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As we age, cells show an increase in self-preserving signals that result in damage elsewhere in the body. Altered intercellular communication contributes to symptoms and diseases that are associated with declining health.

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Today, we conclude our nine-part series on the Hallmarks of Aging. If you have followed along, you will find that each hallmark either directly or indirectly affects the other. (Start here if you’d like to start with the first hallmark.)

The first four hallmarks are considered primary since they are believed to be actual causes of aging and have a definitive negative effect on DNA. They are what first initiate cellular damage, which then leads to accumulation and progressive loss of function. They are:

·  Genomic instability

·  Telomere attrition

·  Epigenetic alterations

·  Loss of proteostasis

The next three are called antagonistic, as they ultimately respond to the damage caused by the primary hallmarks. However, they are initially designed to have protective factors. It is only when bodily conditions become chronic and/or aggravated that they contribute to cellular damage. They are:

·  Deregulated nutrient-sensing

·  Mitochondrial dysfunction

·  Cellular senescence

The last two hallmarks are thought to be integrative because they “directly affect tissue homeostasis and function.” These come into play once the accumulated damage caused by the primary and antagonistic hallmarks can no longer be stabilized. Once this happens, the functional decline is inevitable. They are:

·  Stem cell exhaustion

·  Altered intercellular communication

This week, we will cover the final hallmark: altered intercellular communication. The primary and antagonistic hallmarks each contribute to the variety of breakdowns in communication within and around our cells, thus the reason for altered intercellular communication is identified as one of the two integrative hallmarks.

Communication is everything

Our cells process millions of signals every day. Scientists have spent entire careers discovering how different signals and intercellular pathways work. It’s that important. When communication gets disrupted, it can allow disease to set in, such as cancer cells growing out of control. In fact, most diseases involve at least one breakdown in cell communication.

How a cell gives and receives messages with its environment and with itself is critical to its survival. It processes information from the outside, such as changes in temperature, variation in light levels, and availability of nutrients. It also communicates with other cells via chemical and mechanical signals, which cause alterations in their function.

Protein receptors embedded in the cell membrane connect membrane signals that affect the inner chemistry of the cell. This allows the direct passage of molecules between the internal and external compartments of the cell. All of this translates into how our cells adapt and change based on our environment and what our bodies need. This includes functions from gene expression and glucose regulation to our overall development.

Inflammation and aging don’t mix

As we age, the signals that send chemical messages across our bodies tend to become more inflammatory. This inhibits our immune system and can cause muscle wasting, bone loss, and other detrimental effects. This gradual increase of systemic inflammation in the body as we age is called inflammaging.

This consistent growth in inflammation leads to cells increasingly activating a chemical in their nuclei that regulate inflammation. This protein complex, called NF-kB, is involved in responses to heavy metals, free radicals, bacterial and viral antigens, and even stress. When it is over-produced, it leads to damaging consequences and becomes a significant risk factor as we age.

Cellular senescence, one of the antagonistic hallmarks of aging, is one of the main factors contributing to inflammaging. Senescent cells are known to negatively affect neighboring cells because they release pro-inflammatory cytokines, growth factors, and proteases that affect the function of nearby cells and incite local inflammation. This is a concept known as the bystander effect.

Inflammaging also hinders our immune system’s ability to effectively clear pathogens and dysfunctional cells, such as those that turn into cancer. This is known as immunosenescence. 

And as inflammatory reactions accumulate, neurohormonal signaling also becomes deregulated as we age. When NF-kB is activated in the hypothalamus, it has been shown to inhibit the production of gonadotropin-releasing hormone (GnRH). The reduction of this hormone can lead to skin degradation, muscle weakness, and bone fragility. It can also affect food intake and metabolism.

How to improve intercellular communication

Dietary/caloric restriction, mentioned in many of our blogs in this series, is one of the most studied ways to potentially restore, or at least improve communication between our cells as we age. As recently as February 2020, scientists in the US and China collaborated to study the cellular effects of a calorie-restricted diet.

“The primary discovery in the current study is that the increase in the inflammatory response during aging could be systematically repressed by caloric restriction,” says co-corresponding author Jing Qu, also a professor at the Chinese Academy of Sciences.

Including more foods that are known to reduce inflammation, such as green leafy vegetables, fatty fish, berries, and olive oil can help to reduce the effects that inflammaging has on our bodies as we age. “A healthy diet is beneficial not only for reducing the risk of chronic diseases, but also for improving mood and overall quality of life,” Dr. Frank Hu, professor of nutrition and epidemiology in the Department of Nutrition at the Harvard School of Public Health, says.

Additionally, since the gut microbiome is an integral part of our immune system, it appears possible to extend healthy aging and lifespan by focusing on the health of our intestinal bacterial ecosystem.

What else can I do?

My best-selling book, The Longevity Equation, provides a step-by-step blueprint to hack your genes, optimize your health and master the art of existence. In my book, I take an in-depth look at aging, explore what it means to extend your healthspan, and outline the pathways and factors that lead to a lifelong solution to the burdens of aging.

In collaboration with TruDiagnostic™, I have developed The Longevity Equation Epigenetic Consult. We are offering a revolutionary new way to access your health using an epigenetic test called TruAge™. This test will help tell you what your body is actually doing right now and what that means. 

TruAge™ works by using mathematical models and a powerful algorithm to measure DNA methylation-based biomarkers. Methylation is what modifies the function of the genes in the body by adding what’s called a methyl group to DNA, which is what signals genes to turn on or off. DNA methylation is the best indicator of age-related changes and is the best-studied biomarker of age. This comprehensive testing method determines your epigenetic, or biological age, and can detect the acceleration of aging before the signs of aging even begin to appear.

The Longevity Equation Epigenetic Consult is intended to give you a snapshot of your biological age, as well as the lifestyle and environmental shifts you can make right away to start adding vitality and wellness into your life. Click here to schedule your consult!

More about The Institute for Human Optimization

The Institute for Human Optimization is committed to helping you create a personalized plan for living your longest, healthiest life possible. My team and I leverage the most cutting-edge advances in genetic testing, nutritional analysis, and functional medicine to get to the root biological imbalances that cause aging.

The Institute for Human Optimization was created with the intention of pursuing a highly personalized approach to longevity medicine to help enhance healthspan. Where lifespan is the actual number of years we’re alive, healthspan is how many of those years are spent in health and wellness.

We believe that a long healthspan – not just a long lifespan – is the most important thing you can cultivate. A long healthspan means you don’t miss out on life as you get older. It means remaining independent and having the vitality to travel and see the world.  A long healthspan means that you can be there – in full body and mind – for the people who need you the most and that every day will feel like a gift.

We know that each person is truly unique. From DNA to iris, we all possess a blueprint that is genetically inherited and environmentally influenced. By gaining a deeper appreciation for the person on a molecular level and addressing the root causes driving disease, we can help promote optimized health through our unique scientific, N of 1, approach to individualized care.

The Institute for Human Optimization provides the most comprehensive, data-driven, personalized approach to wellness. It is:

·   Predictive – We use genomics and advanced biomarker testing to risk stratification and empowerment.

·   Personalized – We use data-driven health information to curate actionable change for disease mitigation and prevention.

·   Preventive – We utilize highly individualized programs tailored to your unique genomic blueprint.

·   Participatory – We empower engagement in personal choices, which allows for improved outcomes and enhanced results.I am so excited about the possibility to support you on this cutting-edge journey to extend your lifespan AND your healthspan. Click here to schedule Your Longevity Equation Epigenetic Consult! Can’t wait to meet you!
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Our bodies have a built-in process that is believed to be a protective mechanism called cellular senescence. As we age, this process slows down and can result in disease.

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The biological definition of aging is the many processes of cellular damage accumulation in the body. These are known in the scientific literature as the Nine Hallmarks of Aging. We’ve covered the first four, or primary, hallmarks: genomic instability, telomere attrition, epigenetic alterations, and loss of proteostasis, as well as the first two of the antagonistic: deregulated nutrient-sensing, and mitochondrial dysfunction.

The role of the antagonistic hallmarks is to respond to and block the damage caused by the primary hallmarks. Yet, when bodily conditions become chronic and/or aggravated, they end up contributing to cellular damage and can accelerate aging. The seventh hallmark, and third of the antagonistic, is cellular senescence. Senescence plays roles in normal development, maintains tissue homeostasis, and limits tumor progression. If you’ve read any of my blogs in the past, you know this is one of my favorite topics.

The miracle that is us

It varies depending on the cell, but the division cycle of a typical human cell averages 24 hours, which is mind-blowing considering the complexity of what takes place.

Figure 1: The cell cycle Courtesy: National Human Genome Research Institute

Our cell cycle has four stages:

·         G1 (gap 1) stage: where the cell prepares to divide. This is the longest phase, where the cell is metabolically active and continues to grow, but does not replicate its DNA.

·         S (synthesis) stage: where the cell copies its entire DNA.

·         G2 (gap 2) stage: where cell growth continues and it organizes and condenses the genetic material and prepares to divide.

·         M (mitosis) stage: where the cell separates the two copies of chromosomes into two daughter cells. This is the most dramatic stage, ending in the cell division in a process called cytokinesis.

 A fine line between helping and hurting

In my best-selling book, The Longevity Equation, I point out that, “When your cells have had more than enough DNA damage, stress, and telomere shortening, they enter a state of growth arrest known as cellular senescence. This function is put in place to prevent damaged cells from turning into cancerous cells. However, in the process, it also stops allowing worn-out tissue to be replenished and rebuilt. Senescent cells often secrete inflammatory molecules that further damage the cellular environment, leading to chronic inflammatory conditions, including heart disease and osteoarthritis.”

Cellular senescence inevitably halts the cell cycle during the G2 stage, as a result of excessive intracellular or extracellular stress or damage, such as oxidative stress, DNA damage, and telomere erosion, or when they overexpress certain oncogenes (have the potential to transform into a tumor cell). Once this process starts, it is irreversible.

Similar to the other antagonistic hallmarks of aging, this process is meant to prevent the proliferation of damaged cells and helps to suppress malignant cell formation. However, as time goes by, our bodies begin to accumulate these senescent cells, which leads to the deterioration of the tissue repair mechanism that usually accompanies senescence.

Crossing the threshold

When a cell enters senescence and it stops producing copies of itself, it excretes hundreds of proteins, which in moderation in healthy tissue, signal the immune system to initiate cellular housekeeping, called autophagy, and start the repair process.

However, when disease and aging cause extensive damage in the tissues, senescent cells build up and stay in a state of suspended animation – not alive, but not quite dead. Some scientists call these twilight cells, and others go for a more Hollywood description of zombie cells because they can negatively affect surrounding cells if not cleared efficiently by the immune system.

Again, from my book, The Longevity Equation, “Unlike other damaged cells, zombie cells don’t self-destruct or clear out of the way to make room for healthy cells. Instead, they stick around and interfere with the body’s natural rebuilding and replenishing mechanisms. . .”

Senescent cells cross the threshold from being protective to deleterious when their accumulation causes them to excrete an overabundance of molecules like pro-inflammatory cytokines, growth factors, and proteases that affect the function of nearby cells and incite local inflammation.

Can we clean up the excess?

While there is no magic bullet and research is still learning how to extend our lifespan and our healthspan, studies on cellular senescence are very promising and it seems as though therapies are on the horizon.

That getting rid of senescent cells is enough to effectively rejuvenate an animal—that tells you they’re a really important driver of aging,” says Lorna Harries, a molecular geneticist at the University of Exeter in the UK who studies cell senescence.

In the meantime, I have developed a potent blend of phytonutrients that can help stimulate autophagy and dramatically enhance the number of senescent cells that your body can eliminate. It’s the only supplement of its kind that works on a cellular level to help flush toxic senescent cells out of your body and pave the way for fresh, new, rejuvenating cells to take their place.

It’s called Restori-Cell, and it gives you a way to rewrite the script and change the way you think about aging. It boosts mental clarity, promotes youthful, all-day energy and supports a natural, healthy weight. Restori-Cell meets the highest standards of quality and features five highly specialized nutrients in scientifically supported doses:

What else can I do?

The Longevity Equation provides a step-by-step blueprint to hack your genes, optimize your health and master the art of existence. In my book, I take an in-depth look at aging, explore what it means to extend your healthspan, and outline the pathways and factors that lead to a lifelong solution to the burdens of aging.

In collaboration with TruDiagnostic™, I have developed The Longevity Equation Epigenetic Consult. We are offering a revolutionary new way to access your health using an epigenetic test called TruAge™. This test will help tell you what your body is actually doing right now and what that means. 

TruAge™ works by using mathematical models and a powerful algorithm to measure DNA methylation-based biomarkers. Methylation is what modifies the function of the genes in the body by adding what’s called a methyl group to DNA, which is what signals genes to turn on or off. DNA methylation is the best indicator of age-related changes and is the best-studied biomarker of age. This comprehensive testing method determines your epigenetic, or biological age, and can detect the acceleration of aging before the signs of aging even begin to appear.

The Longevity Equation Epigenetic Consult is intended to give you a snapshot of your biological age, as well as the lifestyle and environmental shifts you can make right away to start adding vitality and wellness into your life. Click here to schedule your consult!

More about The Institute for Human Optimization

The Institute for Human Optimization is committed to helping you create a personalized plan for living your longest, healthiest life possible. My team and I leverage the most cutting-edge advances in genetic testing, nutritional analysis, and functional medicine to get to the root biological imbalances that cause aging.

The Institute for Human Optimization was created with the intention of pursuing a highly personalized approach to longevity medicine to help enhance healthspan. Where lifespan is the actual number of years we’re alive, healthspan is how many of those years are spent in health and wellness.

We believe that a long healthspan – not just a long lifespan – is the most important thing you can cultivate. A long healthspan means you don’t miss out on life as you get older. It means remaining independent and having the vitality to travel and see the world.  A long healthspan means that you can be there – in full body and mind – for the people who need you the most and that every day will feel like a gift.

We know that each person is truly unique. From DNA to iris, we all possess a blueprint that is genetically inherited and environmentally influenced. By gaining a deeper appreciation for the person on a molecular level and addressing the root causes driving disease, we can help promote optimized health through our unique scientific, N of 1, approach to individualized care.

The Institute for Human Optimization provides the most comprehensive, data-driven, personalized approach to wellness. It is:

·   Predictive – We use genomics and advanced biomarker testing to risk stratification and empowerment.

·   Personalized – We use data-driven health information to curate actionable change for disease mitigation and prevention.

·   Preventive – We utilize highly individualized programs tailored to your unique genomic blueprint.

·   Participatory – We empower engagement in personal choices, which allows for improved outcomes and enhanced results.

I am so excited about the possibility to support you on this cutting-edge journey to extend your lifespan AND your healthspan. Click here to schedule Your Longevity Equation Epigenetic Consult! Can’t wait to meet you!

On the Institute for Human Optimization blog this week, we discuss the hallmarks of aging as described in the groundbreaking paper published by Carlos Lopez-Otin in 2013. It is important to understand that though these are normal changes the body goes through as it ages, we can take active steps to increase our health spans and allow these processes to happen more slowly. Here, we layout the difference between your chronological age and biological age, the nine hallmarks of aging and, a new technology that changes the way we look at the aging process.


How old are you, anyway?

Your age is not just the number of days, months, and years you’ve existed. There are two ways to think about your age: chronologically and biologically.

Your chronological age is an easy-to-determine figure as it is based on the number of years that have passed since you were born. It is characterized by age-related milestones and benchmarks that are celebrated with the passage of time. Your biological age, also referred to as phenotypic age, on the other hand, is based on lifestyle, genetics, physical and mental functions among many other factors. It is influenced by signals, inputs, and information that your body has been exposed to throughout your life.

Lifestyle factors such as poor nutrition, alcoholism, smoking, inactivity, insomnia, and stress to name a few can increase your biological age, influencing your genes and causing the effects of aging to happen faster.  Depending on your lifestyle and genetics your biological age can be much higher (or lower) than your chronological age.

While chronological aging is inevitable, biological aging is manageable and even reversible. It is also possible to be a 50-year-old person with a younger biological age due to a more active, healthy lifestyle. In contrast, it’s also possible to be a 50-year-old person with a younger biological age due to a more active, healthy lifestyle. This was most recently demonstrated in Dr. Gregory Fahey’s research publication that demonstrated a Reversal of epigenetic aging and immunosenescent trends in humans published in Aging Cell in September of 2019.

There are nine hallmarks of aging.

Throughout my medical career, I’ve been fascinated by the aging mechanisms of the human body. I believe understanding the hallmarks of aging can give us an insight into what is going on inside our bodies and how we can apply that knowledge to make educated decisions about our health.

There are nine hallmarks of aging which are completely natural and will happen to all of us eventually. They are:

Genetic Instability

Damage to your DNA is happening all the time (at a rate of 10,000 to 100,000 molecular lesions per day!). Thankfully, your body has systems in place for repairing the strands and making sure your body doesn’t break down completely.

As we age, however, the repair systems become less efficient at their job which results in creating tiny chromosomal errors that add up and can eventually lead to disease. Though this happens naturally, DNA repair systems can be negatively affected by lifestyle factors such as heavy alcohol consumption or poor sleep.

Some researchers, such as David Sinclair, have been working with molecular substances such as NAD and its precursor NMN, which may help your DNA repairers stay working for longer.

Telomere Attrition

Telomeres are little caps on the end of your chromosomes that protect your genetic data. Each time your cells divide, these telomeres get a little shorter until they wear away completely, causing genetic instability. Measuring your telomeres is how we can determine your biological age.

Many researchers have been concentrating on ways to improve telomere health, which in turn can extend people’s lifespans. RNA therapy is one method that is being discussed, though it’s still in the preliminary stages.

Epigenetic Alteration

If your genes are a CD, your epigenome is the laser that reads the information and plays the song. It has the power to turn genes on or off and controls protein production in certain cells.

As you age, environmental factors can modify your epigenome slowly, making it less effective at reading your DNA- like “skipping” on a CD. The good news is that these changes to the epigenome are not permanent so hypothetically, researchers could find a way to reverse the damage and this particular hallmark of aging.

Loss of Proteostasis

This is a decline in the quality of the proteins that keep our cells doing what they do. After decades of toxins from the environment and our food assaulting our cells, they become damaged. 

Your body has a natural defense against these damaged cells called autophagy. Autophagy is essentially the body’s housekeeping program, cleaning out the old dead cells so they don’t cause problems. But over time, the housekeeper becomes less effective, resulting in a build up of “zombie cells” that can produce age-related diseases like Alzheimers and Parkinson’s.

One way to accelerate autophagy and keep that housekeeper busy is by intermittent fasting- that is, going 16 or more hours a day without consuming calories. 

Deregulated Nutrient-Sensing

Your body has a built-in nutrient-sensing system that its only job is to make sure you’re eating enough healthy, nutritious foods. As you age, even these systems start to break down and have a hard time determining what you need.

Years of eating processed, unnatural foods put added stress on these nutrient sensors and cause us to age faster. Our hypothalamus can be affected, causing us to be hungrier than normal and eat too many calories, which further degrades the nutrient-sensing systems. 

Calorie restriction remains one of the leading age interventions related to these systems, keeping them working and determining correctly when you’ve had enough vitamin D or need a little more C.

Mitochondrial Dysfunction

Mitochondria are commonly called the “powerhouse” of the cell. It’s where they generate the energy to carry on with their job of keeping you going. Free radical damage over time degrades the mitochondria and less energy is produced, making your cells slower and more lethargic.

This decline is most often seen first in tissues with high energy demand: the brain and heart. This is one of the reasons our mental faculties decline as we get older. This hallmark has become a major focus of anti-aging research; If we can keep our cells powered, they can keep doing their jobs for longer and keep us healthier in the process.

Cellular Senescence

To keep your body refreshed and young, your cells have to constantly divide. This is why little kids grow so fast as their cells divide at a rapid rate during developmental years and then slow down as they become adults.

The truth is, your entire body is replaced with a completely new set of cells every 7-10 years, and more important organs are replaced even faster than that. There is an inner mechanism though, that acts like a biological clock; Your cells can only divide a certain number of times.

When a cell can no longer split itself into more cells, it is called cellular senescence. Through autophagy, the body cleans these dead cells out but as we get older, our bodies stop doing this as efficiently. The senescent cells pile up, causing inflammation and a host of problems.

Researchers have been diving into the world of senolytics, a fascinating set of compounds that were found to improve autophagy in mice, making them look and act younger. Perhaps one day we can use similar substances to mimic the effect in humans.

Stem Cell Exhaustion

Stem cells are the blank slates from which all cells are created. All the other hallmarks of aging as well as environmental factors eventually lead to stem cell exhaustion. This is when the body is unable to replace stem cells that have migrated, differentiated, or died. Fewer stem cells mean less regeneration, meaning we start to show signs of getting old.

Anti-aging scientists are obsessed with rejuvenating these stem cells through various means, hoping to increase the number of stem cells in the body and keep you rejuvenated well into your golden years.

Altered Extracellular Communication

Cells need to talk to each other to make everything work properly. How well would a factory operate if no one knew what was going on with everyone else? As we age our cells start to have problems communicating with each other- this can lead them to make bad decisions about regulating our hormones, hunger signals and sleep cycles.

Keeping cells healthy and well-nourished can keep them communicating longer, which in turn will keep your body running smoothly.


These nine hallmarks of aging will be an overarching theme for the future of this blog. Since the publication of the Lopez-Otin’s report, anti-aging scientists have been able to make amazing progress towards not only increasing our chronological age but our health spans as well.

We hope to continue to educate people about what happens to our body systems as we age and provide well-researched ways to postpone these hallmarks as long as possible.

How can you find out your biological age?

Until recently, there was no way to measure a person’s biological age. We are proud to be in collaboration with TruDiagnostics, a company on the cutting edge of anti-aging research. With this new test, we can look at almost 900,000 spots on the genome, which is 425 times more data than any other test on the market! By measuring these factors, we can determine your biological age and see if our anti-aging interventions are truly making a difference.

The Institute for Human Optimization will be offering this test to patients in an attempt to inform them about what’s going on at a cellular level and base our recommendations on this personalized data. 

ReferenceLópez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013; 153(60):1194–1217. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174/