Skin aging is characterized by processes such as wrinkle formation, loss of elasticity, and a rough appearance. This aging process is associated with phenotypic changes in cells as well as changes in the extracellular matrix (structures such as collagens and elastin). Here are some treatment strategies to prevent or reverse skin aging.
As reducing agents, antioxidants can reduce skin aging by neutralizing free radicals that have already formed. Free radicals activate the MAPK pathway and increase the production of MMPs that degrade collagen. This can be stopped by antioxidants such as vitamin C and vitamin E, antioxidant enzymes such as catalase, glutathione peroxidase, or coenzyme Q10. Some plants are natural sources of antioxidants, such as aloe vera and green tea. An example is epigallocatechin gallate (EGCG), a type of catechin in green tea, it prevents skin aging via the EGFR pathway in a mouse model, and shows a better structure than the control. In addition, N-acetylcysteine, a precursor to glutathione,
However, it is important that some researchers suggest that antioxidant supplements do not have anti-chronic disease-preventing effects, and that too much beta-carotene and vitamin A and E supplementation is potentially harmful, especially in well-fed populations, and that the optimal source of antioxidants is diet. not supplements. Previous research has shown that EGCG induces DNA death and damage in human lung and skin tissue through a reduction mechanism. The goal of antioxidant therapy is to restore oxygen homeostasis, not to completely eliminate all oxidants, as this may prevent the body from working properly. Therefore, for the clinical use of antioxidants, a physician should first evaluate the patient’s condition before issuing a prescription. The effect sought is not to completely inactivate all ROS,
Stem cell therapy.
Stem cell transplantation is a promising treatment for skin aging. Fat cell transplantation can improve the quality of the recipient’s skin and increase its volume. Further experimentation shows that Fat-Derived Stem Cells (ADSCs) are associated with skin regeneration during aging. In recent clinical trials, autologous adipose tissue transplantation restores aged skin and increases its volume in 50-year-old recipients. The data show that ADSCs produce growth factors such as VEGF bFGF TGF-beta1, TGF-beta2, HGF, KGF, PDGF-AA, and PGF, demonstrating that ADSCs can affect surrounding cells through these hormones. It appears that ADSCs can transdifferentiate into other skin stem cells by expressing the marker p63 after transplantation.
Retinoids are chemicals similar to vitamin A. Tretinoin is the first retinoid approved for clinical use. The introduction of tretinoin inhibits AP-1, thereby suppressing MMP and collagen degradation is stopped. An increase in the thickness of the epidermis and fibrils is observed, and internally aged skin may benefit from retinoid application.
Hormone replacement therapy.
In addition to treating the symptoms of menopause, hormone therapy can be used to slow down skin aging. Hormone replacement therapy increases skin thickness, collagen content, elasticity and hydration. However, some studies show that this therapy may increase the risk of breast cancer.
Although activation of telomerases would be an ideal way to reverse skin aging, and the high degree of expression of reverse transcriptase telomerase (TERT) in skin fibroblasts and keratinocytes induces a markedly increased proliferative capacity, but also increases the risk of carcinogenesis.
Since it is currently technically impossible to revert glycated proteins to their original state, the main strategy now is to prevent glycation. The problem is that the diet provides not only sugars such as glucose and fructose, but also formed Advanced Glycation Products (AGEs), especially grilled, fried, and toasted foods are high in AGE, while water-based foods contain little. Thus, low sugar food cooked in water would reduce the influence of external AGEs and the production of glycated proteins. In the future, finding drugs capable of de-glycation would be groundbreaking.
Some scientists believe that certain herbs and spices such as cinnamon, oregano, piment, and cloves can reduce fructose glycation. Some unions, incl. α-lipoic acid, carnitine, taurine, carnosine, flavonoids, bentopothiamine, alpha-tocopherol, niacinamide, pyridoxal, sodium selenate, riboflavin, zinc and manganese are associated with the inhibition of AGE formation. More research is needed to confirm these findings and demonstrate their inhibitory mechanisms.
Currently, therapies targeting HGPS are under investigation. Since the farnesyl group in the mutant protein progerin is considered the most important toxic component, the original therapies were designed to prevent farneling. The farnesyltransferase inhibitor lonafarnib has been used in clinical trials to heal 25 HGPS patients for 2 years, inducing better vascular health, bone structure and audiological status. Another strategy used a combination of two compounds, statins and an aminobisphosphate, efficiently inhibited both farneling and geranylgerylation of progins and prelamin A, and reduced aging-like effects in the Zmpste24 mouse model such as growth prevention, hair loss and bone defects. Clinical trials of the same study have been conducted, but the results are yet to be published. Other therapies not targeting the farnesyl group have also been proposed. Treatment of HGPS fibroblasts with rapamicin reverses premature aging and lobulated nuclei by increasing progerin lumen through macroautophagy pathways. In addition, the antioxidant sulforaphane helps to increase the progerin clearance through autophagy and reverses the cellular symptoms of HGPS. A tiny molecule known as remodelin is shown to help repair nuclear architecture, reduce DNA damage, and reverse HGPS cell proliferative defects. Retinoids are another compounds capable of reversing aging in HGPS patients. the antioxidant sulforaphane helps to increase the clearance for progerins through autophagy and reverses the cellular symptoms of HGPS. A tiny molecule known as remodelin is shown to help repair nuclear architecture, reduce DNA damage, and reverse HGPS cell proliferative defects. Retinoids are another compounds capable of reversing aging in HGPS patients. the antioxidant sulforaphane helps to increase the clearance for progerins through autophagy and reverses the cellular symptoms of HGPS. A tiny molecule known as remodelin is shown to help repair nuclear architecture, reduce DNA damage, and reverse HGPS cell proliferative defects. Retinoids are another compounds capable of reversing aging in HGPS patients.
For HGPS patients, the most important thing is to extend life, so most strategies are not focused on the skin.
The mechanisms of inflammation are poorly understood, so treatments are yet to be developed. Treatment of human fibroblasts using UV absorbing compounds, mycosporin-like amino acids (MAAs) prevents expression of the COX-2 gene, the expression of which is typically increased during inflammation. Moreover, expression of skin aging proteins is significantly decreased after MAA therapy. Some of the substances previously mentioned, such as vitamins A, C, D, E and green tea, also prevent inflammaging.
Despite these therapies, the best way to prevent skin aging is still to prevent external skin aging factors.
Department of Histology and Embryology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China
Central laboratory of Molecular and Cellular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China
State Key Lab of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China