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Introduction

The skin is the most superficial part of the body. The signs of ageing are most visible in the skin. Although, ageing skin is not a threat to a person, it can have a detrimental effect on the psychology of a person. A look into the causes of skin ageing, the available treatments and preventive measures for this inevitable change is important to help both the already aged, as well as, the youth.

This is a 4 part article in which:

1. Part 1 – Discusses the structure of skin and its different components
2. Part 2 – Discusses cutaneous ageing and its causes (current article)
3. Part 3 – Discusses the characteristics of ageing skin and the changes in skin appearance
4. Part 4 – Discusses products and treatments for skin ageing
   a) Sunscreen Agents
   b) Moisturizers
   c) Antioxidants
   d) Make Up
   e) Dermal Fillers
   f) Chemical Peels
   g) Botulinum Toxin
   h) Estrogen and Hormonal Treatments
   i) Plastic Surgery

Part 2 – Cutaneous Ageing and its Causes

Cutaneous Ageing¹

There are 2 primary skin ageing processes:‐

i) Intrinsic Ageing/Natural Ageing is caused either by telomere shortening, mitochondrial damage, and endocrine dysfunction. Intrinsically aged skin is smooth and unblemished and characterized by normal geometric patterns with some exaggerated expression lines. Histologically such a skin manifests epidermal and dermal atrophy, flattening of epidermal rete ridges, reduced number of fibroblasts and mast cells, increase number of collagen fibrils and increased ratio of collagen III to collagen I.

ii)Extrinsic Ageing by exogenous origin i.e. smoking, poor nutrition and solar exposure. These factors are responsible for premature ageing of the skin. Extrinsically aged skin that results from cumulative effect of lifelong ultraviolet radiation exposure on the exposed area of skin i.e. face, chest, arms comprise rhytides, pigmented lesions (lentigens and patchy hyperpigmentation) and depigmented lesions (guttate hypomelanosis). There is loss in tone and elasticity is also observed along with increased skin fragility, benign lesions (keratoses and telangiectases). Histopathology of photo aged skin is characterized by elastosis, epidermal atrophy and distinct alteration in collagen and elastic fibers. Severe photo aged skin would exhibit fragmented thickened and more soluble collagen fibers.

Causes of Ageing

Telomere Shortening^1,2

Telomeres, the specialized structures found at the ends of eukaryotic chromosomes, have come under increasing scrutiny and are now believed to play an essential role in the intrinsic ageing process at a cellular level. Intact telomeres are integral in extending the lifespan of cells. With age, telomere length shortens. This telomeric erosion has come to be seen as a gauge by which to measure ageing, a veritable internal ageing clock, and the basis for one of the presently favored theories on ageing.

One implication of this theory places ageing and cancer on opposite sides of the same coin. That is, telomerase, the cellular reverse transcriptase enzyme that stabilizes or lengthens telomeres, is expressed in about 85–90% of all human tumors but absent in many somatic tissues. Consequently, most cancer cells, unlike healthy ones, are not programmed for apoptosis, or cell death. In other words, the presence of telomerase is associated with telomere stability and tumourigenesis, its absence with telomere shortening and somatic tissue ageing.

Indeed, the natural, progressive shortening of telomeres may be one of the primary mechanisms of cellular ageing in skin. Telomeres and other cellular constituents also sustain low‐grade oxidative damage as a result of aerobic cellular metabolism, which contributes to intrinsic ageing.

Currently, there are no available topical skin care products, systemic drugs or other treatment options that target telomerase since experimental data does not adequately demonstrate that extending telomere length can be safely performed. One argument for eventual telomerase‐based therapies is the belief that inhibiting telomerase may also have antiproliferative and apoptosis‐inducing effects, not related to the role this ribonucleoprotein plays in shortening telomeres during cell division.

Mitochondrial Damage^1,2

The mitochondria are considered as the power house of the cell as they generate energy to the cell, by the multistep process called oxidative phosphorylation or electron transport chain. They are responsible for ATP production from ADP and an inorganic phosphate molecule. Along with this ATP production a free radical is also generated.

Free radicals are nothing but reactive oxygen species where the oxygen has unpaired electrons. Thus, the mitochondria is the site of the highest reactive oxygen species turnover in the cell. The bad effects of this reactive oxygen species are lipid peroxidation and alteration of gene expression pathway causing degradation on dermal protein collagen which in turn causes accumulation of elastin.

Endocrine Dysfunction²

It is observed that with age there is reduction in the production of hormones. Estrogen is one such hormone the production of which reduces with age and lower levels of estrogen is associated with skin ageing and telomere shortening. The effects of reduced estrogen level causes loss of elasticity, reduced water holding capacity, increased pigmentation and decreased vascularity.

Photoaging¹

Skin ageing caused by sun exposure can occur even before intrinsic ageing. The changes that are observed due to photoaging are leathery appearance with wrinkle formation, impaired wound healing, appearance of lesions on the skin such as actinic and seborrheic keratoses, cutaneous horns, skin cancer, pigmentary alterations such as lentigens and hyperpigmentation and the most prominent feature is elastosis. The ultraviolet rays from the sun causes skin damage and accelerate ageing of the skin.

There are 2 mechanisms by which the ultraviolet radiations act :‐

i) Induction of matrix metalloproteinases – Matrix metalloproteinases are a group of enzymes of subfamily proteinases that areresponsible for the degradation of collagen. The ultraviolet light affects the post translational modification of these dermal matrix proteins (such as collagen) and induces wide variety of an ever increasing family of MMP’s with proteolytic activity to degrade matrix protein. Thus, the induction of MMP’s plays major role in the pathogenesis of photoageing.

ii) Ultraviolet Induced Mitochondrial Damage ‐ Ultraviolet radiations can cause mitochondrial damage in three ways:

a) Mitochondrial DNA Damage: DNA is not just restricted in location within the nucleus but is also found in the mitochondria. The human mitochondrial DNA has a mutation frequency 50 folds higher than nuclear DNA. Ultraviolet rays can induce these mutations in the mitochondrial DNA. Thus being responsible in photoageing.

b) Production of Reactive Oxygen Species: The Ultraviolet radiations are capable of exciting electrons in the outermost shell of the oxygen atom to a higher energy level. This excitation can cause the oxygen molecule in cells to split into the oxygen free radical. The oxygen free radicals can be of various kinds such as the hydroxyl radical (which is the most common). These free radicals are known as reactive oxygen species. These reactive oxygen species can cause damage to the cell, in turn causing ageing.

c) Formation of uncommon D‐β‐ Aspartyl residues: UV radiations leads to the formation of D‐β‐ Aspartyl residues in the elastic fibers of the skin. These uncommon D‐β‐ Aspartyl residues have been reported in proteins of various elderly tissues.

Smoking³

Studies have shown that smokers look older than non‐smokers of the same age because smoking has an ageing effect on human skin, especially in the facial region. Mechanism of smoking induced ageing is not known, but invitro studies have shown that the tobacco smoke extract induces MMP‐1 and MMP‐3 mRNA in skin fibroblasts. However tobacco smoke has no effect on TIMP‐1 (Tissue Inhibitor of Matrix Metalloproteinases) and TIMP‐3 mRNA. In vivo studies have demonstrated that smoking induces MMP‐1 mRNA in the skin but has no effect on TIMP‐1 mRNA. These studies suggested that smoking showed multiplicative effect on facial ageing via the induction of MMP‐1.

Lifestyle

The lifestyle of a person can also contribute to the ageing skin. Factors such as lack of sleep, alcohol consumption, stress, improper diet, and reduced intake of water, can all lead to minor signs of ageing.

References

1. Skin ageing and its treatment, L Baumann; Journal of Pathology J Pathol 2007; 211: 241–251
2. Nutritional and Botanical Approaches to Antiaging, Chris D. Meletis, N.D., with Nieske Zabriskie, N.D. Alternative and Complementary Therapies, December 2006, 268‐274.
3. Elderly skin and its rejuvenation: products and procedures for the aging skin, Marcia Ramos‐e‐Silva et. al., Journal of Cosmetic Dermatology, 6, 40–50