The 9 Hallmarks of Aging

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- Updated by Sarah Qaiser

Table of contents

Nine Hallmarks of Ageing

Genomic instability

Telomere attrition

Epigenetic alterations

Loss of proteostasis

Deregulated Nutrient sensing

Mitochondrial dysfunction

Cellular Senescence

Stem Cell Exhaustion

Altered intercellular communication

Finally

Key Takeaways

  • To understand how aging works, scientists have discovered that age depends on how much cellular damage is in our bodies, not necessarily on our age.
  • This cumulative damage can be marked by nine hallmarks, characterizing the fundamental aging process.
  • The first four hallmarks of aging are considered primary hallmarks as they are responsible for the other five hallmarks.
  • Genome instability is considered the most important hallmark, as chronic mutations at the cellular level can cause a domino effect of other hallmarks, resulting in aging.
  • Mitochondrial dysfunction is another key hallmark, as when mitochondria become impaired, they change, are unable to produce energy fully, and release damaging oxygen species.
  • Altered intercellular communication is another prominent hallmark. If the body has enough faulty communication between cells, it can cause tissue damage and cellular corruption, resulting in a higher chance of developing cancer and infection.
  • Natural substances such as NMN help promote mitochondrial health and help to counter some of the hallmarks of aging.

Aging is a complex process that is commonly defined as a time-dependent progressive loss of a person's physiological integrity that finally leads to reduced physical function. In summary, the accumulation of molecular and cellular damage over a person's lifetime leads to age-related clinical disorders, making them more susceptible to age-related diseases and, ultimately, death. Understanding the particular cellular and molecular pathways involved in aging is still one of the most difficult and important problems in biological research.

Scientists characterized the fundamental aging process as the nine hallmarks of aging roughly a decade ago, in the absence of a cohesive theory on aging. Because our bodies are dynamic, molecular machines, we realize that how we age is not determined by our chronological age, but by the cumulative damage that occurs within our bodies. With this context it’s clear that  we can positively impact the aging process with particular, healthy lifestyle choices which will make a big difference in how well we age and how long we live.

Nine Hallmarks of Ageing

Aging is a succession of events that inflict direct damage to our bodies, accumulate cellular waste, and result in genetic flaws, followed by ineffective reactions to and repairs these faults.

Ok. Even so, we still don't have a good understanding of what aging entails. What exactly are these losses? What kind of cellular waste is accumulating? Why do genetic faults occur, and why does the body react incorrectly? 

To understand all these ideas, we need to learn about the hallmarks of aging.

There are nine hallmarks of aging, or reasons we age, according to scientists. The following are the distinguishing features: 

    • Genomic Instability
      Hallmarks of again Cell
    • Telomere Attrition 
    • Epigenetic Alterations 
    • Loss of Proteostasis
    • Deregulated Nutrient Sensing
    • Dysfunction of the Mitochondrion
    • Cellular Senescence
    • Stem Cell Exhaustion
    • Altered Intercellular Communication

The first four hallmarks of aging are referred to be the primary hallmarks of aging because they are responsible for the next five hallmarks on the list. They are, in essence, the causes of the processes that cause us to age. Let's take a closer look at each of these characteristics and how they affect our lives to understand aging better.

Genomic instability

Genome instability is the most important primary hallmark of aging since it has so many implications on the aging process and even the development of some of the other hallmarks of aging. Smoke, pesticides, and other external agents, as well as basic DNA replication errors and oxidative stress, can harm our genome over time. Even though we have evolved a complex network of DNA repair systems, DNA damage accumulates over time, generating cell mutations and, in the worst-case scenario, cancer formation.

The first few mutations normally have no effect. However, these mutations can accumulate over time and cause serious damage. For example, if enough mutations occur in proto-oncogene genes, cells might become malignant and divide uncontrollably. 

Aging occurs when these cells accumulate so many mutations that they become dysfunctional. They should die by self-suicide, known as apoptosis at this time, but many cells evade this fate and enter another stage known as cellular senescence (which we'll discuss later). Even for the cells that do undergo apoptosis, if there are no cells to replace them, the tissues and organs they make up would eventually degenerate. On the other hand, if these mutations occur in the mitochondrial DNA (yep, the cell's powerhouses), mitochondrial malfunction can result (which is also another one of the hallmarks).

However, Genome instability can be treated with the help of NMN Supplements. It is noted NAD+ appears to be one of the major chemicals involved in DNA repair. Researchers have discovered a link between NAD+ depletion and DNA damage. It was discovered that refilling NAD+ levels by employing its precursor NMN improved the cell's ability to repair damaged DNA. However, more research and studies are needed in this area.

Telomere attrition

Telomeres are simply caps on the ends of chromosomes made up of thousands of repeats of the same DNA sequence. By acting as protective caps, the telomeres (pink) protect the coding areas of the chromosomes (purple).

Why are they important and how do they keep the DNA safe? 

They have two key functions: they safeguard coding DNA, and they maintain track of cellular age.

DNA's building units, also known as nucleotides, are highly reactive and can interact with other molecules. Telomere caps are generated at the ends of chromosomes to prevent chromosomes from connecting to other chromosomes or cellular components. Telomeres are not extended to their original length in most cells because they are cleaved division after division. 

This means that as a cell divides more and more, the length of the telomeres gets shorter and shorter until we run out of them. When this happens, the cell must cease dividing and change into a senescent cell to avoid cleaving coding DNA. Telomeres, in this fashion, effectively restrict cellular age or the number of cell divisions that can occur.

Telomere shortening has been observed in human and mice cells during normal aging. The fact that telomere length diminishes with age, contributing to normal cell senescence, raised the possibility that this could be a biological aging marker. To provide your cells with the building blocks they require, make sure you consume a nutritious diet and drink pure water. Choosing healthier selections can naturally help you lose weight and reduce inflammation, which is both linked to telomerase activity and telomere length reduction.

Targeting telomere attrition at the cellular level is one of the most effective strategies to combat it. NMN or NR, as well as various antioxidants, are natural supplements that can help with this.

Epigenetic alterations

You're aware of the various kinds of cells in your body. There are liver cells, neurons, muscle cells, immunological cells, and various other types of cells. Each one has a distinct function and a set of traits that are required to carry out that purpose. However, they all have the same genetic code. Every single one of the trillions of cells in our body has identical DNA. 

So, why do certain cells behave like neurons while others behave like muscle cells?

The epigenome is responsible for this. In programming terms, if DNA is the digital hardcode in our cells, the epigenome is the analog code that allows us to understand and use the DNA. You may be perplexed how our numerous tissues and organs can appear so dissimilar, given that the genetic information recorded in our DNA is identical in all cells of our body. 

In fact, epigenetic information is added to DNA, which increases or suppresses the expression of specific genes as necessary by distinct tissue types. If a cell is to become a liver cell, epigenetic alterations will ensure that just the sections of the genome particular to liver cells are expressed, while the parts specific to other cell types are ignored.

This epigenetic information might be lost as we become older. Different enzymes that govern this information may cease to operate properly, resulting in genome misregulation. As a result, genes that should be suppressed occasionally become active, and vice versa. The cell is termed to be ex-differentiated at this time. And the loss of information and cell function is a crucial factor in the aging process.

Again, lifestyle and environmental factors can influence epigenetics in a positive or negative way. Epigenetic alterations can be avoided by eating a nutritious diet, exercising regularly, and taking natural supplements.

Loss of proteostasis

Protein homeostasis, or proteostasis, is a process in which proteins are constantly generated and destroyed in our cells. Proteins are like tools that must be put together correctly in order to execute their many critical cellular activities, and folding proteins into the proper shapes is an important component of that process. Damaged or aggregated protein components induce malfunction or even cell toxicity when these systems grow less efficient over time.

Mutations in DNA and RNA can result in erroneous protein sequences, resulting in defective proteins or even cell death. Overall, the loss of proteostasis has profoundly bad health consequences in our cells and bodies and is yet another major contributor to aging. Changes in one's lifestyle come into play again, and protein production is more stable when you work out regularly. Natural substances that support proteostasis and assist the body cope with environmental stressors are also beneficial.

Deregulated Nutrient sensing 

When nutrients are plentiful, cells and tissues store energy and develop, and when nutrients are few, homeostasis and repair processes are activated. As a result of the deregulation of the nutrient-sensing pathway, cells fail to respond appropriately to the cues that typically regulate energy production, cell proliferation, and other critical cell processes. There are four key nutrient-controlled mechanisms in our cells that regulate metabolism and contribute to aging. IGF-1, mTOR, sirtuins, and AMPK are the four main protein families linked to these processes. To control deregulated nutrient sensing, you can use calorie restriction, well-known for its lifespan and health advantages. Because it decreases IIS and mTOR while activating AMPK and Sirtuins, it's one of the most effective approaches to avoid age-related illnesses. The goal is to cut calories by 10% to 30% while still meeting your daily nutritional requirements.

Mitochondrial dysfunction

The mitochondria are the cell's "powerhouse." They act as the principal component of metabolism, generating all of the energy your cells require. Your mitochondria are responsible for 90 percent of your body's energy production.

However, vitality comes at a price. As a result of their metabolic engines, mitochondria produce the majority of the cell's free radicals. The mitochondria are affected by the same vicious cycle of damage as occurs in your cell's nutrition sensors. Your mitochondria's efficiency is harmed by free radicals, which overwork their systems and produce more free radicals in the process. It is well known that as you become older, you produce fewer mitochondria.

Anyway, as we age, our mitochondria can become damaged and undergo changes that impair our ability to produce energy while allowing the release of damaging, reactive oxygen species, which, as we previously stated, can induce mutations in the cell's DNA and even disrupt proteostasis. Muscle weakness, inflammation, bone frailty, senescent cell burden, and immunological suppression have all been linked to reactive oxygen species, all of the aging symptoms.

Once again, the food we eat and the way we live have a significant impact on the health of our mitochondria. A nutritious diet rich in antioxidants and healthy fats will supply the body with all it requires to promote mitochondrial function.

You can also use the natural substance NMN that promotes mitochondrial health.

This compound is a precursor to NAD, a chemical that is essential for cell activity. Sirtuins, a family of proteins that aid mitochondrial health, cannot function correctly without NAD. One of the most effective strategies to strengthen your cells is to include NMN in your regular health supplement regimen.

Cellular Senescence

Senescence is a biological reaction that prevents old or damaged cells from proliferating. Senescent cells do not divide or maintain the tissues in which they are found and instead lie dormant. On the other hand, senescent cells release harmful chemical signals that encourage nearby healthy cells to enter senescence as well, resulting in a variety of health issues such as decreased tissue repair, increased chronic inflammation, and even an increased risk of cancer and other age-related diseases.

Many longevity researchers have looked at the possibility of identifying and deleting senescent cells in order to slow down the aging process. They discovered that removing just 30% of senescent cells was adequate to slow down age-related decline and ill health in mice, allowing them to live longer and healthier lives.

Stem Cell Exhaustion

Stem cells are essentially new cells that do not have the same amount of epigenetic regulation as other cells and do not yet have any distinct activities. Rather, they wait for chemical signals from the environment to tell them to differentiate into a certain cell type and begin performing those duties. As a result, stem cells are referred to as undifferentiated cells.

When particular cells in the body are injured, stem cells can develop into those cell types and replace them, keeping the body healthy.

What causes stem cell exhaustion?

Senescent cells' signaling and other inflammatory signaling pathways generate inflammation and limit stem cell activity, resulting in immunological senescence and tissue regeneration.

Stem cells can also suffer from telomere attrition and genetic alterations, both of which can impair stem cell activity in the long run.

Altered intercellular communication

Our cells must continually communicate with one another in order to grow and operate normally, secreting signaling molecules to surrounding cells or even sending chemical messengers via the bloodstream to affect cells and tissues far away. Aging affects both the signals sent by cells and the ability to receive calls to respond to those signals. This faulty communication causes complications such as chronic tissue inflammation and the immune system's failure to recognize and clear pathogens or defective cells, making the body more susceptible to infection and cancer.

Finally

Do you believe that aging can be reversed? Absolutely! There are a growing community of people who think aging is just another sickness like cancer, alzheimer's, or even the flu. And, like all other illnesses, we see a future in which aging does not have as much hold over society as it does now. 

While our understanding of these hallmarks of aging is still limited, scientists and biotech entrepreneurs are optimistic that they will lead to novel healthspan-promoting methods. 

Reference

https://www.globenewswire.com/en/news-release/2021/03/23/2198117/0/en/SRW-Founder-Unlocks-Inner-Youthfulness-By-Harnessing-the-Nine-Hallmarks-of-Aging.html

http://geroscience.com/hallmarks-aging/

https://medium.com/lotus-fruit/the-hallmarks-of-aging-d0b355304ef1

https://www.cell.com/cell/pdf/S0092-8674(13)00645-4.pdf

https://www.longevity.technology/hallmarks-of-aging/

https://www.frontiersin.org/articles/10.3389/fendo.2018.00258/full

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174/