The Nine Hallmarks of Aging

Biological Aging: An influence of genetics, stress, and of course, time

As a society, we tend to think of aging as a negative and something to dread. While we won’t get into why that’s a bad take on a societal level, we can’t deny that aging does have drastic effects on your physical wellbeing and ability to bounce back.

When you think of your age, you likely think about how many years you’ve been earth-side as a living, breathing person. This is known as chronological age; and while this is the most literal way of counting years, there is another term creating some buzz lately: biological age. As you can imagine, this is a bit more complicated to nail down. This is because biological age depends on much, much more than just the number of birthdays you’ve celebrated. 

When you think of biological aging, you can think of it simply as how your internal systems and physical health are faring as you age chronologically. Some factors that contribute to biological age include yes, your chronological age but also: genetics, lifestyle, nutrition and disease.

Hallmarks of biological aging: a glimpse at the future of aging research

Biological aging is the general understanding that there are some common events that happen at the cellular level as we age. These are considered the “hallmarks of biological aging,” which have been divided into nine subcategories. 

The culmination of one or more of these biomarkers determines your biological age. Unfortunately it’s not as simple as an swab test to figure this out for yourself–-generally this must be done with a visit to a doctor with a blood test at minimum. More on that later!

1. Genetic Instability

You may remember we recently discussed the relationship between the human genome and cellular health! There, we went over how our genes experience a myriad of changes as well as various amounts of wear and tear as the years go on. Genetic damage can occur over several years, which can result from DNA replication errors, oxidative stress, and external agents in the environment such as toxins. As genetic damage accumulates, the stability of genes weakens, putting them at risk for impairing other functions in your body, like your immune system and others, a notable hallmark for aging.

2. The Shortening of Telomeres

You may or may not know that at the end of chromosomes are protective caps made up of repeating nucleotide bases, called telomeres. These are sort of like the plastic cap found at the end of a shoelace, protecting the shoelace from damage and making it easier to lace up your new sneakers. In terms of chromosomes and DNA, they act the same; preserving their function. Over time, cell division and environmental damage cause telomeres to shorten, which is thought to be crucial in the aging process. 

Some scientists have proposed that telomere length may reflect one’s approximate “biological age" because as long as the telomere length is preserved, it seems that cells can continue to divide as they need, avoiding the dreaded cellular senescence. 

3. Epigenetic Changes

A fascinating discovery in science was that genes, once thought to be fixed and unchangeable, can actually change over time in response to their environment. Epigenetics focuses on how your behavior and environment influence the way your genes function. One feature of epigenetic change is the idea of histone modifications. Histones are small proteins that keep your DNA tightly wound and safe from threats in the cellular environment, as well as regulate access to genetic information. 

When small chemical structures called methyl groups are added to DNA, they shut down the corresponding gene, thereby modifying histone function. Think of methyl groups as the “on-and-off” switch of your genes: when they are added, genes turn off, when they are removed, genes turn on. This is called DNA methylation.

A diet that contains a large amount of methyl groups in their chemical composition may lead to a higher rate of DNA methylation, increasing the rate of gene inactivation. Of course, the reverse remains true as well—not getting enough methyl donor groups in your diet may lead to higher rates of genetic activation, leading to chronic inflammation and age-related disease.

4. Loss of Protein Homeostasis

Proteomes are the microbiological collection of cellular machinery required to synthesize and repair proteins in the body. When functioning properly, proteins are created and repaired to a high degree of accuracy, maintaining their integral protein function overall.

However as we age, it's apparent that proteomes begin to lose their function, which can lead to the accumulation of misfolded and damaged proteins. This is known to generate inflammation in the body, which can contribute to age-related disease such as Alzheimer’s disease, Parkinson’s disease, and eye-related dysfunction like cataracts. Notably, researchers are beginning to discover molecular complexes, like the ubiquitin-protease system, may be fundamental in maintaining proteome activity throughout the lifespan, which may help in the fight against aging.

5. Impaired Nutrient-Sensing Capabilities

Energy homeostasis is one of the most important physiological systems in the body that is necessary for optimal health. This includes the hormone insulin and insulin growth factor. In fact, the two of these compounds together make up the insulin and IGF-1 signaling (the IIS) pathway, highly known for its influence on age-related processes. Interestingly, genetic changes that reduce the function of the ISS pathway are associated with increased longevity. Regulating dietary pattern via dietary restriction practices can preserve IIS pathway function and improve lifespan and healthspan.

6. Mitochondrial Dysfunction

Perhaps begrudgingly, we all know the mitochondria is the powerhouse of the cell; equivalent to the engine of a car. If the engine dies, the car doesn’t run…the same goes for your cells. If the mitochondria begin to lose their ability to produce energy for the cell, the cell struggles to survive and begins to tap into limited energy reserves. It is important to maintain a sufficient antioxidant status in the body, as reactive oxygen species (ROS) are the enemy of mitochondria. Over time, the foods we eat and the level of exercise we partake in can both influence the relative levels of ROS in the body.

7. Cellular Senescence 

As hinted to previously in the context of telomeres, cells gradually lose their ability to replicate over time. When cells lack the ability to replicate but continue to function, they remain in a state of cellular senescence. Senescence tends to occur as we age because cells grow old and become victims of environmental damage as well as wear and tear.

To prevent the replication of their damaged DNA while retaining energy production and homeostasis, senescence kicks in to halt the replication cycle. But a problem arises when senescent cells begin to accumulate, because these cells trigger inflammation. Because aging organisms tend to lose their ability to clear these cells over time, senescent cells can be a primary source of chronic inflammation and therefore, biological aging.  

8. Exhaustion of Stem Cells

Stem cells contribute to the growth of the adaptive immune system, which is essential to produce antibodies to various pathogens we encounter throughout life. In this respect, if the body’s inventory of immune stem cells begins to deplete, it loses the ability to adapt to pathogens (called immunosenescence) and becomes susceptible to repeat infections from similar pathogens.

This is one of the reasons why it's so important to maintain good health as we age because seemingly simple pathogens like the flu virus can have detrimental effects on our systems later on in life. Notably, recent advances in science are suggesting that stem cell rejuvenation may provide the ability to reverse age-related processes in a whole organism, including immune-related functions.

9. Abnormal Intercellular Communication

Over time, the ability of cells to communicate to one another tends to decline. Because it is a common contributor to age-related diseases, let’s take the immune system as an example. Immune cells communicate with one another to regulate the response to a pathogen or cellular threat, and this communication is typically coordinated by small immune proteins called cytokines. For more on how this communication works, we covered it more in depth here. 

As expected, a healthy immune system will carry out the necessary processes naturally and efficiently, to keep inflammation at bay. However, frequent challenges to the immune response and chronic stress over the lifespan can dampen its ability to control pro-inflammatory signals, and as a result, a chronic, inflammatory continuum arises. This age-related increase in low-grade inflammation is termed “inflammaging,” and is considered to be a hallmark contributor to biological aging.

How Can I Find Out My Biological Age?

Let's blow out the birthday cake candles and wrap this up. Now that you’re aware of the Nine Hallmarks of Aging, you may be interested in finding out your own biological age. As mentioned, this is a relatively new idea and these tests can be pricey. However, if you enter your chronological age and nine blood markers from a recent test at the doctor’s with this tool, you can get a pretty accurate idea of your biological age. While most people are within about five years of their chronological age, researchers have seen outliers with up to a ten year discrepancy. We hope this helped wrap your head around some important health markers to keep an eye on as you experience life's little moments with each year that passes. Just don't forget to sit back and enjoy them. 

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