Ageing is a universal and natural physiological process that is reflected by deterioration in the organism activity and result in age related health complications. Skin undergoes changes as well, particularly in its cellular activity and cellular environment. These changes result in the appearance of skin ageing signs including:

  • discoloration such as melasma,
  • facial wrinkles,
  • sallow skin,
  • reduced elasticity and strength “elastosis”,
  • thinning of the epidermis,
  • thinning of the lipid layer which causes skin dehydration and the effect known as “spider veins”.

Taking care of the skin and reducing its ageing process is very important since it affects the organism quality of life. People tend to be attracted to a young and healthy appearance as it reflects strong organism and good genes.

Physiological (chronological) ageing of the skin is associated with the accumulation of reactive oxygen forms that lead to the destruction of cell membrane via the oxidation of lipid molecules, genome damage and impairment of cellular function and cell turnover.

Photo aging (premature, external) occurs as a result of exposure to UV rays that damage the internal structure of the skin (collagen degradation and solar elastosis). UV rays stimulate what is known as oxidative stress condition related to the accumulation of reactive oxygen forms and decomposition of collagen and elastin which is manifested in the appearance of wrinkles, hyper pigmentation, rough and saggy skin.

At the present, modern perspective of skin ageing is related to biological processes classified as intrinsic and extrinsic factors.

Extrinsic ageing factors:
  1. Sun exposure is one of the main factors that lead to skin ageing since UV rays such as B (290–320nm) and A (320–400 nm) have been proven to penetrate the skin barrier and as in the case of UVA and IRA (770–1400 nm) (Schroeder P et al., 2008) it can reach up to the dermis and subcutis layers of the skin (Kligman LH, 1982).

The first to observe the effect of sun exposure on skin was the dermatologist Paul Gerson Unna who observed the dramatic changes in skin conditions among sailors at Hamburg seaport and in 1986 Kligman and Klingman coined the term photo ageing.

UV and IR rays can stimulate to a great extent the production of ROS (reactive oxygen species) which are responsible for the activation of mitogen-activated protein kinases and transcription factors such as (AP-1 and NF-k2) which decrease collagen synthesis. ROS are responsible to the oxidation of membrane lipids, DNA and proteins which lead to cellular damage. Besides, they are accountable for the degradation and disorganization of extracellular components that surround the cells such as collagen and elastin. Disruption and loss of extracellular components make skin lose its volume and the appearance of wrinkles and pale skin.

UV and IR rays can stimulate the transcription of pro-inflammatory cytokines such as (TNF-α, IL-1, IL-6 and IL-8) and nuclear transcription factor AP-1 which triggers the synthesis of matrix metalloproteinase (MMP) responsible for the degradation of natural collagen.

Beside sun exposure as an extrinsic factor leading to premature skin, smoking and air pollution can be linked to the same category.

  1. In 1969 Harry Daniel published an article “smooth Tabaco and wrinkled skin” stating that smokers look older than non smokers.At the present day it is well known that smoking lead to higher expression of MMP-I and MMP-3 which decompose collagen I and III (Kennedy et al., 2003).
  2. Air pollution contributes to the development of ageing signs as well, mainly wrinkles and pigmentation.Studies have shown that pollution is responsible for an oxidative stress since particles from traffic pollution can serve as carriers for organic chemicals and metals that are capable of localizing in mitochondria and generating ROS directly in it (Li N et al., 2003). Traffic pollution in big cities is responsible for an increase in pigment spots and mimic wrinkles.
Intrinsic ageing factors

Intrinsic factors include different mechanisms that deteriorate with age and have a great influence on health in general and skin in particular. These factors include mainly chronological ageing related to the accumulation of free radicals, reduction of human telomere length which shortens with every cell division as well as decline in growth factors, signal molecules (cytokine and chemokines) and hormones such as estrogen, testosterone, dehydroepiandrosterone (DHEA), and its sulfate ester (DHEAS) (Wespes et al., 2002) (Arlt, 2004).

  1. Both ageing processes dependent on the ROS (reactive oxygen species) level which is formed through several mechanisms related to the oxygen inhaled by the organism, ionizing radiation such as UV rays, stress, pollution and dietary deficiencies. Natural antioxidant protection is provided by enzymes, superoxide dismutase, catalase, and peroxiredoxins that decline rapidly with age.

ROS: reactive oxygen species are byproducts that form due to chemical reactions that involve oxygen. In aerobic organisms ROS are produced by mitochondria that consume oxygen and reduce it to produce water (Fig. 1).
producing ROS

Fig. 1

O2–, H2O2,and OH are examples of the byproducts and beside aerobic respiration by mitochondria they can result from phygocytic activity of the immune system that use oxidative products such as nitric oxide (NO), O2–, H2O2, OCl– to destroy bacteria and viruses.

Another major source of ROS are peroxisomes which responsible for oxygen utilization. They contain oxidative enzymes such as catalase and urate oxidase that remove hydrogen from organic substance and produce hydrogen peroxide “H2O2” mainly the reduction of fatty acids into acetyl CoA a process known as β-oxidation. Catalase then reduces hydrogen peroxide into water and oxygen (Fig. 2).


Fig. 2

Under certain condition some peroxides escape degradation and in addition to age related catalase reduced activity H2O2 will be more abundant in the body.

According to Free radical theory, reactive oxygen species resemble a great contributor to ageing process. ROS causes DNA damage, oxidation of proteins and specific enzymes as well as lipid peroxidation, this result in the damage of the cells and their extracellular environment.

Active oxygen is believed to cause more than 200 kinds of damages to human body, and they may become the causes of several diseases such as diabetic, arteriosclerosis, cerebral vascular accident (apoplexy), senile dementia, coronary artery disease (cardiac infarction), cerebral infarction, ischaemia, tumour (cancer), cataracta, atopic dermatitis, gastritis, pulmonitis, arthritis, inflammation, chemical disorder, pesticides poisoning, autoimmune disease, stress ulcer, HIV, Parkinson disease, periodontal disease, aging

Organisms in general have a defense mechanism against free radicals known as SOD (superoxide dismutase) which was discovered by McCord and Fridovich in 1969. The detoxification of the free radicals is carried by enzymes such as gluthathion peroxidase that change H2O2 into 2H2O and catalase that convert H2O2 into H2O +O2. Beside these important enzymes organisms use different vitamins such as Vit. E, C etc known as anti oxidants. Recent studies have shown the importance of low molecular weight Hyaluronic acid in reducing the effect of free radicals as it has ROS scavenging effect compared to gluthathion (Chunlin ke et al., 2011).

  1. Skin ageing is related as well to an unprevented factor known as “biological clock”. With every cell division, cell ages until it reaches a stage called senescence or apoptosis, this phenomenon is related to a terminal portion of the cellular chromosome known as the telomere. With every cell division this telomere shortens and an enzyme called telomerase is responsible for its maintenance. The telomere sequence protects the end chromosome from end to end fusion during cell division which is incompatible with normal cellular growth. On the other hand as telomere shortens the cell chromosomes will undergo end to end fusion which leads to cell death or apoptosis. The majority of cells have the capacity for about 60 to 70 postnatal doublings during their lifecycles, and thereafter they reach senescence, remaining viable but incapable of proliferation, for example 30 % of the telomere length is lost in fibroblasts during adulthood (Allsopp et al., 1992)
  2. Another important intrinsic factor that cause ageing is related to the deterioration in the level of growth factors and signal molecules such as Cytokines and Chemokines that control cellular activity, growth, and synthesis of essential molecules that are required for the cell and its surrounding medium. Sex hormones have a great influence on age process as well, for example estrogen stimulates the production of collagen, elastin (Zouboulis, 2000) and hyaluronic acid (Epstein, 1975) keeping skin firm and hydrated. Deterioration in the levels of these hormones may lead to sallow non-hydrated skin and the emergence of age signs. Approximately 30% of skin collagen is lost in the first 5 years after the menopause, with an average decline of 2.1% per postmenopausal year over a period of 20 years.
  3. The reaction of non-enzymatic glycosylation of biomolecules (glycation) is another major cause of age-related changes in the skin. UV rays and concomitant oxidative stress result in cross-linking of proteins with sugars which affect their function and lead to their accumulation in the skin.

Glycation of keratin, for example, results in the appearance of brown pigment age spots and decreases the transparency of the skin. In addition, decrease in the formation of cross-bridges, which link the dermal collagen and elastin, leads to the disruption of dermal structure; reduces skin turgor and elasticity, increases blood vessels fragility and the appearance of wrinkles. On the other hand, glycation of lysozyme leads to a significant reduction in the immune defense of the skin.

This vicious cycle closes with the glycation of superoxide dismutase enzyme, a major antioxidant, leading to the failure in defense against oxidative stress, and thus beginning a new glycation chain.

Accordingly only prevention of non-enzymatic glycosylation process can stop the irreversible glycation – expression of age-related changes in the skin.