Bioidentical Hormone Therapy during Menopause and Anti-Aging

 

Let’s begin by attempting to specify what “aging” exactly is. Cellular aging is seen as the gradual weakening to physical, physiological, and emotional stress. As it continues, cellular functions slowly lose more function, until cellular death occurs.

 

Two types of cellular aging can be observed:

 

-Replicative aging: The limited amount of splitting that a single cell can manage to do

 

-Chronological aging: Calculated by considering the average and maximum amount of time as cell can survive, measured in units of time.

 

Even to this day, be it replicative or chronological, the aging mechanism of the cell has not been fully defined. Research that involves different genetical models has led to the discovery of approximately 20 genes that may help elongate the life span.

 

The cell can respond to DNA damage in the following two ways:

-Apoptosis: Physiological, healthy death. The cell gradually turns smaller, and is able to shred itself   to pieces that other cells can consume and utilize. It supports the cellular system as a whole, as the compromised cells are shredded on their own, and the cells that are not affected can still benefit from it

-Cellular aging: The physiology breaks in an irreversible way through necrosis.

 

“Aging” is a process where the cell cycle gradually and permanently stops.

 

-Our genetic developmental potential

-The cancer genetics named Oncogene

-Oxidative stress

-DNA damages

 

 

“Aging” can also be defined as the decrease in functionality with time.

In every living day, the DNA’s wholeness and stability is threatened by external factors such as physical, chemical or biologic agents, and internal factors such as replication errors, spontaneous hydrolytic reactions and endogenic processes including reactive oxygen types. Such issues snowball into effects such as the stem cell pool getting fractured and intercellular communication getting broken.

 

 

Molecular members of senescence:

 

-Telomeres

-Sirtuins

-Mtor

-Epigenetics

-Mitochondrial dysfunction

 

Let us identify each of these members:

 

Telomeres:

 

As the telomere shortens, we gradually lose more and more of the base pairs within the DNA. They can be compared to the plastic tips of a shoelace. The chemical change within the DNA leads to expressive differences, and the change within the mechanism may lead to the basis of a lot of sicknesses.

 

Telomeres are worn down further every time the cell splits. Telomere length is connected with a lot of sicknesses tied to one’s age.

 

Estrogen can assist in the protection of telomeres in certain mechanisms. Within a study that focused on the telomere length within postmenopausal women going through long term hormone therapy (HT), between 130 women that very between the ages of 55 and 69, the sample group was broken into two groups. The first group were consistently given estrogen and progesterone for about 5 years, while the second half did not have any sort of hormone replacement in their life.

 

Hormone treatment’s approximate length is about 8.4 +/- 2.3 years, and the group that took the treatment was more consistent in their vitamin usage and exercise compared to the group that did not use the hormone treatment. At the conclusion of the study, it was found that the telomere length of the hormone treatment group was much bigger than the other group. Hence, it is proved that hormone treatment may help women in a postmenopausal stage to help upkeep their telomere health.

 

The three scientists that were seen worthy of the 2009 Nobel Prize for physiology, namely Elizabeth Blackburn, Carol Greider and Jack Szostak, had research how to specifically protect the chromosome by copying them. These nominees proposed that the telomeres and the telomerases that create them are the key to the problem at hand.

 

In a study made in 2014, women with the longest leukocyte telomere length entered menopause 3 years later than women with the shortest leukocyte telomere length. No correlation between the telomere length and the menopausal age within women who had their ovaries surgically removed for a gynecological problem. Looking at these results, leukocyte telomere length may be a consistent way to gauge the menopause age.

 

As one continues to age, their telomeres shorten, which is caused by chronic stress, alongside different chronic sicknesses. According to the study, women who suffered with chronic inflammation and/or chronic stress between the ages of 20 to 50 are observed to have smaller telomere lengths. One’s fertility rate was tied to the telomere length as well. It’s important to emphasize that insulin resistance is usually the head of the many chronic inflammatory illnesses as well.

 

Still, it’s easy to see that the telomere length on women tends to be much longer than men, which is why the life expectancy for women is generally longer than men.

It seems that women who are married and actively live with a partner seem to have longer telomere lengths than men, as well.

 

Epigenetic

 

From the embryotic stages to the end of one’s life, different environmental factors tend to lead to changes within the genetic expression of an individual. This new term is called epigenetic, which approximately means “genetic over genes” in the literal sense.

 

Through epigenetic mechanisms, a parent can transfer an environmental effect to their child, and even to further descendants. The most known epigenetic mechanism is called DNA methylation, which is the process in which chemical methyl groups being added to the DNA. DNA methylation leads to the genes getting pressured and may end up with the affected gene changed in certain ways, and histone acetylation helps to reactivate the gene.

 

Outer effects such as cigarette and alcohol consumption, lack of physical activity, obesity, psychological or physical stress, trauma, contagious illnesses, environmental pollution and different cases that gets in the way of a healthy sleep schedule, alongside many other examples, are factors that may change our epigenomes.

Epigenetic clocks are used to gauge the DNA methylation, which gives a clearer picture of the biological age of an individual.

 

According to the Horvath Clock theory proposed in 2010, biological aging is directly related to the methylation of the DNA. Hence, slowing down DNA methylation may lead to slowing down the aging process of the body. Methylation, being a part of the well-known Phase 2 Detoxification, being present for extreme amounts can also lead to being a serious problem in the future.

 

It was deduced that women with postmenopausal obesity have a stronger DNA methylation rate in a study in 2012.

 

Consuming folic acids, staying away from cigarettes, and certain forms of fasting and hormone replacement therapy are seen to lower DNA methylation rate.

 

Sirtuins

 

Sirtuins are the net of signal proteins that work within the metabolic arrangement. This net is formed of 7 base proteins, which:

-Positively reinforce the epigenetics

-Help the metabolic process, including liver, pancreas, muscle and the fat tissue.

-Strengthen the neurological and cardiovascular functions.

-Prevent inflammation and help in the prevention of cancer

-Sirtuin proteins are used to repair the broken bits of the  DNA.

 

Studies with resveratrol, a SIRT1 activator, have shown that resveratrol can help to prolong life.

 

And it is proved that long bouts of hunger may lead to a higher number of sirtuins.

 

So, is it possible to slow down the aging process if one manages to activate their sirtuins? This is a question that is pondered by many investigators.

In 2016,  Nature published a research that speaks of a tie between sirtuins and NAD+.

It fully demonstrated the importance of sirtuins as an conserved regulator for longevity.

Interestingly enough, the presence of NAD+ is observed to go down with age, which drops the sirtuin activity, and affect the cellular wholeness and the mitochondria’s working order.

The supplied provision of NAD+’s key ingredients to reduce these age-related problems is currently receiving significant attention. This article describes these important aspects of the close link between NAD+ and sirtuins in aging/longevity control. NAD can be taken as an external support, but the use of resveratrol, long bouts of fasting, short-term ketogenic diet and heat changes in the environment such as hot-cold shows, saunas, and even ice also increase NAD.

One of the best examples for prospective cohort for cardiovascular disease is a famous study known as the Framingham study.

 

Framingham study has shown that postmenopausal women are a bout 2 to 6 times more susceptible to cardiovascular diseases compared to premenopausal women

 

Recent studies have proved that the SIRT1 function holds an important role in modulating vascular aging.

 

Estrogen protects the body against visceral lubrication.

 

A reduction in central body fat has been seem in hormone replacement therapy in postmenopausal women with low estrogen levels.

 

Estrogen exerts its physiological effects through estrogen receptors on target cells, including adipocytes. Studies show that estrogen protects against fatty inflammation and fibrosis even before the onset of obesity.

 

In other words, contrary to what is known in the society, menopause is the cause of pathological lubrication, not bioidentical hormone therapy. Hormone replacement therapy seems to be the solution.

 

 

mTOR

 

The mTOR path is directly involved with both cancer and aging.

Mutations that result in activation of the mTOR pathway are involved in oncogenic transformation when protective mechanisms in the cell cycle are disabled. When mTOR is activated again and the cell cycle is stopped, the cells enter the aging state.

Rapamycin and other rapalogs inhibit mTOR complex 1 and suppress such geroconversion.

 

Theorically, if mTOR is slowed down, a lengthier life may be achieved. And if the mTOR increase cannot be manipulated, aging is ultimately inescapable.

 

In this study, the mTOR pathway has a role in regulating the hallmarks of aging such as protein intake adequacy, energy homeostasis, cellular senescence, stem cell and proteostasis.

 

TOR (target of rapamycin), which plays an important role in cell growth, is an anti-fungal substance that reduces the rate of aging by specifically inhibiting the protein called MTOR. It got its name from Rapa Nui, the original name of the Easter Island where it was discovered.

Rapamycin treatment inhibits mTOR signaling and cells enter a reversible quiescent state.

I would like to point out that the presence of mTOR is also effective in destroying cancer cells that need to be destroyed or cells that are worn out from inflammation or toxicity, and it is not correct to completely destroy them in this sense.

 

 

 

Mitochondria

 

The mitochondria are an organelle that are largely known to be the powerhouse of the cell. It owns a unique core that is separate from the core of the cell itself, which seems to be passed down from the mother. It procures the required energy for the cell, so it is quite important for a proper, healthy life.

 

A decent bit of the aging process can be traced back to mitochondrial functions breaking down, and the genetical defects slowly stacking up over time.

In all fairness, the faulty bits of the mitochondria and the core of the cell may be directly allocated to the reason why aging even happens.

It’s a well-regarded fact that cardiovascular sicknesses tend to get more common after menopause takes place. Mitochondria that undergo quality control through mitochondrial autophagy play a crucial role in the regulation of cellular senescence.

 

The aim of a study published in 2021 was to investigate whether the effect of estrogen-mediated protection against aging on arteries is linked to the induction of mitochondrial autophagy. E2-induced mitochondrial autophagy has been found to play a crucial role in delaying vascular senescence.

 

It has been proven that the replacement of estrogen, which we no longer secrete, in bioidentical form with menopause, protects us against vascular aging by providing healthy mitochondrial autophagy.

 

 

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