Natural products as antiaging agents

1. Astaxanthin may delay brain aging

Even if you've never heard of astaxanthin, a carotenoid derived from the microalgae Pluvialis haematoccous, you've probably seen it.

This is the compound that gives the red or pink color to salmon, crabs, lobster, shrimp, and flamingos, which eat these algae.

Astaxanthin is emerging as one of the world's most powerful antioxidants, with diverse health benefits ranging from protection against oxidative stress to age-related functional slowing. While astaxanthin is often revered for its antioxidant potential, some recent studies have also recently highlighted its unique anti-aging properties.

What Makes Astaxanthin Such a Powerful Antioxidant?

Antioxidants are essential to your health because they are believed to help control the way you age by fighting free radicals, which are the main cause of age-related cell deterioration.

Free radicals are generated in response to environmental toxins, such as cigarette smoke, chemicals, sunlight, and cosmic radiation, and are even a key byproduct of the consumption and detoxification of pharmaceutical drugs.

Free radicals are also produced as a result of normal metabolic processes in your body, but they can rise to dangerous levels when you have abnormally high inflammation or when you exercise intensely.

A free radical is a highly reactive molecule that is missing one or more electrons--they have at least one unbalanced electron. These "partial molecules" aggressively seek to replace their missing pieces by attacking other molecules. This continuous search by free radicals for missing electrons is largely responsible for the process of biological oxidation.

Lipids in cell membranes are very susceptible to oxidative damage because they are often the first free radical biomolecules to come into contact as a result of "lipid peroxidation", i.e. rancidity. When a cell membrane is oxidized, it becomes fragile and porous. Eventually, the cell disintegrates and dies.

While, by definition, any antioxidant can inhibit the oxidation of another molecule at the cost of sacrificing its own electrons to quench free radicals, without becoming free radicals itself, astaxanthin exerts a unique protective action on cell membranes. Astaxanthin neutralizes free radicals or other oxidants, by accepting or donating electrons, and without being destroyed or becoming a pro-oxidant in the process.

Due to its tropism in the brain, Astaxanthin has recently been studied as a putative neuroprotective molecule capable of delaying or preventing brain aging in different experimental models of brain damage or neurodegenerative diseases. Astaxanthin has been observed to slow brain aging by increasing brain-derived neurotrophic factor (BDNF) levels in the brain, attenuating oxidative damage to lipids, protein, DNA, and protecting mitochondrial functions.

2. Curcumin and Polyphenols in neurological function and antiaging

The deterioration of the nervous system in senescence, together with the appearance of age-related neurodegenerative diseases (such as Alzheimer's or Parkinson's) can affect the motor system and generate cognitive and memory deficits and behavioral alterations in people. Therefore, it is extremely important to explore methods to delay or reverse age-related neuronal deficits, as well as their subsequent behavioral manifestations, and to be able to enhance healthy aging.

In this regard, consumption of diets rich in antioxidants and anti-inflammatory polyphenols, such as those found in turmeric, grapes, blueberries, and other fruits and vegetables, may decrease the risk of developing age-related neurodegenerative diseases.

Research suggests that these polyphenolic compounds may exert their beneficial effects either through their ability to reduce oxidative stress and inflammation or directly by altering signaling involved in neuronal communication. These interventions, in turn, may protect against age-related deficits in cognitive and motor function.

Curcumin

Turmeric rhizome was adopted as a medicinal product by the Committee on Herbal Medicinal Products (HMPC) on November 12, 2009. This plant has been used in a multitude of traditional medicine systems (Chinese and Ayurvedic). In turn, the National Center for Complementary and Integrative Health (NCCIH) of the US Department of Health has studied the effects of curcumin on Alzheimer's disease.

The phytochemical compounds present in its characteristic orange rhizome, curcuminoids, give this plant important medicinal properties.

These medicinal properties of turmeric are attributed to the bioactivity of components produced in the secondary metabolism pathways: phenolic compounds and volatile oils. The phenolic compounds present, specifically polyphenols, are from the curcuminoid group which comprise 2-9% of the plant and are responsible for the yellow-orange color of turmeric.

Research has shown that these curcuminoids are involved in a wide range of processes at the neuronal, cardiovascular and hepatic levels. But the main problem with these secondary metabolites is their low bioavailability: curcumin is not soluble in water at neutral or acidic pH, undergoing rapid glucuronidation that makes it poorly bioavailable and is excreted. It is therefore recommended that for greater bioavailability curcumin be given in liposomal form, as this protects it from the aggressive conditions of the stomach and achieves maximum absorption of the free (active) curcumin, the only curcumin capable of crossing the blood-brain barrier.

Blueberries

Blueberries are rich in polyphenols, which can provide multiple health benefits. According to a study, regular consumption of blueberries can help prevent pathologies associated with metabolic syndrome, including cardiovascular disease and diabetes.

Eating blueberries can help you keep your brain in good condition, even in old age. Blueberries contain flavonoids that boost your memory and improve learning and other cognitive functions. They protect your brain from free radicals that can damage healthy tissue and are often linked to memory loss. Blueberries may also help reduce the risk of Parkinson's or Alzheimer's disease.

3. Mtor: the molecule that builds new cells and destroys those that are useless

The fundamental activity of our body is to build new cells and destroy useless ones. There is a molecule called mTOR that controls this delicate balance.

Proteins are fascinating molecules. Not only are they building materials for making muscles, bones, blood, and entire organs, but they also act as messengers, catalysts, or inhibitors of chemical reactions in your body, as well as antibodies to defend you from attack. If you take all the water out of your body, 40% of what's left is protein. We are proteins.

Your DNA is a set of chemical "templates" for making the thousands of different proteins you need to function.

This process of combining those amino acids into useful proteins is called protein synthesis, and it is the basis of life. Your cells are not immortal, they are in a continuous process of regeneration.

Until recently it was thought that protein synthesis, and therefore the creation of new cells, occurred spontaneously when there was enough energy and amino acids available from food. However, only 20 years ago it was found that this process was strictly regulated by a protein called mTOR.

When mTOR is not well regulated, there is premature aging, diabetes, obesity, cardiovascular disease, and cancer. If they work properly, it can give you iron health and many more years of life. That's why it matters to you.

What is mTOR for?

The signaling pathway is activated when cells detect one of the following:

• Amino acids in the blood (when you eat protein).
• Growth factors, such as Insulin, which is triggered when you eat carbohydrates.
• Energy (either glucose or fat)
• DNA damage

When mTOR is activated, along with the other molecules it triggers these processes:

• Inhibits autophagy, or recycling of damaged parts of the cell.
• Starts protein synthesis
• DNA and RNA synthesis
• Inhibits apoptosis, or programmed death of damaged cells
• Glucose metabolism

So mTOR is the key to the most important processes in your body. Is it good for you if it is active or inactive? Both! In fact, having too much mTOR is just as bad as having too little.

It turns out that mTOR is also the key to building muscle mass, which is associated with great health benefits. Protein consumption and intense physical exercise produce a combination of cell damage and amino acids in the blood, which kick-starts the muscle-building process.

The problem is therefore when the mTOR system is too activated. If there is no autophagy or programmed cell death, all the conditions are in place for unrestrained cell growth, what does that look like? In effect, a tumor. Excessive activation of mTOR is associated with the development of breast cancer, prostate cancer, lung cancer, melanoma, bladder cancer, brain tumors, and kidney carcinomas. By the same process, neurodegenerative diseases such as Alzheimer's disease are also prevented.

4. Anti-aging formula with resveratrol

Senescent cells have been rejuvenated thanks to a molecule already known for its effects on longevity: resveratrol.

Resveratrol is a polyphenol present in some fruits such as grapes and blackberries, but also in the roots of Poligonum cuspidatum from Japan (Hu Zhang), a plant used in traditional Chinese medicine considered to be the best natural source of resveratrol. Resveratrol is found in cis and trans configuration, but the latter is the most active form in humans.

A few hours of treatment were enough to transform aging cells into young cells that divide again. To achieve this, the researchers relied on the properties of resveratrol. Earlier studies had shown that this natural chemical compound could restore the function of a certain class of proteins that declines with age: the splicing factors.

These are at the origin of an important step in the manufacture of proteins, the splicing of RNA (ribonucleic acid) strands, which consists of preparing copies of genetic information to be sent out of the nucleus and translated into proteins. When the splicing factors diminish or deteriorate, it is the whole mechanism for making all the proteins that suffers. And it is a very frequent condition found in the cells of most organs of the elderly.

Therefore, by rehabilitating the splicing factors of aging cells, the researchers have not made a mistake: it is the whole cell that is revived. It recovers the resources necessary to ensure a large number of functions that it had abandoned, such as cell division or adaptation to its environment. And this effect is preserved over time!

This discovery, which confirms the interest of resveratrol in combating aging, is a major step towards the development of a universally accessible treatment to prevent and treat degenerative diseases associated with aging.

Moreover, a recent study from University College London has uncovered an interesting explanation for its potential as an anti-aging substance. The study demonstrated that resveratrol can mimic the hormone estrogen in the human body to activate anti-aging proteins called sirtuins, which can help prevent age-related health problems.

It’s main objective was to explore the dietary compounds that are dietary-activated, which includes resveratrol. Sirtuins have become a target of interest for researches, as they are proteins produced by the body which have effects on metabolism.

Sirtuins also protect about conditions such as cancer, obesity, type 2 diabetes, as well as neurodegenerative diseases.

Interest in sirtuins began in 1999, when it was reported that activation of the proteins can extend yeast shelf life by up to 70%.

5. Spermidine: the molecule that gives you five years of life

Spermidine, a naturally occurring polyamine molecule, known for its life-prolonging effect in cell cultures and animals, also has an anti-aging effect in humans. The amount of spermidine produced by our body decreases as we age, especially if we do not follow a proper diet.

Spermidine is a polyamine whose structure consists of an aliphatic chain with three amino groups, two of them primary - one at each end - and one secondary. It was first isolated from human semen, hence its name.

Spermidine plays a vital role in cell survival. When present in a cell at moderate levels, it can help stabilize the structure of DNA and histones (proteins that support chromosome structure), maintaining their transcription activity; however, a high level of polyamines causes apoptosis or cell death due to oxidative stress generated by the accumulation of hydrogen peroxide (a free radical).

The substance, which occurs naturally in living organisms, is especially present in humans in sperm, intestinal bacteria and some cells. Some foods rich in this molecule are cabbage, peas, cereals, apples, lettuce, mushrooms, nuts, potatoes or cured cheese.

After about 40 years of age, the human body reduces its natural production, so it is necessary to reinforce its presence in the diet.

The recommendations are the same as always: eat lots of vegetables, fruit, nuts and whole-grain foods, which contain high doses of the molecule. The anti-aging effect of spermidine is mainly due to its ability to stimulate autophagy, a self-cleaning process in cells whereby their defective or no longer needed components are broken down and recycled.

At the molecular level, the main mechanism is autophagy, but there appear to be other mechanisms such as reduction of inflammation, lipid metabolism, as well as regulation of cell growth, proliferation and death.

A study confirms that spermidine, as a natural promoter of autophagy, can compensate for age-related lack of cellular "pruning" by inducing mitochondrial cell death. The results could point to an intriguing method for slowing or even reversing cognitive decline with age. Mitochondria are a key element in cognitive function, as their dysfunction has been linked to age-related memory impairment. Mitochondria play an important role in cellular respiration, a process that is vital for growing healthy cells throughout the body and, in this case, the brain.

Throughout life, mitochondrial quality is controlled by autophagy, giving way to this abundance of healthy breathing cells; however, the machinery that controls autophagy declines as we age, leading to a lack of quality control in the brain. Spermidine, as we have said, could slow down this process.