MELATONIN

It is a hormone that is found naturally in our body and is the most important component of the body’s antioxidant system

MITOCHONDRIAL THEORY OF AGING

Aging OCCURS at every level of biological organization. The physiological Capacities of organisms decay Increase During maturation and linearly with age Then.

This process leads to a decrease in resistance and an Increase in cell fragility That, over time, Manifests itself as age-associated diseases. The slow and progressive accumulation of oxygen and nitrogen free radicals (ROS / RNS) That are naturally produced throughout Life is now thought to be one of the main causes of aging. Free radicals, generated in mitochondria Both Those, as well as derived from the cytosol Those, inexorably damage cells, slowly decreasing mitochondrial function. This causes the electron transport chain (ETC) and oxidative phosphorylation to Become inefficient, decreasing the production of ATP. THEREFORE, more vulnerable to mitochondria by ROS Become attack / RNS, further decreasing Their efficiency.THUS, a vicious circle is closed ends in apoptosis or Which programmed cell death.

 

In the vast majority of degenerative pathologies associated With aging, the production of reactive species is Associated With Increased the perpetuation of a chronic inflammatory process. In contrast, ionizing radiation-such as ultraviolet radiation (UVR) -is a clear example of a ROS inducer is responsible for oxidative damage and immune Which damage of peripheral tissues: such as skin. THUS, exposing ‘nude’ to UVR rats produces an Increase in ROS and causes the Langerhans cells in the epidermis to disappear. In skin, This Has Been Correlated With some erythrocytic and epidermal parameters used to measure oxidative stress, especially glutathione disulfide (GSSG), glutathione peroxidase (GPx) and glutathione reductase (GRD), and catalase (CAT).THEREFORE, the aging process Involves Increased ROS production and a progressive loss of Langerhans cells.

Recent data Indicate That, in Addition to ROS, nitric oxide (NO), a component of nitrogen free radicals, Significantly Affects respiration, and is a direct cause of mitochondrial failure. NO and oxygen compete for the same binding site on complex IV of the ETC. As the concentration of NO Increases inside mitochondria, complexes I, II, and III are inhibited, Which severely damages the ETC, Increase Increasing the production of ROS / RNS and RESULTING in the release of cytochrome c into the cytosol in order to initiate the Processes of apoptosis.In Addition, peroxynitrites FORMED by the reaction of superoxide anions With NO, irreversibly inhibit mitochondrial enzymes aconitase Several Such as, reduced nicotinamide adenine dinucleotide (NADH), succinate dehydrogenase, and superoxide dismutase (SOD). If This mitochondrial damage is not repaired Simultaneously,

Some of the No that is derived from mitochondria Reaches Several different NOS isoenzymes, especially nNOS, eNOS, iNOS and, with the Latter producing the massive quantities of NO responsible for MOST of the nitrosative Caused damage in many inflammatory Processes, Including aging itself. Processes in Addition, we now know That Present another iNOS isoform, mitochondrial (i-mtNOS) is found in organelle and this Increases degenerative-inflammatory. i-mtNOS is Very Important Because it can produce, in situ, a lot of the No that mitochondrial respiration Affects negatively.

MELATONIN

Melatonin was first discovered as a product of the pineal gland, we now know, it is produced That , Although the body Throughout. Extrapineal melatonin production sites include the retina, thymus, intestine, liver, brain, skeletal and cardiac muscle, immune system cells, ovaries, testicles, and skin, Among Others. The role of the pineal gland produces melatonin is to cyclically So THAT this hormone can generate a circadian rhythm with a nocturnal peak; Also it synchronises other endocrine and non-endocrine rhythms, sleep-: such as the wake rhythm, antioxidant activity, and the organism’s innate immune system response. Melatonin production Decreases with age, and after the age of 40 years, This Becomes significant decrease.This hormone is Also has non-hormonal functions, Including playing antioxidant, anti-inflammatory, and free radical scavenging role. Melatonin is the Most Important component in the body’s antioxidant system and cellular redox homeostasis Maintains. It has a high capacity to purify hydroxyl radicals and peroxynitrites, as well as superoxide anions, hydrogen peroxide, and NO, THUS Protecting cells from the attack of free radicals These.

Infografía melatonina

Melatonin’s antioxidant activity is threefold: (1) it is a very lipophilic molecule and so penetrates all the intracellular structures and Protects them from oxidative attack; (2) it purifies free radicals and Increases glutathione (GSH), THUS Maintaining the redox balance of cells; and (3) through a genomic effect, it Increases the expression (and activity) of peroxidase and glutathione reductase. This antioxidant activity May be the basis of melatonin’s role in regulating the cell cycle, inhibition of apoptosis Including. Aside from other well-documented STI and experimentally-researched antioxidant and anti-inflammatory activities, melatonin’s ability to inhibit dopamine oxidation Makes it a more potent antioxidant than selegiline and vitamins E and C. In Addition,it can reverse the mitochondrial complex I oxidation induced by MPTP as potent neurotoxins in parkinsonian Such mice, helping the recovery of mitochondrial activity and normal locomotor energy. In a line like, the multi-organ failure Prevents melatonin in rats or mice induced by administration of bacterial lipopolysaccharides, by reducing the expression and activity of iNOS and excessive NO production. Above all, you reduce the expression and activity of melatonin i-mtNOS, Significantly reducing the mitochondrial levels of NO, normalising ETC activity and ATP production. These examples of melatonin’s antioxidant and anti-inflammatory efficacy are the basis of Its clinical utility.

 

 

Melatonin Also Protects against oxidative damage induced by a wide variety of agents and situations produces free radicals Which: such as the carcinogen safrole, Cyanide, the depletion of glutathione, and ionizing radiation. Melatonin is very effective in Protecting DNA, RNA, lipids membrane, and cytosolic proteins against oxidative damage, THUS increase increasing membrane fluidity Increase. Likewise, it scavenges peroxyl radicals generated the lipid peroxidation by different agents During very, treats Including paraquat, bacterial lipopolysaccharides, and MPTP, Among Others. The generation of safrole-induced free radicals, DNA damage and severely Which is carcinogenic, is almost completely blocked by melatonin at doses 100 times lower than safrole. Likewise, melatonin is 100,000 times more effective than vitamins E and C in Protecting the mitochondria from damage induced by hydroperoxides. In Addition, the DNA damage produced by free radicals from other sources, Such as ionizing radiation, is reduced if melatonin is administered beforehand.

Also cytosolic proteins are protected against free radicals by melatonin; in experimental Situations of glutathione depletion (by Administering buthionine sulfoximine, BSO), the appearance of melatonin in newborn rats Prevents cataracts. The chronic administration of melatonin to mice With an accelerated aging profile (SAMP8) preventer the deterioration of mitochondrial function associated With aging, Because it counteracted the oxidative and nitrosative stress and the inflammatory reactions That cause aging, THUS ‘Rescuing’ These senescent mice.

SKIN

Because skin acts as a barrier Between the internal and external environment, it is key in the maintenance of homeostasis. It is in continuous communication With the immune, neural, and endocrine systems and THEREFORE, it shares Numerous Mediators With the Central nervous and endocrine systems. The skin of mammals contains all the molecular and biochemical machinery required to synthesise melatonin from tryptophan. The melatonin produced by skin is metabolised, giving rise to different catabolites: such as N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK). In turn, the formation of UVB Stimulates N1-acetyl-5-methoxykynuramine (AMK) from AFMK. These metabolites are more powerful antioxidants than melatonin itself. In the skin, One of melatonin’s Most Important roles is to counteract the daily oxidative damage induced by UVR and other environmental pollutants. Melatonin acts as an antiapoptotic agent, increase increasing the viability of cells irradiated With UVR and suppressing the formation of ROS. Inhibits lipid peroxidation Also it and NO formation, you reduce the production of polyamines, and Stimulates antioxidant enzymes, as Already Discussed above. Melatonin stabilises Increasing mitochondria by the activity of mitochondrial respiratory complexes and efficiency. All of this Reflects the extraordinary properties of melatonin and Its potential role in skin care. you reduce the production of polyamines, and Stimulates antioxidant enzymes, as Already Discussed above. Melatonin stabilises Increasing mitochondria by the activity of mitochondrial respiratory complexes and efficiency. All of this Reflects the extraordinary properties of melatonin and Its potential role in skin care. you reduce the production of polyamines, and Stimulates antioxidant enzymes, as Already Discussed above. Melatonin stabilises Increasing mitochondria by the activity of mitochondrial respiratory complexes and efficiency. All of this Reflects the extraordinary properties of melatonin and Its potential role in skin care.

It has recently shown Been melatonin That Regulates the expression of apoptosis-related genes in keratinocytes irradiated With UVR, RESULTING in an Increase in the survival of Those cells. The damage produced by ionizing radiation is Caused by Both direct and indirect Mechanisms. The direct effects are the result of the disruption of intracellular molecules, while the indirect effects (accounting for approximately 70% of the damage) are water molecules give rise Because to the formation of free radicals Such as hydroxyl.

RESULTS

It has been shown that melatonin protects cells against the toxic effects of ionising radiation. All of melatonin’s activity in the skin may be the result of its metabolites because UVR stimulates melatonin metabolism, generating AFMK and AMK. Therefore, melatonin can protect the skin’s integrity, helping to maintain the functions of the epidermal barrier, and its antioxidant effects could help to protect keratinocytes and fibroblasts from the damage caused by UVB radiation. Melatonin prevents the erythema and skin damage induced by radiation, as well as having antimutagenic, anticarcinogenic, and oncostatic effects on the skin. Another example of melatonin’s protective effect is a reduction in the damage caused to skin by X-rays. In this sense, the administration of melatonin in combination with radiotherapy is very effective during the treatment of human cancers. Also of note is that pinealectomy in rats is associated with a reduction in skin thickness, producing atrophy of the epidermis, dermis, and hair follicles, while the administration of melatonin reverses these effects. Furthermore, melatonin reduces cutaneous vascular permeability and stimulates angiogenesis, indicating that regular application of melatonin could reduce the development of ulcers and accelerate their healing. Melatonin also inhibits the transcription of α-estrogenic receptor and immunoreactive protein genes in the skin, causing desensitisation of the skin to estrogenic stimuli. All these data indicate that melatonin is an important regulator of the various structures and functions of the skin.

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