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April 11, 2023

12 Powerful Hallmarks of Aging

hallmarks of aging
Photo courtesy of Pixabay

Our aim with this website is to help you live younger longer. The topics and interventions we discuss will help you accomplish that, yet you still may fall short of reaching the maximal age possible for you. Some experts think we can make age 90 the new 40 or even 100 years old the new 30 as we uncover more and more about the mystery of aging.

Scientists have identified 12 hallmarks of aging. These hallmarks represent cellular and molecular changes that accumulate over time and thought to play a role in the aging process. Lifestyle goes a long way in minimizing the negative impact of these hallmarks of aging. Therefore, you have a major voice in how well you age.

We believe healthy aging is dying as the slowest rate possible. We appear to be programmed to live 120 years. This is called the Hayflick limit which states a cell can only divide a certain number of times. For instance, stems cells are felt to be able to divide 40 to 60 times. Based on this number of cellular divisions, it has been determined that 120 years of life is possible.

Obviously a vast majority of the population never makes it to 120. Why? The hallmarks of aging explain that.

So what are the hallmarks of aging?

12 Hallmarks of Aging

Nine of the 12 hallmarks of aging were identified in 2013 and three more hallmarks have been recently identified. Each hallmark may accelerate the rate of aging independently but some are interconnected through a variety of mechanisms.

The 12 hallmarks of aging are:

  1. Genomic Instability
  2. Telomere Attrition
  3. Epigenetic Alterations
  4. Loss of Proteostasis
  5. Deregulated Nutrient Sensing
  6. Mitochondrial Dysfunction
  7. Cellular Senescence
  8. Stem Cell Exhaustion
  9. Altered Intercellular Communication
  10. Chronic Inflammation
  11. Disabled Macroautophagy
  12. Dysbiosis

We have discussed five of these hallmarks directly or indirectly in previous posts which we have linked to under the 12 hallmarks of aging.

Chronic inflammation (which we have several posts on), disabled macroautophagy, and dysbiosis are the three most recent hallmarks of aging identified.

We will now go through these 12 hallmarks and describe what they are.

Genomic Instability

Genomic instability represents the accumulation of genetic damage/changes to our DNA that have occurred with time. There are external and internal factors that contribute to genetic instability. Radiation exposure is an example of an external factor as is exposure to any number of toxins we find in our environment.

To give you an idea of what we are exposed to take these numbers into account.

  • 85,000: the number of synthetic chemicals that have been manufactured since World War II and present in our homes and places of employment.
  • 2,000: the number of new chemicals introduced each year and found in products we use everyday.
  • 53: the average number of cancer causing (carcinogenic) chemicals we each have in our bodies.

Internal factors leading to genomic instability include errors in DNA replication and oxidative stress.

As we age we lose capacity to repair damaged DNA. This in turns leads to further DNA instability leading to more mutations and an increasing downward spiral leading to disease and eventually death.

Telomere Attrition

Telomeres affect how cells age and are essential for maintaining cell integrity. We have a half dozen or so articles on this website on telomeres.

Telomeres are small protective caps at the end of our chromosomes similar to the aglets at the end of our shoelaces. Each time a cell divides the telomeres get shorter. In utero, our telomeres are about 15,000 base pairs long. Bu the time we are born we are down to 10,000 base pairs. Telomeres are about 4,000 base pairs in the elderly.

The shorter telomeres get, the less protection they provide the chromosomes. Eventually, a cell loses its ability to divide and either goes under cell death or apoptosis, or continues to live but is non-functional which is called cellular senescence (the 7th hallmark). Apoptosis is preferred over cellular senescence. Cellular senescence can lead to other problems at the cellular level.

Oxidative stress, inflammation, toxins, stress and more causes cells to divide more to repair damage. This leads to more rapid telomere shortening.

Smoking accelerates telomere shortening. A person who smokes a pack a day for 40 years sees telomere shortening equivalent to 7.4 years of life.  Obesity is even more harmful to our telomeres causing telomere shortening equivalent to 8.8 years of life.  Daily stress is the worst.  Telomere shortening in stressed women was equivalent to 10 years of life.

Epigenetic Alterations

Epigenetic alterations refers to changes that regulate gene expression. Genes are turned off or on. Epigenetic alterations do not change the DNA sequence but trigger alterations that determine whether a gene is turned on or off. You may have genes that predispose you to a particular disease, but those genes need to be turned on in order to lead to that particular disease. Your lifestyle goes a long way in determining if a given gene is turned on or off.

Diet, lifestyle choices, stress, and the environment can influence the expression of a gene. Is the gene on or is it off?  Epigenetic alterations become more pronounced as we age which can lead to progression of cancer, diabetes, neurodegenerative diseases, and osteoporosis.

Loss of Proteostasis

The body strives for a state of homeostasis or balance – not too much of one thing or too little of another. This balance includes a balance of protein synthesis, protein folding, and protein degradation to prevent accumulation of damaged or misfiled proteins. Such accumulation of damage protein leads to cellular dysfunction.

The ability to maintain proteostasis wanes as we age leading to accumulation of damaged and misfiled proteins contributing to aging and disease.

A hallmark of neurodegenerative disease like Alzheimer’s is the accumulation of aggregated proteins that lead to cellular dysfunction and ultimately cell death

Deregulated Nutrient Sensing

Deregulated nutrient sensing refers to the decline in the cell’s ability to determine or sense what nutrients are available. These nutrient sensing pathways play key roles in regulating cellular metabolism, energy balance, and growth. The insulin/IGF-1 was the first pathway demonstrated to regulate aging.

Mitochondrial Dysfunction

The mitochondria are the power plants in the cells. Cells can have hundreds to thousands of mitochondria. The mitochondria produce energy in the form of adensoine 5′-triphosphate commonly known as ATP.

Dysfunction in the mitochondria leads to increase in reactive oxidative species that fuel inflammation. Mitochondrial dysfunction is associated with cancer, heart disease, and metabolic diseases like diabetes.

Cellular Senescense

Cellular senescence occurs when a cell can no longer divide but remains metabolically active. This is called a zombie state. Senescent cells cause more harm than good. As we stated under “telomere attrition” it is better that a cell die (apoptosis) where cell parts can be recycled than live in a zombie state. The accumulation of senescent cells triggers chronic inflammation leading to age-related diseases.

Senescent cells also secrete substances that turn neighboring healthy cells senescent as well.

Stem Cell Exhaustion

Stem cells have the ability to differentiate into other types of cells or tissues and are the key to replenishing dying cells. Stem cells enable regeneration of tissues to occur. Two things happen to stem cells as we ago. One, there are fewer stems. Two, the stem cells that exist are not as robust as we age compared to when we were younger. Thus, stem cell function declines with aging thus increasing the chances of neurodegenerative diseases, cardiovascular diseases, and cancer.

Altered Intercellular Communication

Cells in the body communicate with one another through a variety of means. Altered communication occurs with aging as the signals between cells is either lost, misinterpreted, or ignored – not unlike human communication. This miscommunication interrupts normal cell function predisposing to disease and aging.

Chronic Inflammation

Chronic inflammation is one of the three new hallmarks of aging, but its presence and significance has been known for several years. We have three posts dedicated to chronic or silent inflammation: Silent Inflammation and Chronic Disease, How to Treat Silent Inflammation, How Do I Know If I Have Silent Inflammation?

Chronic or silent inflammation is constant, lingering, and low grade inflammation that taxes cellular function and repair. In addition, there are pro-inflammatory pathways that contribute to aging and exacerbation chronic disease related to aging. Read How to Treat Silent Inflammation to develop some known strategies to keep this hallmark of aging at rest.

Disabled Macroautophagy

Autophagy is the body’s process by which it gets rid of damaged or dysfunctional cell organelles and proteins (see loss of proteostasis). Autophagy is a necessary process but is hindered by age, oxidative stress, mitochondrial dysfunction, and epigenetic factors. You can think of autophagy as an inner healing process. Disabled autophagy is linked to Alzheimer’s disease, type 2 diabetes, and cardiovascular disease.


The gut micobiome has been referred to the body’s second brain. The microbiome consists of all the micro-organisms that live in our gut. Believe it or not, but there are more micro-organisms in the human gut than cells in the human body. It is estimated that there are 100 trillion micro-organisms in the gut.

They must be there for a reason. These micro-organisms play a key role in numerous physiologic activities critical to human health. Our body is in a symbiotic related with many of these organisms. A disruption in the normal micro-orgnisms in the gut (the normal flora) can lead to infection, obesity, diabetes, allergies, neurologic disorders, and inflammatory bowel disease.

In the Gut Microbiome: How to Keep it Healthy we discuss the significance of the gut microbiome in more detail and provide strategies to keep it healthy.

Many of these hallmarks of aging are interrelated. So when you minimize the harm of one you are likely minimizing the effects of some of the other hallmarks. How you eat and whether or not you exercise will enable you to live longer younger. See our article Exercise and Nutrition in a Nutshell. 

It is likely that scientists in the not so distant future will develop strategies to slow or reverse aging,


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Dr. Joe Jacko

Dr. Joe is board certified in internal medicine and sports medicine with additional training in hormone replacement therapy and regenerative medicine. He has trained or practiced at leading institutions including the Hughston Clinic, Cooper Clinic, Steadman-Hawkins Clinic of the Carolinas, and Cenegenics. He currently practices in Columbus, Ohio at Grandview Primary Care. Read more about Dr. Joe Jacko

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