Researchers have been investigating dietary behaviors such as what we eat, when we eat, and how much we consume for many years to figure out if they can aid in preventing age-related conditions like heart disease, diabetes, and dementia. They are also curious to understand how various dietary habits may have an effect on the wellbeing of our musculoskeletal system, which includes the body’s muscles, bones, and ligaments.
Researchers are very interested in calorie restriction, which involves lessening the daily amount of calories consumed when compared to normal levels, while making sure that essential nutrients are not being deprived of. Calorie restriction can be achieved by not consuming food for a certain period of time (known as “intermittent fasting”) or by consuming fewer calories at certain meals. Research in both animals and humans has demonstrated that reducing calories can lead to betterment in numerous health conditions. For numerous animal species, fasting can increase their lifespan; however, there is no proof that this occurs in humans.
Researchers are trying to figure out what it is about cutting back on calories that might enable animals and humans to remain in good health as they grow older. In the future, this study could result in the production of calorie restriction imitators – medications that imitate the effects of calorie restriction to reduce the speed of aging.
What’s the Science Behind Calorie Restriction Mimetics?
Scientists are studying the possibility that reducing the intake of calories can help people live longer by bringing about modifications in one or more biological processes linked to healthy aging. Biological pathways are akin to a production line inside a factory, as they involve a sequence of chemical reactions that take place inside a body’s cells. It’s like a set of directions with stages that must be completed to finish a task. An illustration of this would be something like the formation of a fresh cell due to the activity of a biological pathway, damage or mending of a damaged cell, transmission of a signal along a nerve, secretion of a hormone, or the activation of a gene which sets off another pathway.
Biological pathways that work smoothly promote good health. People who do not take part in activities that promote health could be at risk for developing illnesses and premature aging. The objective of studying calorie restriction mimetics is to identify possible treatments that target the same pathways that are influenced by calorie restriction, with the intention of discovering a method to increase the amount of time humans can live in optimal health.
Key Biological Pathways in Calorie Restriction Mimetics Research
Researchers interested in calorie restriction mimetics focus mainly on four biological pathways:
- Insulin signaling pathway. When you eat, your body converts food into glucose, which is used for energy. Glucose in the bloodstream triggers the release of insulin, a hormone. Insulin signaling determines whether the glucose is used immediately or stored, as well as where it is stored. Impaired signaling along this pathway can lead to mismanagement of glucose and aging-related diseases like diabetes and heart disease.
- Mammalian target of rapamycin (mTOR) pathway. The mTOR pathway senses when nutrients are available. When it detects enough nutrients, it triggers cell growth. When it detects insufficient nutrients (which occurs with calorie restriction), the mTOR pathway triggers the cell’s defenses against stress. This enhances the cell’s ability to repair itself and to resist toxins and other challenges.
- Sirtuin-1 (SIRT1) pathway. Sirtuins are a group of enzymes involved in metabolic regulation and cellular health. They can increase cellular production of mitochondria, the cell’s powerhouses. SIRT1 is the most studied of the sirtuin group, and signaling along the SIRT1 pathway promotes the ability of cells to resist stress and to survive.
- AMPK pathway. AMPK is an enzyme that contributes to cell stability by triggering reactions that promote the efficient management of energy.
Reducing caloric intake leads to a decrease in the activity of both the insulin signaling and mTOR pathways, while the activity of the SIRT1 and AMPK pathways increases. Scientists are searching for substances that have similar effects to either decrease or increase activity.
Which Compounds Most Interest Mimetics Researchers?
Researchers are presently investigating a variety of medications and experimental compounds to see if they can reproduce the effects of calorie restriction, using the information of fundamental biological pathways that has been acquired. The objects of study include drugs; compounds present in food products; plant-derived extracts; and substances created by the body such as hormones, peptides, and amino acids. Three of the most studied compounds are:
- Resveratrol
- Rapamycin
- Metformin
A compound that is present in nature, Resveratrol is located in red wine, grapes, dark chocolate, blueberries, raspberries, and various types of nuts. It activates the SIRT1 and other sirtuin pathways. Studies performed on animals using resveratrol have revealed properties that are antioxidant, anti-inflammatory, and anti-tumor. However, the evidence from human studies is weak. As an example, the NIA-funded Aging in the Chianti Region study monitored the diets of 783 healthy individuals over a nine year duration to determine the amount of resveratrol they consumed. The research concluded that there is no link between the use of resveratrol and one’s health or life span.
Further investigations are necessary to see if particular doses or preparations could help people age healthily and which groups would profit from it. Research is currently in progress to see if artificial forms of resveratrol can be useful in slowing down the aging process.
A material called rapamycin is created by bacteria that live in the soil. This compound reduces signaling along the mTOR pathway. Studies have demonstrated that Rapamycin can increase the life expectancy of mice and is beneficial in other ways. A current investigation revealed that providing elderly rats with rapamycin as they aged lessened age-related memory deterioration and avoided age-related declines in the circulation of blood to the brain.
Rapamycin is prescribed for those who have undergone an organ transplant to enable their bodies to accept the transplanted organ. This medication is also utilized to treat individuals with particular types of cancer. Researchers are investigating if lower doses of medication can be taken to imitate the effects of calorie restriction, despite the potential for serious side effects such as insulin resistance, gastrointestinal issues, and infections that can occur from taking the higher doses in certain cases.
Metformin modulates several biological pathways to modify energy production, inflammation, cell vitality, and other factors. This drug, which is regularly employed to manage type 2 diabetes, has been discovered to also guard against other illnesses related to age, like heart disease and cancer. Scientists are looking to acquire a more thorough comprehension of how metformin operates and how its influence may differ dependent on an individual’s gender, age, and other traits. They also want to figure out the amounts of the treatments that could be the most beneficial in reducing the effects of aging.
Researchers are currently looking into the potential anti-aging properties of a variety of different compounds, such as 17-alpha-estradiol, which is a form of estrogen; nordihydroguaiaretic acid (NDGA), which is an antioxidant found in creosote bush leaves; protandim, a mixture of plant extracts like green tea and curcumin; acarbose, which is a drug used to manage type 2 diabetes; nicotinamide adenine dinucleotide (NAD), a form of vitamin B3; and fish oil.
It is essential to keep in mind that no scientific evidence exists to demonstrate that any of these substances can increase the duration of life or health in humans. They should not be taken without consulting a doctor.
What Are the Benefits of Caloric Restriction Mimetics for Health & Longevity?
The need for treatments to take on problems caused by aging and age-related illnesses is more pressing than ever. The aging population is ever-growing and the number of non-communicable diseases is on the rise, so there is a need for plans to address these issues. Cognitive Remediation (CR) and Cognitive Remediation Therapy (CRM) are presently the focus of much attention.
Currently, the only way to extend an individual’s maximum life span is through CR. CRMs may be used in place of actual customer relations, making it more convenient.
- CRMs increase the mean and maximum lifespan in the healthy state.
- CRMs reduce the risks of metabolic disorders (anti-diabetic and liver protection).
- CRMs alleviate symptoms of neurological and neuropsychiatric conditions.
- CRMs have anti-cancer properties.
- CRMs boost immunity and fight inflammation.
Supplements, Dietary and Non-Dietary Strategies as Caloric Restriction Mimetics
Researchers are conducting trials with a range of medicines and substances to find out if they have similar outcomes to calorie limitation, based on the current knowledge of related pathways. The use of pharmaceuticals, compounds derived from food, extracts from plants, and molecules produced in the body such as hormones, peptides, and amino acids are all being investigated as potential supplements. Apart from that, both dietary and non-dietary measures are being looked into as potential risk management strategies.
The Following Are the Top and Most-Studied CRM Supplements:
Curcumin, ginkgo biloba, and green tea
Animal studies have indicated that curcumin and polyphenols from tea can extend longevity. A key element of green tea is epigallocatechin gallate (EGCG). EGCG can boost the fat metabolism process, turn on a “fat-burning” capacity, and be taken as a supplement to support weight loss.
When the results of a study examining the impact of ginkgo biloba on male rat cognitive behavior were compared to a control group, it was surprising to find that the average life span of the male rats was longer (26.4 months compared to 31.0 months).
The National Institute of Aging (NIA) Aging Intervention Studying program is now carrying out experiments on rats to look into the potential benefits of adding substances like curcumin, caffeic acid esters derived from coffee, and medium-chain triglycerides to their diets.
Resveratrol and pterostilbene
It has been noticed that plant compounds that are produced because of stress can be beneficial when used as CRMs (chemical reference materials). Resveratrol is the most widely known of these chemicals, and it can be found in grape skin as well as small amounts in a variety of plant species.
Resveratrol has been demonstrated to stimulate SIRT1, simulating the effects of caloric restriction, and has been proven to extend the life span of many types of animals. SIRT1 has the ability to decrease the pro-inflammatory activity of NF-kB, so resveratrol possesses anti-inflammatory characteristics. In studies done on healthy human participants, administering a large dose of resveratrol resulted in a decrease in the insulin-like growth factor levels, which is connected to Caloric Restriction (CR).
Pterostilbene, a variation of resveratrol that is present in blueberries, has been found to reduce inflammation in cell cultures in a comparable fashion to CR. This is because NF-kB activation and COX-2 activity, both of which lead to inflammation, are decreased.
Fisetin, quercetin, and theaflavins
Examples of plant-derived antioxidants that can protect cells from the harm caused by free radicals created during the metabolic process are fisetin, quercetin, and theaflavins. It has been noted that both fisetin and quercetin have the ability to increase SIRT1, which is an essential molecule associated with caloric restriction.
Fisetin has been shown to stop the unwanted results of mTOR signaling, NF-kB activation, and COX-2 gene expression in laboratory experiments, similar to what Caloric Restriction (CR) does. Additionally, it activates antioxidant and detoxifying gene pathways. It has been shown that Fisetin can increase the lifespan of yeast and fly organisms.
In addition to coming from grape seeds, proanthocyanidins have been shown to reduce the production of inflammatory cytokines, as well as the expression of the cancer-promoting vascular endothelial growth factor (VEGF). Therefore, it has been suggested that it can prevent tumor growth.
The theaflavins are the constituents created during the fermentation of black tea leaves. Theaflavins have been found to increase the longevity of invertebrate species and inhibit the NF-kB inflammatory pathway in mice.
Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN)
Two other compounds that can be found in nature and potentially act as a CRM are nicotinamide riboside and nicotinamide mononucleotide. These molecules are the origin of nicotinamide adenine dinucleotide (NAD+), a compound within cells that functions as a coenzyme and is necessary for many biological processes.
NAD+ is a must-have energy source for the sirtuins to be switched on, and these proteins are responsible for regulating cellular metabolism and DNA repair.
As people get older, their NAD+ levels decrease, leading to a decrease in sirtuin activity. This could potentially lead to issues with the nucleus and mitochondria of cells, as well as a range of illnesses associated with ageing.
Without changing eating habits or exercising, NR and NMN can both raise NAD+ concentrations and SIRT1 activation like calorie restriction and exercise do, and could possibly stop or fix age-related mitochondrial and metabolic issues. Research has demonstrated that giving NR to mice on a high-fat diet increases NAD+ levels and SIRT1 activity, resulting in positive metabolic effects, including decreased weight gain, improved exercise performance, and decreased fat in the liver. NMN has the potential to increase telomere length, making it a very exciting prospect for slowing down the aging process.
Finally, NMN may be the superior option since NR cannot endure in the bloodstream, while NMN can be ingested orally and is accessible.
Cinnamon and metformin
The glucoregulatory agent metformin can be credited with a lot of the gene expression changes observed in mice when they are on long-term caloric restriction. Metformin can decrease the production of chaperones, a set of proteins that have the ability to prevent cell death and stimulate the growth of cancer cells.
Studies have revealed that metformin can increase the average life span of the nematode C. elegans. The potential effects of metformin similar to those of CR could be caused by the way it affects insulin or IGF-1 signaling. It is possible that this technique is the cause for why utilizing Cinnamomum cassia (cinnamon bark) as a glucoregulatory intervention also has the power to prolong the lifetime of C. elegans.
Hesperidin
Citrus fruits, particularly their rinds, contain hesperidin and related flavonoids, which can also be located in various plants. After being eaten, hesperidin is changed into hesperetin and other substances created as a result of digestion. These materials have strong antioxidant qualities and can reduce the levels of lipids, decrease inflammation, and help with diabetes.
It appears that hesperidin’s beneficial impacts on blood sugar and lipid levels could be linked to the AMPK pathway being activated, which is responsible for controlling glucose metabolism and the storing of fat. Furthermore, hesperidin could be beneficial in warding off and curing a range of illnesses connected to growing old.
Conclusion
In conclusion, CRMs have been proven to safeguard against cellular damage, reduce or even reverse the effects of aging, and are likely to extend lifespan.
Further research is necessary to decide the complete impact of these substances, however, it is undeniable that they are leading the way to a period that boosts the current methods of combating age-related illnesses and enhancing general health.
If you are looking to have a healthier body and take advantage of the advantages of reduced calorie intake without having to adhere to stringent dietary restrictions, Calorie Restriction Mimetics may be the solution you have been seeking.