions needed to maintain the physiology of human skin. Finally, there are the glycosaminoglycan/proteoglycan complexes. These macromolecules, which include hyaluronic acid, are a minor component of normal human skin, making up only 0.1% to 0.3% of total dry weight, yet they play a critical role by providing hydration. (1) Approximately 60% of the total weight of the dermis is water, retained largely as a result of the water-absorbing capacity of these macromolecules, as glycosaminoglycans can bind up to 1000 times their volume in water. (1)

As skin naturally matures from that of the newborn to that of an elderly person, it undergoes a number of structural changes. Newborn skin has an abundant collagen meshwork, accompanied by an intact elastic fiber network, and significant amounts of hyaluronic acid which provides a high degree of hydration. By contrast, naturally aged skin shows signs of dermal atrophy, primarily due to a loss of collagen. There is clear degeneration of the elastic fiber network, so that the resilience of the skin is lost, (2) and there is a loss of hydration due to changes in the glycosaminoglycan macromolecules. (3)

Collagen Metabolism in Aging Skin

Intrinsic aging has a dramatic effect on the network of collagen fibers of human skin. The quantitative changes are reflected by changes in collagen biosynthesis, which shows a steady decline up to about the third or fourth decade of life (Figure 2). (4) After that, collagen biosynthesis remains at a level that is too low to allow mature skin to repair and replace the collagen that has been lost as part of the degradative, age-associated process.