Aging of the Skin

Extrinsic and Intrinsic Aging

Aging of the skin can be broken down into two categories, intrinsic and extrinsic aging.  Intrinsic aging is age dependent deterioration or endogenous “wear and tear” of the skin’s structure and functions and accounts for 10% of total aging.  Extrinsic aging is damage and deterioration of the skin as a result of external factors such as UV radiation, stress, diet, lifestyle, and pollution and other environmental pollutants and accounts for 90% of total aging.  It is a combination of extrinsic and intrinsic aging factors that leads to the complex changes seen in the skin biochemically and morphologically as a person ages.  In this section, we want to consider what is happening underneath the skin that leads to the characteristic signs of aging.

Oxidative Damage

One of the primary causes of aging is oxidative damage.  One of the most widely publicized agents of oxidative damage is the free radical.  Free radicals are highly reactive chemical species with an unpaired electron that belong to the Reactive Oxygen Species (ROS) family. In seeking to pair this electron, free radicals cause much cellular damage, especially to collagen, elastin, and other proteins in the skin.  In the Free Radical Theory of Aging, it was postulated by Dr. Denham Harman that aging is a result of these free radical reactions that are associated with the environment, disease and the intrinsic aging process.  Exposure to UV radiation increases the number of free radicals present in the cells and the oxidative damage that occurs.  The damage to the proteins, collagen and elastin, in the skin affects the structure and appearance of the skin, specifically in the dermal layer.  The decrease in these proteins lead to a collapse in the structure resulting in thinning of the skin and appearance of wrinkles.

Besides free radicals, there are also other ROS that damage the skin.  It has been seen that ROS inactivate tissue inhibitors of metalloproteases and induce the synthesis and activation of matrix-degenerating metalloproteases (MMPs). MMPs are enzymes present in the skin that are responsible for breaking down and recycling damaged extracellular matrix.  The extracellular matrix is composed of the proteins collagen and elastin that act as the physical support of the skin cells and are responsible for the firmness and elasticity of the skin.  These enzymes play a key role in keeping the extracellular matrix healthy by breaking down any damaged molecules in the matrix.

The action of these enzymes are controlled by the presence of MMP inhibitors.  However, the ROS generated by UV radiation throw off this equlibrium by inactivating the MMP inhibitors.  This results in excessive activity of the MMPs breaking down the collagen and protein and resulting in a collapse of the extracellular matrix.  The collapse of the extracellular matrix is outwardly manifested in the skin’s appearance as the fine lines and sagging.

Glycation

Oxidative damage is only one of the mechanisms that need to be considered in the complicated process known as aging.  Glycation is the process where a glucose or aldehyde molecule is combined with a skin protein resulting in glycosylated proteins.  These proteins are generally more susceptible to damage caused by free radicals and can also become cross-linked with one another.  The cross-linking of these proteins result in large and harmful molecules called Advanced Glycation End-products (AGEs).  The accumulation of these end products result in hyperpigmentation commonly known as age spots.  AGEs cause the deformation of protein structure and perpetuate damage to the skin collagen, elastin and intracellular matrix and also increases the death rate of the fibroblasts through apoptosis.

DNA Damage

Besides damaging the protein structures in the skin cells, DNA is also affected by the aging process.  Damage to DNA is a result of both intrinsic, age-related factors such as replication errors as well as extrinsic factors such as UV radiation.  UV radiation, UVB in particular, is known to induce photoproducts in DNA.  These photoproducts become DNA-photolesions that can result in mutagenesis, cell death, or the initiation of carcinogenesis.

Generally, these lesions in the DNA are repaired.  However, as a person ages, the ability to repair this DNA damage decreases resulting in mutations of the DNA which could eventually lead to cancerous cells.  Damage to the DNA also affects the cell’s ability to perform its differentiated function.  UV radiation also generates reactive oxygen series (ROS).  These ROS are highly reactive and can cause much cellular damage.

The biological processes occurring in the body are very fine-tuned and balanced.  Anything that throws of this balance can lead to a deterioration of the function and structure of the human skin.  Some of the functions that begin to decline are cell replacement, barrier function, chemical clearance, and DNA repair.  Within the skin, the fat cells begin atrophy or diminish, the rate of cell division decreases and the dermis begins to thin out, and the collagen and elastin network start to unfold resulting in thinning of the skin, loss of elasticity and decreased metabolic activity.  As previously stated, 90% of aging comes from extrinsic factors, age-independent factors.  Knowing these mechanisms that are occurring allow us to address, prevent, treat, and restore the function and structure of the skin.