How are wrinkles generated?
Ageing is a natural, inevitable and irreversible process that affects our health, including that of the skin. One of the most obvious signs of skin aging is wrinkles, which are folds and furrows that develop over time. By the way, you can click here to read an article where we talk about the theories of aging.
And beyond the fact that wrinkles are part of this aging process, their formation can be influenced by a series of intrinsic and extrinsic factors. In this article, we will explore in detail how wrinkles are generated, looking at the underlying causes and the biological mechanisms involved. In addition, we will give you some tips to take into account to improve skin health and increase the collagen matrix.
Causes of wrinkles
Given its strategic location at the body’s interface, the skin is subject to intrinsic (chronological) aging that is usually under genetic and hormonal influence and extrinsic aging caused by environmental factors, mainly UV radiation, smoking, diet, chemicals, trauma, etc. The effects of ultraviolet radiation on the skin are so powerful that they have a separate specific name called photoaging. https://doi.org/10.1016/j.jtv.2016.03.002
The ageing of photoprotected areas, such as the inner arm, is mainly due to intrinsic genetic or metabolic factors, while exposed areas of skin are also influenced by extrinsic factors, especially UV solar radiation. In areas protected from the sun, the most pronounced changes occur within the epidermis and mainly affect the basal cell layer. As a result, while as a person’s age advances, sun-protected aging skin becomes thin, finely wrinkled, and dry, while photo-aged skin is characterized by deep wrinkles, sagging, and roughness.
Among the most important biological processes involved in skin aging are alterations in DNA repair and stability, mitochondrial function, cell cycle and apoptosis, ubiquitin-induced proteolysis, and cell metabolism. One of the main factors that has been proposed to play an important role in the onset of aging is the physiological hormonal decline that occurs with age. However, hormones at specific levels may not only regulate age-associated mechanisms but also regulate tumor suppressor pathways that influence carcinogenesis. https://doi.org/10.1196/annals.1404.027
Main factors
The main factors and most significant causes include:
- Collagen and elastin degradation: Both are key proteins that provide structure and elasticity to the skin. With aging, the production of these proteins decreases, and existing ones degrade. This loss of structural support leads to the formation of wrinkles.
- Decreased production of hyaluronic acid: This important component of the skin helps to keep it hydrated and turgid. Over time, hyaluronic acid production decreases, leading to more dehydrated and wrinkle-prone skin.
- Exposure to ultraviolet radiation: chronic exposure to solar radiation is one of the main extrinsic causes of wrinkle formation. It damages the DNA of skin cells, inhibits collagen and elastin synthesis, and promotes the formation of free radicals, which contributes to premature skin aging and the development of wrinkles. Exposure to ultraviolet radiation is the main factor in extrinsic skin aging; it accounts for about 80% of facial aging. DOI: 10.1016/j.fsc.2005.04.004
- Lifestyle habits and environmental factors: among the habits to be corrected are smoking, poor diet, stress and lack of sleep. These are factors that can accelerate the skin’s aging process and increase the formation of wrinkles. Environmental pollution also plays a crucial role.
Biological mechanisms of wrinkle formation
The formation of wrinkles is the result of a complex interaction between various biological processes that affect the structure and function of the skin. Some of the key biological mechanisms include:
Intrinsic mechanisms
Oxidative stress
Endogenous oxidative stress results from an imbalance between the production of reactive oxygen species (ROS) and the skin’s antioxidant capacity to neutralize them. Excess ROS damages cellular structures, including DNA, proteins, and lipids, contributing to skin aging and wrinkle formation. Endogenous ROS can be produced from different sources, including the mitochondrial electron transport chain, proteins located in the endoplasmic and peroxisomal reticulum, the Fenton reaction, and enzymes such as cyclooxygenases, lipoxygenases, xanthine oxidases, and NADPH oxidases. DOI: 10.3390/biom5020545
Glycation
Glycation is a biochemical process in which glucose or fructose molecules bind to proteins such as collagen and elastin, lipids, or nucleic acids, resulting in the inhibition of the normal function of the target molecules forming advanced glycation end products (AGEs). Glycation is involved in both intrinsic and extrinsic aging. Long-lived proteins in the dermal matrix and cytoskeleton are particularly susceptible to glycation, resulting in tissue stiffness and reduced elasticity. DOI: 10.1111/exd.13076
Chronic cellular inflammation
Chronic cellular inflammation is an important factor in skin aging and wrinkle formation. The release of pro-inflammatory cytokines and the activation of proteolytic enzymes lead to the degradation of collagen and elastin, as well as dermal cell dysfunction, which promotes the formation of wrinkles. UV exposure triggers an inflammatory response in the skin, leading to the release of cytokines such as interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF). These cytokines promote the activity of neprilysin and matrix metalloproteinases, which further degrade the extracellular matrix and impair skin elasticity. DOI: 10.1046/j.1523-1747.2003.12136.x
Alterations in cell renewal
With aging, the ability of skin cells to renew and repair themselves decreases. This can lead to a decrease in the production of new dermal cells and a reduction in the regeneration of the extracellular matrix, which contributes to the formation of wrinkles and loss of skin firmness. Telomeres, which are repetitive nucleotide sequences that protect the ends of chromosomes, shorten with each cell division, ultimately leading to cellular senescence and a limited number of cell divisions.
Telomerase maintains telomere length and is crucial for cellular longevity. However, its activity decreases with age, contributing to the aging process. Modulation of telomerase activity presents a potential target for anti-aging therapies. DOI: 10.1155/2016/7370642
Extrinsic mechanisms
Mechanisms of DNA damage and repair
UV radiation causes direct damage to DNA, leading to the formation of cyclobutane pyrimidine (CPD) dimers. The skin’s ability to repair this damage decreases with age, resulting in the accumulation of mutations and cellular dysfunction. When DNA absorbs photons from UV-B rays, a structural rearrangement of nucleotides occurs. This produces defects in the DNA strands. DNA damage can be repaired in smaller species by removing the lesion using the enzyme photolyase, but higher cells in mammals and humans do not have this enzyme. It is achieved by the nucleotide excision repair pathway. Once the proteins in this pathway are deficient, DNA damage and premature aging of the skin will occur. DOI: 10.1038/jidsymp.2009.6
Contamination
The main chemical air pollutants that affect the skin are polycyclic aromatic hydrocarbons, volatile organic compounds, nitrogen oxides, particulate matter, cigarette smoke, heavy metals, and arsenic. These chemical pollutants can penetrate the skin and generate oxidative stress. This process exacerbates the breakdown of collagen and elastin, accelerating the formation of wrinkles. In the case of microplastics, they exhibit a high propensity to adsorb various toxic substances present in the environment. It poses potential health risks when ingested or inhaled through the human digestive and respiratory tract. In addition, they can serve as constituents of atmospheric pollutant particles, triggering a series of immune responses, such as oxidative stress. https://doi.org/10.1016/j.scitotenv.2023.165615
Smoking
The chemicals present in tobacco smoke reduce blood flow to the skin and deplete essential nutrients, such as vitamin C, which is crucial for collagen synthesis. This leads to premature aging and the development of wrinkles. On the other hand, reactive oxidants and free radicals from cigarette smoke cause oxidative stress or secondary oxidative events and inhibition of the body’s intrinsic antioxidant mechanisms. The chemicals present in cigarette smoke increase transepidermal water loss, degeneration of connective tissue in the skin, and upregulation of matrix metalloproteinases that degrade collagen and elastic fibers. https://doi.org/10.1016/S0039-6060(98)70167-9
Therapeutic Perspectives
As we have said before, wrinkles are a natural sign of aging, however, there are various therapeutic strategies aimed at preventing their formation or reducing their appearance. Some of these interventions include
Use of sunscreens
Protection from UV radiation through regular use of broad-spectrum sunscreens can help prevent sun damage and reduce the risk of premature wrinkles. Chemical sunscreens are the most widely traded sunscreens. The combination of two to six of the following active ingredients is typically used: oxybenzone, avobenzone, octisalate, octocrylene, homosalate, and octinoxate. Chemical formulations of sunscreen are usually alcohol-based, lipophilic, or a combination of both, which can facilitate the delivery of actives to the stratum corneum. Another type of sunscreen, called physical sunscreen, is applied to the surface of the skin to block and scatter ultraviolet radiation. In physical sunscreens, minerals, titanium dioxide, and zinc oxide are the main active ingredients. https://doi.org/10.1016/j.addr.2020.02.001
Anti-aging topical products
The use of creams and serums that contain active ingredients. Ingredients such as retinoids, antioxidants, specific peptides and hyaluronic acid. These can help stimulate collagen production, improve skin hydration, and reduce the visible appearance of wrinkles. https://doi.org/10.1007/s12325-022-02319-7
Oral supplements
The continuous intake of food supplements such as collagen powder, hyaluronic acid, vitamin C and various antioxidants, generate a reserve of essential nutrients to maintain good skin quality. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8944283/
Dermatoaesthetic procedures
These procedures, which include chemical peels, microdermabrasion, laser therapy, dermal fillers, and more, have proven effective in improving the appearance of wrinkles and rejuvenating the skin.
Bioidentical hormone replacement therapy
In addition to being used in the treatment of symptoms caused by menopause, hormone replacement therapy is used to slow the aging process of the skin. HRT improves skin thickness, collagen content, elasticity, and improves hydration.
Stem cell therapy
Advances in stem cell research offer potential to regenerate aging skin and improve its regenerative capacity. Stem cell-based therapies are being explored for their ability to rejuvenate skin by replenishing depleted stem cell populations. https://doi.org/10.1007/s00266-021-02353-w
Peptides and growth factors
Peptides such as collagen and elastin peptides, along with growth factors, can stimulate fibroblast activity and improve extracellular matrix production, which improves skin firmness and reduces wrinkle depth. https://doi.org/10.1080/02648725.2023.2199233
Exosomas
Exosomes are small extracellular nanovesicles released by cells. Its potential for use in cosmetics, skin care and tissue regeneration has been explored. The therapeutic value of exosomes lies in their ability to modulate the microenvironment of cells, regulate gene expression, and induce cell differentiation, which can have a positive impact on skin health. In cosmetic terms, exosomes have been used to reduce wrinkles, improve skin texture and hydration, and improve skin elasticity, as well as reduce inflammation and damage caused by UV radiation. https://doi.org/10.3390/cosmetics10020065
Healthy lifestyle
Adopting a healthy lifestyle that includes a balanced diet, regular exercise, stress management, and proper sleep habits can help maintain long-term skin health and youthfulness.
Salengei Options
Within our wide range of products that positively affect aging, there are three that we would like to highlight due to their specificity in skin aging.
- Procollagen Plus. Dietary supplement based on collagen, glucosamine, MSM, amino acids, plant extracts, vitamins and minerals, with sweetener that contributes to the formation of skin and bone collagen, the normal functioning of cartilage and connective tissue and the maintenance of bones in normal conditions.
- Revive Celular. Dietary supplement with fisetin, green tea, curcumin, reishi, resveratrol, quercetin, berberine, CoQ10, vitamin C, PQQ and astaxanthin that contributes to the protection of cells against oxidative damage.
- MorEPA. Highly concentrated fish oil-based dietary supplement: 1020 mg of Omega-3 and 1000 IU of Vitamin D per pearl.
Conclusion
The formation of wrinkles, being part of aging, is a multifactorial process that results from the interaction of intrinsic and extrinsic factors, as well as complex biological mechanisms. The factors named among the causes interact synergistically to contribute to the development of wrinkles through the degradation of collagen and elastin, the decrease in skin hydration and the generation of oxidative stress.
While wrinkles are an inexorable sign of aging, understanding the underlying causes and mechanisms involved can help develop effective strategies to prevent their formation or reduce their appearance. From a therapeutic perspective, there are various strategies to prevent their formation or reduce their appearance. These measures include the home and medical interventions discussed above, as well as the adoption of a healthy lifestyle.
Being able to deliver these successful one-off interventions through preventative and therapeutic approaches is what offers opportunities to maintain skin health and youthfulness over time.
As we always say, our disclosures and recommendations are in no way intended to prevent consultation with medical professionals, quite the opposite. The options offered here should be evaluated by your specialist and/or family doctor.
