Mechanisms of skin aging

Skin is the largest organ in the human body in terms of surface area. The surface area of an adult's skin can reach up to 1.6 square meters, and its weight accounts for up to 6% of the body mass. The skin has several important functions, including:

•  Protective function
•  Respiratory function
•  Thermoregulatory function
•  Tactile function
•  Metabolic function
•  Covering function
•  Excretory function

The skin not only serves as a physiological barrier that separates the body from the external environment and protects against moisture loss but also plays a significant cosmetic role. A youthful and healthy appearance has an impact on a person's social status. Unfortunately, the most apparent signs of aging are often visible through the condition of the skin. The issue of skin aging has traditionally been of great concern, particularly for women. There has been and continues to be a constant interest in cosmetic methods and skincare products aimed at slowing down the aging process. Nowadays, daily expenses on cosmetics and pharmaceuticals targeted at combating aging constitute a significant portion of the average consumer's expenditure. Consequently, the demand for cosmetic products and services stimulates scientific progress and research in this field.

The aging process of the body begins from birth and is a normal physiological process. Skin aging is no exception. In the article "Fighting against Skin Aging" by Shoubing Zhang et al., 2018, the authors present up-to-date information on external and internal processes involved in skin aging. In this review, we will summarize the processes that occur during skin aging and the advancements in molecular and genetic research in this area.

Internal aging is an inevitable physiological process that leads to:

•  Thinning of the skin
•  Dryness
•  Fine wrinkles
•  Skin atrophy

External aging is caused by environmental factors such as:

•  Environmental pollution
•  Smoking
•  Poor nutrition
•  Solar UV radiation

All these external factors contribute to the appearance of:

•  Deep wrinkles
•  Loss of elasticity
•  Sagging
•  Roughening of the skin texture

Intrinsic aging of the skin refers to the chronological physiological changes that occur internally. The skin can be divided into sun-protected and sun-exposed areas. Sun-exposed areas are typically uncovered by clothing, such as the face, neck, hands, forearms, and feet. Sun-protected areas are those covered by clothing, such as the inner surface of the arm or other covered areas. The aging process of sun-protected areas is related to internal genetic or metabolic factors. The basal cell layer of the skin undergoes the most significant changes during the aging process. Aging in the basal cell layer manifests as a decrease in contact between the epidermis and the dermis, a reduction in the supply of nutrients to the epidermis, which inevitably leads to thinning of the epidermis. This process is called cellular aging.

Furthermore, in the aging dermis of sun-protected skin, there is a significant thinning of collagen, elastin fibers, oligosaccharides, and fibrillin (a glycoprotein involved in elastin synthesis), which affects the skin's ability to retain moisture. The production of procollagen (a precursor of collagen) decreases as well.

External aging of the skin (Extrinsic aging)

The first assumption about the negative effects of solar radiation on the skin was made in 1969 (Kligman et al., 1969). It is now established that UV radiation is the primary factor in the external aging of the skin, accounting for approximately 80% of facial aging manifestations. Prolonged exposure to solar UV radiation is the main factor in external aging and is called photoaging.

For photoaged skin areas, the accumulation of abnormal elastic tissue in the deep layers of the dermis is the main process. This pathological process is called solar elastosis. It involves an initial increase in elastin expression by 4 times, followed by the destruction and fragmentation of elastic fibers, known as elastolysis. The picture of external aging is further exacerbated by a decrease in microcirculatory function.

Recent scientific studies confirm that most factors contributing to skin aging are caused by external influences, while only about 3% of factors have internal mechanisms.

Molecular mechanisms of skin aging

The molecular mechanisms of skin aging include:

•  Oxidative stress;
•  DNA damage;
•  Telomere shortening;
•  MicroRNA regulation disruption;
•  Accumulation of advanced glycation end products;
•  Genetic mutations.

It is believed that reactive oxygen species (ROS) play a critical role in changes to the extracellular matrix of the skin during both natural and photoaging. For example, under the influence of UV radiation, cellular structures absorb energy, become activated, and produce increased amounts of oxidation products and ROS. These processes, in turn, initiate a chain of changes in the collagen fibers of the skin, ultimately leading to a suppression of collagen synthesis. The reduction of collagen levels in the skin inevitably leads to premature aging.

Another process influenced by ROS is telomere shortening. Telomeres are repeated segments of nucleotides (components of DNA and RNA) that protect the ends of chromosomes from degradation. Telomerase is an enzyme that adds telomere repeats to prevent shortening. With increased UV radiation and excessive ROS production, telomeres mutate and shorten, leading to aging and even death of skin cells.

Persistent exposure to UV radiation stimulates DNA mutations in skin cells, leading not only to premature aging but also to carcinogenesis. When DNA in skin cells absorbs photons of UV radiation, it undergoes nucleotide rearrangement, resulting in DNA strand defects. Recent research provides strong evidence for the effectiveness of using sunscreen to prevent DNA defects, which are the cause of squamous cell carcinoma and melanoma.

Premature aging is also caused by advanced glycation end products (AGE), during which collagen, proteins, lipids, and nucleic acids pathologically bind to sugar molecules (glucose and lactose) and accumulate in excess.

Special interest is given to genetic mutations (Makrantonaki E. et al., 2012), which are inherited and cause progeria – a type of premature aging that includes manifestations such as:

•  Accelerated aging of the skin with atrophy and sclerosis;
•  Poikiloderma;
•  Alopecia;
•  Premature thinning and graying of the hair.

Not all diseases caused by genetic mutations have been thoroughly studied. Research on genetic variations in the aging process is ongoing.

Prevention of diseases, a healthy lifestyle, proper nutrition, and skincare are essential components for maintaining skin health. The skin is not only about a presentable appearance but also about providing necessary physiological functions, making it one of the most important organs in the human body.

How can we achieve prolonged youthfulness of the skin?

How to combat the first signs of aging?

What are the modern scientific developments and recommendations for skincare?

Read about it in our article: "Modern Strategies for Combating Skin Aging".