Epigenetics Changes with Aging & How Can We Positively Utilize It?

[dropcap]H[/dropcap]ave you ever wondered why those identical twins, who originate from the same DNA and may or may not have similar faces, turn out so different? Or even why does one twin have health issues at a younger age while the other one has the perfect health and mind? A precise and deeper answer can be found in something called epigenetics.

What is Epigenetics?

It is the study of how DNA interacts with multitudes of smaller molecules. Found within cells, which can activate and deactivate genes. Epigenetics explains why brain and muscle cells seem different from skin cells. Basically, the DNA of all three cell types is identical, but their genes are expressed differently, resulting in the presence of three separate cell types. There may be more about you that can be deduced from your DNA than just your appearance. The genetic theory of ageing states that your life expectancy is determined by your genes (and any mutations in those genes).

To further grasp this concept, think of your DNA as a cookbook; the molecules it contains are mostly responsible for dictating what food is prepared and at what time. They are not making conscious choices; their presence and focus within the cell create the difference. The expression of genes and DNA occurs when they are read and transcribed into RNA, which is then translated into proteins by ribosomes. And proteins are mostly responsible for determining the properties and function of a cell. This regulation ensures that each cell only generates the proteins required for its activity. For example, bone-promoting proteins are not synthesized by muscle cells.

Epigenetic Changes.

Epigenetic changes are structural changes to DNA that control the activation of genes. These alterations are bonded to DNA and do not modify the sequence of DNA building blocks. Because epigenetic modifications govern whether genes are active or inactive, they influence the production of proteins in cells.

In contrast to genetic changes, epigenetic changes can be reversed and do not alter the DNA sequence but can alter how the body interprets the DNA sequence. All genes in all cell types are activated or silenced by an underlying interaction between the epigenetic processes mentioned below.

DNA Methylation:

DNA methylation is a common way that the environment can alter genes. DNA methylation is attaching small chemical groups called methyl groups to DNA building blocks. Your DNA consists of four bases: cytosine, guanine, adenine, and thymine. A chemical unit called a methyl group, which contains one carbon and three hydrogen atoms, can be added to cytosine. When this happens, that area of the DNA is methylated, that gene is turned off or silenced, and no protein is made from that gene.

Changes in DNA methylation patterns occur throughout a person’s lifetime. The process is more prevalent during early development and later life. In early life, these alternates help organs and tissue form appropriately as DNA methylation process involves several metabolic gears that produce necessary methyl groups for the methylation process. Each component or gear in the methylation cycle is important for the process to continue and several nutrients are required. If this cycle doesn’t work properly, the methylation process is disrupted

Histone Modification:

Histone modification is another epigenetic alteration. Nucleosomes are DNA’s building blocks and are arranged in chromosomes like beads on a necklace. The histone proteins that make up each nucleosome enclose a strand of DNA. Eight histone proteins make up each nucleosome (2 copies each of histones H2A, H2B, H3, and H4). When these histones are wrapped tightly around DNA, gene expression is hindered. Histone modification is trickier than DNA methylation. It has the following methods,

• Histone phosphorylation: Adding phosphate groups to histone amino acids.
• Histone methylation: This kind is the most intricate of the three. Many of the amino acids in histone proteins have methyl groups attached to them. Many amino acids can be transformed at once by adding methyl groups. Histone methylation involves several enzymes, indicating its complexity.
• Histone acetylation: Lysine modification by introducing or removing an acetyl group. When a histone is acetylated, it loses some of its positive charge and the DNA to which it is attached becomes less of an attractive force.

The alteration of histones is a very intricate and strictly regulated process. When histone modification patterns are changed, this might result in uncontrolled gene activation or gene silence. This can eventually result in the cell’s death or, more severely, cancer.

Non-Coding RNA: RNA-associated silencing is a kind of post-transcriptional gene modification in which the expression of one or more genes is silenced or downregulated by tiny non-coding sequences, also known as microRNAs.

Errors in the epigenetic process, such as incorrect gene modification or the inability to add a chemical group to a specific gene or histone, can result in aberrant gene activity or inactivity. Changes in gene activity, especially those resulting from epigenetic mistakes, are frequent causes of genetic diseases. Cancers, metabolic problems, and degenerative diseases have been identified to be associated with epigenetic abnormalities.

The Epigenetic Clock.

An individual’s biological age is an essential yet elusive term. From the time we reach early adulthood, our physical and mental abilities begin to deteriorate, although the rate at which this happens varies greatly across individuals. A person’s functional ability may be predicted more accurately by their biological age than by their chronological age, which is detected via a technique for detecting biological age.

That is when at the University of California, Los Angeles professor Steve Horvath discovered that the methylation process is a reliable indicator of biological age. More than 13,000 human samples were collected and analysed by Horvath and his colleagues. The team eventually arrived at an algorithm reliably predicting a person’s biological age.

Horvath introduced his now-famous epigenetic clock in 2013, and it has become widely utilised. This clock, and others like it, are intended to demonstrate the degree of organ degradation. This clock was developed (also referred to as “trained”) using thousands of healthy samples from 39 distinct datasets. These samples spanned a wide range of ages and 51 distinct tissues and cell types. Each of these samples was evaluated for 21,000 distinct CpG sites. As a result, this might aid in estimating how many healthy years a person still has ahead of them, but the reliability of such clocks is still up for discussion.

What other factors determine aging? Learn it in our article here.

Effect OF Epigenetic Changes.

The expanding evidence that epigenetic pathways underlie a vast array of diseases, behaviors, and other health difficulties has driven interest in epigenetics. Many different disorders have recently been linked to epigenetic alterations. This category includes various cancers and respiratory, cardiovascular, autoimmune, reproductive, and neurological diseases. It is believed that several causes might trigger epigenetic alterations.

• Aging: Due to repeated exposure to harmful environmental conditions, our cells’ epigenomes get permanently altered with age. These alterations add up over time and have been linked to the deterioration of aged cells.

Your epigenetics at birth differs from your epigenetics as a child or an adult and evolve throughout life. As proven in a 2012 report, the association between DNA methylation and age was studied. Millions of DNA methylation sites were measured in a baby, a 26-year-old, and a 103-year-old. It was found that older individuals showed less methylated DNA than babies. People approximately 26 years old showed DNA methylation levels between those of neonates and elderly men, indicating that DNA methylation slows with age. As a result, genes previously silenced by methylation DNA become activated, potentially leading to various disorders.

• Pregnancy: The epigenetics of an unborn child can be altered by the mother’s lifestyle and surroundings during pregnancy. These alterations may increase the child’s susceptibility to certain illnesses for decades. During the Dutch Hunger Famine, Heart disease, schizophrenia, and type 2 diabetes were all more common in those whose mothers were pregnant with them during the famine. 60 years after the famine ended, researchers studied methylation levels among individuals whose mothers were pregnant. (1) (2) (3). These individuals had increased methylation at certain genes and reduced methylation at others compared to their non-famine-born siblings. Variations in methylation may explain why these people had a higher chance of getting certain diseases later in life. (1) (2)
• Polymorphism: A very common effect of the methylation cycle slowing down is when a person has the variation of gene MTHFR, a variation of this gene causes the metabolism of folate to be changed. These changes are found in 40% of the population with an increased risk of cardiovascular disease and some cancers. This change can be more evident in people having two copies of polymorphism in the genetic code known as homozygous expression. This means that both parents have passed the polymorphic gene to the daughter cells. Having one polymorphic gene means the risk is disrupted, and methylation is reduced.
• Cancer: Cancer was the first human disease related to epigenetics in 1983. The DNA methylation levels were lower in colorectal cancer tissue compared to healthy tissue from the same individuals. Loss of DNA methylation can induce abnormally high gene activation by changing chromatin.  Meanwhile, excessive methylation can compromise the efficacy of tumour suppressor genes. A second example would be an epigenetic modification which “switches off” genes that help repair damaged DNA, resulting in an increase in DNA damage and a heightened risk of cancer.
• Neurological disorders: Certain neurodevelopmental problems are caused by epigenetics and gene mutations that result in dysfunctions. Here, we categorize them according to the mutated epigenetic machinery. Such as Fragile X syndrome is the most frequent inherited mental illness among men. This condition causes intellectual deficits, delayed linguistic development, and “autistic-like” behaviour. The syndrome is caused by an error in the FMR1 gene, which stands for “fragile X mental retardation 1.” People who do not have fragile X syndrome have between 6 and 50 copies of the three-letter sequence CGG in their FMR1 gene. Individuals with more than 200 repeats, on the other hand, have a full mutation and usually show signs of the syndrome.

About two decades ago, epigenetics began attracting scientists’ attention as a potential explanation for various puzzling biological occurrences. Patterns of epigenetic change vary between persons, tissues within an individual, and cells within a tissue. The epigenome can be affected by environmental factors such as a person’s nutrition and exposure to toxins. In some cases, epigenetic modifications can be passed from one cell to the next during cell division, and they can also be inherited from one generation to the next.

New scientific research demonstrates that environmental factors can change the expression of genes. In addition, scientists have revealed that early experiences can influence the activation and repression of genes and the expression of particular genes. Thus, the outdated notions that genes are “fixed in stone” and determine development have been disproven. Nature versus nurture is no longer a point of contention.

Diet, obesity, physical exercise, cigarette smoking, alcohol intake, environmental contaminants, psychological stress, and working night shifts are only few of the lifestyle variables thought to alter epigenetic patterns.

Interventions.

Many diseases, including cancer, are likely to include epigenetic alterations. Therefore, it makes sense to address these changes using anti-epigenetic therapies. These adjustments seem like a good place to start since, unlike mutations in the DNA sequence, they can be undone. Treatments that target DNA methylation or histone acetylation are particularly well-liked.

1. Diet: A diet rich in these foods may aid DNA methylation and suppress genes that aren’t needed. All of these can be bought as supplements, but it’s best to get as much of them as possible from food. Multiple studies indicate that certain vitamins and minerals play a role in DNA methylation. (1) (2).

Breast cancer research in women has included examinations of DNA methylation in tumour cells since at least 2014. Researchers showed that those who consumed the most alcohol had the lowest DNA methylation levels. On the other hand, those with high folate intake were more likely to have elevated methylation. These findings provide credence to the hypothesis that dietary factors influence DNA methylation. So, adding up these foods and nutrients can have a positive impact on your health as per research,

• Folate
• Vitamin B12.
• Vitamin B6,
• Vitamin B2.
• Magnesium.
• Betaine (also known as trimethylglycine).
• Vitamin D.

2. Meditation: Clearing your head for only 15 minutes a day has been shown to affect how your cells perform profoundly. Researchers at Harvard Medical School found that those who meditated for 15 minutes each day for eight weeks saw changes in 172 genes involved in inflammation, sleep-wake cycles, and sugar metabolism. In another research, mindfulness meditation has been demonstrated to affect particular kinds of DNA in breast cancer patients. Specifically, this form of meditation changed the length of telomeres, the protective caps at the ends of chromosomes.

3. Exercise: Exercise increases the expression of genes that stop cancers from developing and decreases the expression of genes that induce tumours to grow. In particular, walking has been linked to favourable epigenetic changes. The epigenetic change known as DNA methylation is significantly influenced by short-term and long-term exercise.

4. Epigenetic Reprograming:

New data reveals that epigenetic reprogramming can truly reverse the ageing process. Recent research on humans shows that a 12-month therapy with recombinant human growth hormone reduced the epigenetic age by around 2.5 years.

5. Epigenetic Drugs: As we understand the importance of epigenetic variables in illness, it becomes evident that they might be ideal therapeutic targets, especially because many can be modified. Epigenetic medications can repair gene expression abnormalities that cause illnesses. The primary emphasis of drug research has been their application in cancer therapy.  Two epigenetic medication kinds are being tested in this regard:

• Histone deacetylase (HDAC) inhibitors: These drugs make the chromatin structure less tight, which makes it possible for these genes to be turned on by transcription, which can impair tumour suppressor genes.
• DNA-methyltransferase (DNMT) inhibitors: They stop cancer cells from adding methyl groups to their genes. Azacitidine and decitabine are two drugs that stop DNA from getting methylated. They have been approved by the FDA and are used to treat blood cancer.

Because epigenetic modifications occur everywhere, epigenetic treatment must be utilised carefully. Epigenetic therapy must target aberrant cells. If they don’t, boosting gene transcription in normal cells might turn them malignant, causing the illnesses they seek to heal. Researchers are working to target aberrant cells without harming normal cells. This makes epigenetic therapy look more and more promising.

Calendar years may pass at the same rate for everyone. Still, it may seem that some people age much more slowly (or quickly) than others, with correspondingly variable rates of physical degeneration and exposure to health hazards. It’s possible that in the not-too-distant future, evaluating your DNA methylation profile and epigenetic changes will be as common as checking your blood pressure. However, specialists have yet to determine how best to interpret the findings of these tests so that the public may use them.