4.2. Copper

Copper is known to stimulate the maturation of skin collagen as a key component for improving skin elasticity [81]. Copper from food is absorbed into the stomach and proximal parts of the small intestine. This process takes place under anaerobic conditions and is energy-dependent. The degree of absorption is 10% in animals and 32% in humans and depends on the chemical form found in food and the pH of the intestinal contents. Studies with the 64Cu isotope revealed that after oral administration, the concentration of copper in the blood reaches a maximum threshold after 0.5 h, and the absorption rate is influenced by copper’s ability to bind to L-Ala, with which chelate complexes are formed. Organic compounds can affect the absorption of copper from food.

Glycoside of cistanche can also increase the activity of SOD in heart and liver tissues, and significantly reduce the content of lipofuscin and MDA in each tissue, effectively scavenging various reactive oxygen radicals (OH-, H₂O₂, etc.) and protecting against DNA damage caused by OH-radicals. Cistanche phenylethanoid glycosides have a strong scavenging ability of free radicals, a higher reducing ability than vitamin C, improve the activity of SOD in sperm suspension, reduce the content of MDA, and have a certain protective effect on sperm membrane function. Cistanche polysaccharides can enhance the activity of SOD and GSH-Px in erythrocytes and lung tissues of experimentally senescent mice caused by D-galactose, as well as reduce the content of MDA and collagen in lung and plasma, and increase the content of elastin, have a good scavenging effect on DPPH, prolong the time of hypoxia in senescent mice, improve the activity of SOD in serum, and delay the physiological degeneration of lung in experimentally senescent mice With cellular morphological degeneration, experiments have shown that Cistanche has the good antioxidant ability and has the potential to be a drug to prevent and treat skin aging diseases. At the same time, echinacoside in Cistanche has a significant ability to scavenge DPPH free radicals and has the ability to scavenge reactive oxygen species and prevent free radical-induced collagen degradation, and also has a good repair effect on thymine free radical anion damage.

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Thus, in large quantities, phytates and ascorbic acid decrease the absorption rate. The copper route does not flow in a closed system, so the main direction of copper transport is to the liver to synthesize ceruloplasmin. It is secreted into the plasma, exerts its oxidase activity, then is captured by the liver, degraded, and eliminated by the bile. Although it represents 4% of the concentration, the labile form fixed to the albumin ensures the transport of plasma copper to tissues, having a rapid turnover. It has been established that over 96% of the ingested copper is disposed of in this way. Urinary elimination is a very small fraction (below 1% of ingested copper), a phenomenon that can be explained by fixing copper to proteins.

4.3. Selenium

Selenium is a component of selenoproteins that contributes to the alleviation or reduction of inflammation, DNA damage, and prolonged telomere length and thereby plays a role in fighting age and preventing cardiovascular diseases, neuropsychiatric disorders,  tumors, and skin aging, among others [82,83]. So far, at least 11 selenoproteins have been characterized, and there is evidence that their number is higher.

Glutathione peroxidase (GPx): Four such enzymes are known to be selenium-dependent:  classical cellular glutathione peroxidase (GPx); extracellular GPx, or plasma; phospholipid hydroperoxide GPx; and gastrointestinal GPx. Although each GPx is a distinct selenium-dependent enzyme, all have an antioxidant function by reducing ROS, such as peroxide ions and lipid hydroperoxides, by coupling the reduction reaction with the glutathione oxidation reaction. Selenoprotein from sperm capsule mitochondria, an antioxidant enzyme that protects sperm from developing oxidative damage and which later forms a structural protein required for mature sperm, was considered a distinct selenoprotein but subsequently proved to be a phospholipid hydroperoxide GPx. Thioredoxin-reductase: together with thioredoxin, this enzyme participates in the regeneration of several antioxidant systems,  including vitamin C.

Maintenance of thioredoxin in reduced form by thioredoxin-reductase is important for regulating cell growth and viability [84]. Iodothyronine-deiodinase (thyroid hormone deiodinase): The thyroid gland releases in the blood very small amounts of active thyroid hormone (triiodothyronine = T3) and larger amounts of its inactive form (tetraiodothyronine = thyroxine = T4). Most T3 is synthesized by removing an iodine atom from T4  through a reaction catalyzed by selenium-dependent iodothyronine-deiodinases. There are three known iodothyronine dyskinesias designated I, II, and III, which, by their action on T3, T4, and other metabolites of the thyroid hormone, can activate/inactivate the thyroid hormone, making selenium an essential element in the normal development and growth as well as in the metabolic pathways controlled by thyroid hormone [85]. Seleno-protein P is found in plasma and is associated with endothelial vascular cells at the level of the internal wall of blood vessels.

Although the functions of selenoprotein P have not been fully elucidated, it is assumed to be a transporter protein, an antioxidant capable of protecting endothelial cells from attack by reactive nitrogen species (NRS) called peroxynitrites. Seleno-protein W: this is found in muscles. Although its function is unknown, it is thought to play an important role in muscle metabolism. Selenophosphate synthetase: this is the enzyme that catalyzes the reaction of incorporation of selenocysteine into selenoproteins. This protein catalyzes the synthesis of selenium monophosphate, a selenocysteine precursor that is required to synthesize selenoproteins.

Being an integral part of GPx and thioredoxin reductase, selenium interacts with each nutrient, affecting each cell’s pro-oxidant/antioxidant balance. It is assumed that selenium from GPx is an activator of vitamin E in lipid peroxidation. Studies in laboratory animals have shown that selenium and vitamin E protect each other. It appears that selenium may prevent some of the disorders that occur as a result of vitamin E deficiencies. In addition,  thioredoxin reductase maintains the antioxidant functions of vitamin C, catalyzing its regeneration reactions.

Selenium deficiency can counteract the effect of iodine deficiency. Iodine is essential for thyroid hormone synthesis, but splenocyte deiodinases are also required for T4 to T3  conversion. Selenium supplementation in the elderly diet decreases the concentration of T4, indicating that an increase in deiodinase activity may increase the conversion rate of T4  to T3 [86,87].

4.4. Role of Zn, Cu, and Se in the Aging Prevention

The role of Zn in aging and immunosenescence has recently been reviewed [78]. Zn, which is often deficient in the elderly, rules many functions characterizing the so-called “oxi-inflame-aging”, at least because of the aforementioned functions at the biochemical level [78,88]. A proper plasma level of trace elements, such as Zn or Cu, promotes an optimal function of the immune response [75]. High levels of copper, for example, have been associated with cognitive impairment [89]. In this context, the role of micronutrients is particularly crucial [90].

For example, Se is a fundamental cofactor in many redox functions, which reduces ROS-induced degeneration in the senescent phenotype [91]. Cofactors of major enzymes involved in the clearance of oxidative stressors are surely beneficial in preventing aging-related damage [90]. In the case of Zn, its role in the optimal function of the immune responses appears particularly crucial, as old mice with reduced zinc levels reported an increased proinflammatory cytokines profile, such as MCP1 and IL6 in the serum, also showed increased Th1/Th17/inflammatory cytokines (IFNγ, IL17, TNFα, respectively), and decreased naïve CD4 T-cells in the mesenteric lymph nodes (MLN) [92]. The ability to enforce immunity in the elderly and to delay the immunosenescence mechanism is a leading role of these trace elements, usually in the form of metal cofactors [93–96].

5. Carnitine 

Amino acids are the components of proteins that significantly contribute to aging-related diseases [97]. Perspective natural UV-absorbing compounds for skin protection are mycosporine-like amino acids, which can absorb UV radiation and disperse the absorbed energy without generating reactive oxygen species [98].

However, dietary intake of an excessive amount of a single amino acid can be toxic [97]. The multifunctional anti-inflammatory carnitine and its acetyl derivative l-carnitine are amino acids that play an essential role in fatty acid transport within the mitochondria that convert metabolic pathways into energy. Carnitine is a non-essential amino acid that plays a role in the transport system. It binds the free fatty acids in the cytoplasm to cross the two membranes of the mitochondria to be later oxidized; thus, it is not an enzyme but a transport system.

The main function of carnitine is the transfer of long-chain fatty acids (LCFA) to mitochondria for subsequent β-oxidation. This process provides biological energy, starting from a lipid substrate, not glucose. The advantage is that simultaneous fat loss occurs through the preferential use of lipids. Carnitine is found on the pharmaceutical market and as a nutrition product (vials with oral carnitine) for athletes. As a non-essential amino acid, carnitine is not prohibited by sports ethics; moreover, a diet rich in animal proteins brings significant quantities of carnitine into the body. For this reason, carnitine is a good adjuvant of local anti-cellulite treatment and physical culture. It stimulates the formation of muscle mass by reducing fats.

6. Plant Metabolites

Various plant metabolites derived from polyphenols, triterpenes, and sterols classes demonstrated promising antioxidant and anti-aging effects [99,100]. Plant-derived antioxidants, both by topical and oral applications, may prevent free radicals’ over-production and, therefore, different diseases caused by oxidative stress and redox-derived stressors,  including aging [17,101]. Secondary phytoconstituents include polyphenols (stilbenes,  anthocyanins, epigallocatechin gallate, curcumin, rosmarinic acid, flavonoids, etc.), and play a significant role in limiting aging processes in the body and skin due to the ability of OH-groups to inhibit the influence of free radicals [18,102–104]. After the transdermal application of rosmarinic acid, its inhibitory effects on collagenase, elastase, and antioxidant activities were proved [105]. Blueberry anthocyanins effectively protect against the aging process in the epithelial cells [106]. Quercetin improved the spatial learning and memory impairment of aging mice [107]. A high level of polyphenols such as epigallocatechin gallate, catechin, rosmarinic acid, flavones, etc., evaluated in green tea and some medicinal herbs, is the key to their antioxidant potential [108–110]. Dietary consumption of flavonoid-rich foods and nutraceuticals can improve cognitive function and inhibit senescence [111]. Increasing the consumption of phytosterols may be an important way to reduce cholesterol levels and prevent coronary heart disease, cancer, wrinkles of the skin, etc. [112].

6.1. Polyphenols 

Multiple polyphenols have substantial health-promoting effects as they are powerful antioxidants [113]. Flavonoids are components in many fruits and vegetables containing yellow, red, or blue pigments; they have antioxidant activity, similar to vitamin C, and an anticarcinogenic action [114].

Polyphenols are some of the most potent antioxidants in food. There are over 8000 polyphenolic structures identified in plants and these compounds are present mainly in fruits, vegetables, tea, wine, cocoa, aromatic plants, or coniferous bark [115]. Polyphenols can be in the form of anthocyanins (in red fruits), flavonoids (in citrus fruits),  quercetin (in tea leaves, cocoa, onions, algae, apples), resveratrol, stilbenes (in grapes,  pomegranates), lectins (in legumes), and lignans (in flax seeds) [106].

Chemically, they contain one or more aromatic nuclei, on which several hydroxyl groups are grafted, and four main classes of polyphenols are known: flavonoids (cvercetol,  kaempferol, luteolin, genistein, simple and condensed catechins, proanthocyanidins, the latter being commonly classified in the category of tannins), phenolic acids (chlorogenic acid, rosmarinic acid, ferulic acid), stilbenes (trans-resveratrol), and lignin derivatives (pinoresinol). Plant polyphenols are one of the most important categories of natural active principles with antioxidant effects, being increasingly used in skin antiaging therapy, having remarkable properties in combating the harmful effects of solar radiation and atmospheric pollutants, and preventing and alleviating the symptoms of premature skin aging. Specifically,  polyphenols are recognized for their antioxidant, anti-inflammatory, antibacterial, antiviral,  antitumor, and anti-atherogenic action (against deposition on blood vessels) [116,117]. The main action of antioxidants is to prevent the formation of free radicals, fighting against aging processes. Polyphenols are especially useful for the plants in which they are found. Plants use them to protect themselves from parasites and microbes, from ultraviolet rays,  and to favor the pollination process. Then, once they reach the human body, the polyphenols intervene to protect the cells from oxidative stress, inflammation, and genetic mutations.

Experimental studies have shown that at topical application, polyphenols can combat some clinical and histological changes in the epidermis and dermis induced by exposure to UV radiation and chronological aging, causing the restoration of the keratinocyte ultrastructure, stimulation of collagen synthesis, improvement of vascularization or normalization of hyper-keratinization, being able to function in different phases of aging, as this is a stepwise process. Each phase or clinical form involves a specific treatment. Plant species with a high concentration of polyphenols of cosmetic interest include Vitis vinifera (vines), Punica granatum (Rodia), and Camellia sinensis (tea). The fruits of Vitis vinifera, the grapes, have anti-aging activity at the skin level due to their content of proanthocyanidins and transresveratrol, showing protective effects against oxidative stress induced by UV radiation mainly by supporting the functionality of endogenous antioxidant systems, preventing (photo) macromolecular biological degradation (lipids, proteins, DNA) and inhibition of the activation of cellular signaling pathways MAPK (mitogenic ally activated protein kinase)  and NF-kB (nuclear factor kappa B), involved in photocarcinogenesis.

Pomegranate polyphenols (flavonoids, proanthocyanidins, and, in particular, punicalagintype ellagitannins) exhibit antioxidant, anti-inflammatory, and antiproliferative action, and DNA regeneration capacity, resulting in photoprotection and photo-chemoprevention. Phenolic acids are simple molecules easily absorbed into the human system and offer several anti-aging benefits. In addition to making cells stronger and resistant to degradation,  the anti-aging property of phenolic acids is correlated with antioxidant activity that also prevents abnormal cell growth.

Phenolic acids are also useful in controlling inflammation, stimulating the immune system, limiting the collagen fiber breakdown by various mechanisms, helping to form natural collagen fiber bonds and preventing them from being caused by free radicals, and improving circulation to the blood; all of these together produce significant anti-aging benefits in the body [113]. The antiaging skin effect is achieved by inhibiting morphological changes in the fibroblasts, stimulating the expression of type I procollagen, inhibiting MAPK, and NF-kB activation, inhibiting UVB-mediated cell proliferation, and reducing epidermal hyperplasia induced by UVB radiation and leukocyte infiltration.

A major source of inflammatory reactions and oxidative stress, inhibition of matrix metalloproteinase activity (MMP-1, -2, -3. -7, -9, -11, -12), important in the degradation of extracellular and photo-aging matrix components, and also by inhibition of COX-2  cyclooxygenase and inducible nitric oxide synthase, enzymes involved in the processes of skin inflammation and cell proliferation.

The flavonoid, 4,40 -dimethoxy chalcone (DMC), which occurs naturally in the Ashitaba plant, induces a process called autophagy (a process of cleaning and recycling). DMC has been investigated as an anti-aging compound with cardioprotective effects in mice and can potentially promote longevity among species. For example, when Dasatinib (a leukemia drug) and quercetin (a natural product found in vegetables) are combined, improved health and prolonged life are observed [118–121].

Tannins represent the group of water-soluble phenolic compounds. The tannins in grapes are responsible for the astringent taste and body of the wines. Tannins in grape seeds help lower LDL (low-density lipoproteins) and VLDL (very low-density lipoproteins)  cholesterol and increase HDL (high-density lipoproteins). Tannins reduce the intestinal absorption of cholesterol and improve bile excretion; thus, bile salts bind to cholesterol and tannins, which are eliminated through feces. This mechanism of eliminating cholesterol from the intestinal lumen seems similar to dietary fiber intake.

The astringent action is highlighted on mucous membranes and tissues. The mechanism of action is explained by the coagulation of proteins that have a retracting effect by shrinking the lesion’s surface. A precipitation reaction of the microorganism explains the antiseptic action; it protects the wound from infections. The hemostatic action is defined by the precipitation of red blood cells. The astringent action explains the antidiarrheal step. They are used as an antidote, especially for alkaloid poisoning. In therapeutics, they are used for anti-irritating, anti-inflammatory, bactericidal, hemostatic, mild local anesthetic,  and reducing secretions’ effects [122].

6.1.1. Resveratrol

Resveratrol is a polyphenol of the stilbenoids group detected in high quantities in grapes’ skin, seeds, and red wines. This phytoalexin possesses a very promising antioxidant potential [123–125]. Resveratrol may extend the lifespan of humans by activating the SIRT1  and sirtuins’ molecules. Sirtuins are a class of enzymes that control cellular metabolism by regulating the expression of certain genes. It is known that resveratrol is a sirtuin 1 activator, represented by the SIRT1 gene, improving mitochondrial function and slowing the proliferation of certain cancers. This gene also controls the longevity of several species of animals, including the longevity of humans.

Resveratrol could inhibit apoptosis and morphological modifications stimulated by H2O2 treatment, increase proliferation, and reduce acetylated TP53 [126]. Resveratrol (found in red grape bark, Polygonum cuspidatum, groundnuts, blueberries, and other berries)  is a chemical compound that some plants synthesize to remove bacteria and fungi, as well as to protect against ultraviolet (UV) radiation.

Preclinical studies on resveratrol have shown an increase in longevity in S. cerevisiae by 70% by cultivation on a medium containing 10 mM resveratrol, 20% of C. elegans, 29%  of Drosophila melanogaster by treatment with 100 mM resveratrol. In studies in laboratory mice, resveratrol in doses around 20 mg/kg resulted in a statistically significant decrease in age-related parameters: albuminuria; inflammatory levels; vascular endothelial apoptosis;  decreased aortic elasticity; cataract incidence, etc., being recorded, including data on reducing genetic instability [106].

Resveratrol protects against Alzheimer’s disease by blocking the NF-Kb protein, thus preventing microglia from destroying neurons. There are encouraging studies regarding the therapeutic potential of resveratrol and other neurodegenerative diseases.

Resveratrol has also been beneficial for exercise and physical and mental performance. Resveratrol’s effects, similar to phytoestrogen hormones, are very promising: it is the most powerful calcium fixator in bones (in addition to physical exercise), effectively preventing and combating osteoporosis; it confers major vascular protection, even in men; combats climacteric disorders; helps to regulate the menstrual cycle and cancels the effects of dysmenorrhea; even in excess, it provides protection against breast and cervical cancer and does not induce cancer; protects the nerve cells against the devastating effects of stress,  prolongs their life and prevents their apoptosis; promotes the renal elimination of uric acid, preventing its accumulation and the risk of degeneration in gout or uric lithiasis;  increases the synthesis of endogenous antioxidants, of the substances needed by the body (phytoestrogens are enzyme-inducing substances—hepatic—with a role in detoxifying the body).

In MRC5 human fibroblast cultures, 5 µm resveratrol induced significant protection against oxidative DNA damage, preventing increased nuclear volume, and reduced generation of acetylated forms of histones H3 and H4, and p53 protein. In another study on human fibroblasts, the use of a concentration of 10 µm and 25 µm led to data that supported the delay in the appearance of morphological changes at the cellular level correlated with age [106]. Resveratrol-like polyphenols are supposed to inhibit cellular senescence by activating p53 and AKT genes, sirtuins, or inhibiting others, such as mTOR. They influence different intracellular signaling pathways by which the expression of genes involved in cell growth, proliferation, and cell viability are controlled. Clinical studies on the action of resveratrol in oncology using a commercial form of resveratrol called SRT501 showed a 39%  increase in malignant cell apoptosis in patients with metastatic colorectal cancer [106].

The neuroprotective effects of resveratrol have been described experimentally in laboratory mouse studies. They have also been explained by researchers through the effect of growth resveratrol on the level of cysteine that can protect cells from oxidative stress by controlling the protein precursors of the amylase plate. Resveratrol also acts on manganese superoxide dismutase (MnSOD), a group of enzymes that degrade the generated superoxide molecules' metabolic, therefore having an antioxidant effect [106]. The cardioprotective effect of resveratrol and other polyphenolics such as quercetin or catechins have been observed in in vitro studies showing a reduction in cardiomyocyte apoptosis by lowering caspase-3 levels and other cytokines, including NF-kB2, E selectin,  troponin, or TNF-α [127].

Resveratrol also has an anti-inflammatory effect, leading to decreased cyclo-oxygenase activity, with a key role in synthesizing other cytokines such as IL17. The hypothesis of the antidiabetic use of resveratrol is explained by the activation of SIRT1 and subsequent increase in insulin sensitivity, improvement of microcirculation, and peripheral nerve function [128]. Resveratrol also acts on the cellular mechanisms involved in photo-aging correlated with the action of UV rays, including MAP kinases, nuclear factor NF-kB and matrix metalloproteins. External applications of resveratrol to the SKH-1 hairless mouse model before ultraviolet exposure resulted in a significant reduction in cell proliferation,  mRNA protection, and phosphorylation. However, the pharmacology of resveratrol is marked by several limitations: low water solubility and consequently low bioavailability, and stability, and is easily oxidizable in the presence of light or heat. Even the data contradict that resveratrol would result in the extension of longevity, obtained in research on Drosophila melanogaster and C. elegans and disseminated by some authors [129].

6.1.2. Curcumin 

Curcumin can positively slow down aging by suppressing age-related changes in the inflammatory processes [130]. Research on aging and related traits of curcumin in model organisms has reported that curcumin and its metabolite, tetrahydro-curcumin (THC),  could increase the mean lifespan of at least three investigated model organisms such as the fruit fly Drosophila, mouse, and nematode roundworm.

A significant elevation of lifespan could be seen by decreasing the production of reactive oxygen species by genes (skin-1, sek-1, or-1, mek-1, sir-2.1, unc-43, and age-1) in the nematodes’ models grown on enriched media with curcumin. The extension of the lifespan of Drosophila by curcumin supplementation was related to declined malondialdehyde and lipofuscin levels and increased superoxide dismutase activity (SOD) [131]. Curcumin also reverses endothelial dysfunction and artery stiffness and may be a novel therapy for treating arterial aging in humans [132]. Curcumin is currently used to treat numerous disorders, particularly those that contribute to an inflammatory process. Curcumin and its derivatives have been reported to have a powerful anti-cancer function, particularly on cancer stem cells (CSC) [126].

6.2. Terpenoids 

Due to terpenoids, essential oils showed their valuable anti-aging potential in treating anxiety, dementia, and other neurological disorders via in vitro, in vivo, and clinical studies [111,133]. Essential oils are useful as multi-potent agents due to their composition of several valuable components [134,135]. Aromatherapy with essential oils can improve cognitive performance in patients with Alzheimer’s disease [133,136]. The use of essential oils and essential oil-bearing plants can provide significant benefits to health through cognitive improvements.

A combination of aromatherapy by topical, inhalation, or ingestion mode of application can enhance the positive effect on the human body [133,136]. Molecules of terpenoids are small and can be transferred across nasal mucosa during inhalation, enter into the blood and penetrate through the blood–brain barrier, or cross through the skin after topical application due to fat-soluble properties [133]. Ursolic acid, a pentacyclic triterpenoid in many fruits and herbs used in daily life (apples, prunes, cranberries, elder flower, peppermint, rosemary, holy basil, bilberries, etc.), has hepatoprotective properties to enhance the anti-aging biomarkers [137].

6.3. Other Natural Compounds from Medicinal Plants

Usually, many plant-derived phenolic and polyphenolic substances, which include the commonest flavonoids (isoflavones, lignans, flavones, and so forth), behave as phytoestrogens, namely compound with a hormonal-like function, usually on estrogen receptors. Not all of these compounds act yet by targeting estrogen receptors. Studies on these compounds have demonstrated their efficacy in preventing carcinogenesis with localization to the mammary, prostate, and colon glands and preventing osteoporosis.

Many kinds of vegetables, when eaten raw, have substantial anti-aging effects because they slow down the development of Alzheimer’s disease [138]. Most of them are the representatives of botanical families such as Amaryllideae (onion, garlic), Apiaceae (carrot, parsley, dill), Asparagaceae (asparagus), Brassicaceae(red cabbage, broccoli, radish), Cucurbitaceae (cucumber, pumpkin), Fabaceae (soybean, red bean), Dioscoreaceae (Yam), Amaranthaceae(Chinese Spinach), Asteraceae (Artichoke), etc.

Medicinal plant sources include, amongst others, seaweeds, Allium sativum, Cynara scolymus, Crataegus spp., Ginkgo biloba, Hippophae rhamnoides, Panax ginseng, Schizandra chinensis, Silibum marianum, and Aloe vera, representatives of which are very useful in the prevention of aging-related ailments [6,17,139]. For instance, the common application of the Allium sativum extract and coenzyme Q10 showed a favorable effect on inflammatory parameters and atherosclerosis progression [140]. S-Allylcysteine, an organosulfur molecule from aged garlic, can ameliorate the aging process by regulating mitochondrial functions [141].

Diallyl sulfide, also found in garlic, has also been found to aid the elimination of arsenic from the body proving effective in ameliorating arsenic toxicity [142,143].

Silybum marianum seed oil effectively decreased oxidative damage, and improved mitochondria function in the liver of aging mice [144].

Ginkgo biloba leaf extracts are widely used in the treatment of various degenerative diseases such as cerebrovascular disorders, Alzheimer’s disease, skin aging, etc., due to their ability to prevent mitochondrial dysfunctions and apoptosis [145].

6.4. Alpha-Hydroxy Acids (AHAs)

These are plant- and animal-derived substances used in various skincare products. Alpha-hydroxy acids (AHAs) such as citric acid (CA), glycolic acid (GA), lactic acid (LA),  malic acid (MA), and tartaric acid (TA), are the naturally-occurring organic acids found in many fruits, berries, and herbs [146–149]. They are mostly used to reduce the impact of acne and enhance dry and aging skin. They help remove the top dead epidermal layers and promote the firmness of the deeper layers of the skin [149].

There are seven types of AHAs commonly used in products usable everywhere in the mass production of skincare. These are the following compounds and sources: the already mentioned citric acid (from citrus fruits), glycolic acid (from sugar cane), hydroxy caproic acid (from royal jelly), hydroxy caprylic acid (from animals), lactic acid (from lactose or other carbohydrates), malic acid (from fruits), and tartaric acid (from grapes). Out of all of the AHAs available, glycolic and lactic acids have the most trusted sources and which have been most studied. However, both glycolic and lactic acids can irritate [146].

AHAs are first and foremost used to exfoliate. AHAs have important implications for lightening the complexion, correcting discoloration from scars and age spots, improving the appearance of surface lines and wrinkles, increasing product absorption, preventing acne breakouts, and promoting collagen and blood flow [146]. Another acid particularly used in the skincare market is beta-hydroxy acid (BHA). In contradistinction to AHAs, BHAs are mostly synthesized from one source: salicylic acid (an acne-fighting ingredient) [146]. The studies evidence that their advantages extend far beyond exfoliation. AHAs facilitate the synthesis of glycosaminoglycan and collagen production and enhance the number of elastic fibers.

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