The 9 Hallmarks of Aging

Cracking the Aging Code: Understanding the 9 Hallmarks You Never Knew About.

Breaking Down The Aging Process

In 1991, the book "Evolutionary Biology of Aging" provided a definition of aging as a decline in an organism's fitness components due to physiological deterioration. However, aging is a complex process, and there is no single explanation for why it occurs.

In the past 30 years, scientific interest in aging research has grown, focusing on the cellular and molecular basis of aging. A review published in Cell by Carlos Lopez-Otín and his team proposed nine hallmarks of aging that contribute to the aging process. Each of these hallmarks plays a role in the aging process, and understanding them can help us make healthier choices for healthy aging.

What are the 9 hallmarks of aging?

1. Genomic instability 

It is evident that your DNA holds immense significance, and safeguarding it should come as no surprise. Functioning as the blueprint for your body, DNA plays a crucial role in orchestrating every aspect of your bodily functions.

Your cells are well aware of the importance of DNA and have evolved to protect it by surrounding it with sturdy walls, shielding it from the detrimental forces that may pose a threat.

However, despite the diligent efforts of your cells, your DNA is constantly exposed to various damaging factors. Free radicals, pollutants, pesticides, and UV rays from the sun all contribute to the potential harm inflicted upon your DNA.

The American Federation of Aging Research reveals that your DNA undergoes damage a staggering one million times per day.

Fortunately, your DNA possesses an innate ability to repair itself and combat these aggressors. Nonetheless, the repair process can only address damage to a certain extent. As you age, the accumulation of DNA damage – referred to as genomic instability – becomes inevitable.

Furthermore, mutations can also be inherited during the DNA repair process, further impairing the integrity of your DNA.

The connection between aging and genomic instability can be likened to the lifespan of a diligently maintained car. While you may be meticulous in regularly rotating your tires, changing the oil, checking tire pressure, and

2. Telomere attrition

Telomere attrition is a specific type of genomic instability that has garnered significant attention in recent research, distinguishing it among the nine hallmarks of aging.

Telomeres, which can be likened to the protective plastic caps at the end of shoelaces, are located at the end of each chromosome.

In order to comprehend why telomeres are extensively studied in research on aging, one must consider how DNA replicates.

With each instance of cell division, a portion of telomeres is gradually eroded, resulting in their progressive shortening. This means that every time a cell replicates, the telomeres become shorter.

Ultimately, as the telomeres reach their limit, there is no more capacity for further reduction. Consequently, cells become incapable of dividing, hastening the process of aging.

Given the finite nature of telomere length, researchers have investigated its correlation with lifespan. A study cited in the Proceedings of the National Academy of Sciences analyzed telomere length across various species.

The study's conclusion states, "The results presented here indicate that the rate at which telomeres shorten in a species can be utilized to predict the lifespan of that species..."

The discovery of telomeres has revolutionized our understanding of aging, prompting researchers to consider factors beyond our chronological age. The impact of this research was so profound that the scientists involved were awarded the Nobel Prize.

3. Epigenetic alterations 

The focus of aging research extends beyond DNA to encompass other crucial factors such as the epigenome.

While every cell in the body possesses the same DNA, the diverse functions performed by different cells stem from variations in their epigenomes.

The epigenome consists of various chemical compounds that instruct the DNA on its activities, akin to a contractor executing a blueprint. This process, called gene expression, determines what each cell will become. For instance, in the case of liver cells, the epigenome activates specific regions of the DNA to assign the cell its liver-related functions.

Unfortunately, as we age, the epigenome can be affected by external factors and illness, leading to changes in gene expression and altering how the epigenome works with the DNA.

A study published in the Journal of Applied Physiology identifies epigenetic modifications, such as mutations and deletions, as prominent causes of genomic instability.

It is evident that the interplay between the epigenome and DNA is essential, as research on epigenetic changes and aging underscores their intrinsic connection to the fundamental characteristics of aging.

4. Loss of proteostasis 

Proteostasis originates from the etymology of "protein" and "stasis," denoting a state of equilibrium. It is the process by which the body maintains a stable synthesis of proteins with no complications. Loss of proteostasis refers to the malfunctioning of this essential protein-building machinery.

Proteins play a crucial role in the cell, ranging from regulating cellular walls to acting as catalysts in major chemical reactions within the body.

The body achieves proteostasis through a network of proteins, but errors can sometimes result in either an inadequate or excessive production of proteins. These errors can cause disruptions in the network, leading to the formation of misshapen and dysfunctional proteins, comparable to a paper jam in a printer.

According to a review in the journal Nature Reviews Molecular Cell Biology, environmental factors can induce stress on the protein-building system, increasing the occurrence of these errors over time.

The abstract highlights, "Maintaining a balance in the proteome, despite the accumulation of external and internal stresses during the aging process, is a challenging endeavor. These stresses contribute to the decline in both the capacity and integrity of the proteostasis network."

Episodes of oxidative stress, which arise from an imbalance between free radicals and antioxidants in the body, can intensify the frequency at which these protein production errors occur. Similar to oxidative stress, there must be a harmonious balance between protein synthesis and degradation.

A research article published in the Proceedings of the National Academy of Sciences confirms that the tipping point occurs when the replenishment of functional proteins can no longer keep up with the depletion caused by misfolding, aggregation, and damage.

5. Deregulated nutrient sensing 

The functioning of your cells relies on nutrients obtained from the food you consume. However, the availability of these nutrients may fluctuate as you do not eat continuously throughout the day. To address this, your cells possess sensors that can detect changes in nutrient levels within your body. These sensors play a crucial role in maintaining the appropriate balance of nutrient intake.

Metabolism, the process of converting food into energy, can be likened to a double-edged sword. While it provides energy, it also results in the creation of harmful byproducts called free radicals. This is similar to how a gasoline engine powers a car efficiently but emits carbon emissions.

The nutrient sensors in your cells prevent excessive or insufficient intake of nutrients from the food you consume. However, accumulated damage from oxidative stress over time can impair the effectiveness of these sensors in regulating nutrient intake.

An article published in Communications Biology has emphasized that these nutrient sensors form the molecular basis for the connection between lifestyle habits and aging.

As the damage to your nutrient sensors increases, so does the damage caused by over metabolizing. This creates a vicious cycle of damage within your body.

Nevertheless, ongoing research on nutrient sensing, particularly in relation to caloric deficits, holds significant potential in the field of aging research. A review published in Nature highlights the positive impact that studying nutrient-sensing and caloric restriction can have on aging:

"On the other hand, limitation in nutrient intake, or caloric restriction, has proven to be one of the most successful interventions against the onset of aging. Therefore, understanding the mechanisms involved in normal nutrient sensing is essential in order to develop better interventions..."

6. Mitochondrial dysfunction

The mitochondria, often referred to as the cell's "powerhouse," play a crucial role in generating the necessary energy for your cells. They make up the main component of metabolism and are responsible for producing 90% of your body's energy.

However, this energy production comes with a price. According to a review published in the Journal of Signal Transduction, mitochondria also produce the majority of free radicals in the cell as a byproduct of their metabolic processes.

This cycle of damage extends to the mitochondria itself, affecting their efficiency. The free radicals generated in the process lead to overworking of the mitochondria's systems, which further produces more free radicals.

As you age, research from the School of Kinesiology and Health Science at York University suggests that the production of mitochondria decreases. This means that the few remaining mitochondria have to work harder to compensate.

The loss of mitochondrial function can result in excess fatigue, a common symptom associated with aging, as highlighted by Integrative Medicine.

However, mitochondria are responsive to the body's energy demands. Similar to a power grid, if there is a decrease in energy demand, some power plants shut off for efficiency. Sedentary lifestyles can lead to further decline in mitochondrial function as the body adapts to lower energy needs.

Fortunately, the opposite is also true. A study conducted by David A. Hood from York University reveals that exercise can stimulate mitochondrial biogenesis, the process of creating more mitochondria to meet the increased energy demands.

In conclusion, the mitochondria serve as the primary source of energy for our cells. While they generate energy, they also produce free radicals. The damage caused by free radicals affects the efficiency of mitochondria and can lead to fatigue. However, the body has the ability to adapt by creating more mitochondria in response to increased energy demands through exercise.

7. Cellular senescence 

Cellular senescence refers to the state in which a cell loses its ability to divide, ultimately leading to its demise.

This process is a natural occurrence and can be seen as a protective mechanism for the body.

When a cell sustains irreversible DNA damage or telomere dysfunction, cellular senescence prevents the spread of these damaged traits. It acts as a last resort when the body is exposed to various environmental stressors.

However, as we age, the number of senescent cells increases. Researchers have discovered evidence suggesting that cellular senescence plays a role in age-related conditions.

Without the replacement of new cells, an abundance of senescent cells can cause issues such as a loss of tissue-repair capacity and the production of proinflammatory molecules.

Nevertheless, extensive research is being done to understand the mechanisms behind cellular senescence and its potential for positive therapeutic interventions.

Some studies have found that cellular senescence has beneficial effects in suppressing tumors, but more investigation is needed to fully comprehend and harness these benefits.

8. Stem cell exhaustion

In recent decades, stem cell research has gained significant attention in both the media and scientific community. This is due to the intriguing nature of stem cells, which hold both promise and controversy.

One of the key benefits of stem cell research is its ability to facilitate the growth of new tissue in humans. However, the use of embryos in the initial stages of research sparked political disagreement, leading to controversy.

Fortunately, recent advancements in stem cell research have allowed scientists to bypass the use of embryos by utilizing adult stem cells instead.

To comprehend the functioning of stem cells, we must delve into the epigenome and its role in controlling genes. The epigenome is responsible for assigning specific roles to our cells. Each type of cell in our body, such as skin cells, liver cells, brain cells, and heart cells, has its own unique function. In contrast, stem cells are like fresh college graduates, capable of taking on various responsibilities within the cellular workforce of our bodies.

Based on the needs of our body, stem cells have the ability to transform into a specific cell type. They act as reinforcements, adjusting their specialization to meet the demand for specific cells. For example, if our body requires more liver cells, stem cells can adapt and become liver cells.

This process of cell replenishment plays a crucial role in tissue homeostasis and regeneration. Stem cell exhaustion occurs when the replenishment of cells cannot keep pace with the retiring cells, leading to a decline in tissue function. Stem cell exhaustion is closely connected to the other signs of aging. Imbalances between stem cells and retiring cells can arise from the accumulation of senescent cells, primarily caused by DNA damage.

A review published in Cell Metabolism emphasizes the impact of age-related cell-cycle defects, DNA damage, and chromosome disorganization on the functional activity of hematopoietic stem cells (HSCs). These issues can result in decreased blood production and diminished therapeutic potential in transplantation assays.

While much more research is needed to fully grasp the potential capabilities of stem cells, their significance in the aging process is evident. Aging research necessitates the consideration of stem cells alongside other aging markers.

9. Altered intercellular communication

Your cells engage in communication through a complex network of chemical signals. This enables them to collaborate in responding to changes in their environment and carry out the intricate processes required of a multicellular organism, such as humans.

However, as you grow older, this communication network begins to deteriorate. The signals become weaker and the communication becomes disrupted, a condition known as altered intercellular communication.

One of the main causes of this degradation is inflammation. Inflammation is a natural response by your body to remove threats and damaged cells. However, there are times when inflammation gets out of control and causes harm to healthy cells nearby.

What triggers this inflammation? One of the main culprits is the presence of senescent cells, which are old cells that can no longer replicate. These senescent cells release chemicals that cause inflammation and further damage the cellular environment.

Certain studies suggest that senescent cells can use the same signals of intercellular communication to convert nearby healthy cells into senescent cells. In an article published in Trends in Cell Biology, it is proposed that the accumulation of senescent cells and their active intercellular communication profile is a consequence of aging and related diseases.

Research on altered intercellular communication challenges the notion that only autonomous cells are affected by molecular aging. While there is still much to learn about the intricacies of this chemical signaling network, studies on intercellular communication demonstrate how aging can be influenced by both individual cells and their surrounding environment.