A blueprint of a genetic “you”.

Our DNA determines an overwhelming amount of information about who we are, but other factors can also influence our health expression. Over the past few decades, the science and technology, and their applications in genomic have made breakthrough progress. Genomic data and genomic medicine services have become relevant in clinical applications as more and more clinicians use genomic data with the diagnosis and treatment of patients. How is genomics being used in medicine?

Let’s first start with answering: What is a Genomics?

In last week’s blog, we briefly discussed the Human Genome Project – a research project that successfully sequenced for the first time the entire human genome. This landmark effort was a breakthrough biomedical discovery in Genomics. Genomics is the study of your Genome, which is all your genes, including how your genes interact with each other and with your environment.

This is an exciting field in medicine as clinicians and researchers can analyze a genomics approach to understand the mechanisms of disease and work towards a preventative approach.

Clinical Application Difference between Genomics vs Genetics

Genomics refers to the study of your global genomic blueprint and how it orchestrates dynamic biochemical processes which influence your current state of health.

Genetics refers to a specific division of genomic medicine that focuses on rare disease findings associated with specific inherited gene mutations, inborn errors of metabolism.

The Institute for Human Optimization not focusing on the rare and obscure but translating your global genomic blueprint to self-decode and translate this information into actionable outcomes to harness your health potential.

Genomics in Medicine Today

Genomics allows providers to practice in a proactive care delivery mode. Modern genomics is being used in the following:

  • Prenatal Genetic Screening Tests
  • Cancer Research
  • Polygenic Risk Scores
  • Preimplantation diagnosis
  • Companion diagnostics for prescribed drugs
  • Epigenetics and gene regulation
  • Next-generation sequencing
  • Looking at the patient’s exome

Prenatal Genetic Screening Tests: Widely used currently, clinicians use genomic data during first and second trimester Prenatal Genetic Screening Tests which looks at a very small amount of fetal DNA (done by a simple blood draw) which looks at whether the fetus has certain genetic disorders such as Sickle Cell Disease, Cystic Fibrosis, and more.

Cancer Research: Genome sequencing in Cancer is a clinical area where genomics is being heavily researched. By using genomic data, researched have a better understanding of the biology of cancer and are leveraging this to find new ways to treat the disease.  Additionally, utilizing genomic data is a promising step to predict cancer risk, prognosis, and precise response to treatment.  

Polygenic Risk Scores: Additionally, a potential clinical service tool is looking at Polygenic Risk Scores. Polygenic risk scores look at your polygenic genetic architecture to identify genetic variants associated with diseases. With an increasing amount of research correlating Polygenic risk scores with disease status, this information can be useful in clinical decisions with individuals at high genetic risk of disease for risk stratification

Preimplantation Genetic Diagnosis: In Preimplantation Genetic Diagnosis, whole-genome sequencing of embryos prior to implantation is performed for pathogenic variation screening. This is used to prevent the transmission of known genetic diseases.

Companion Diagnostics for Prescribed Drugs: Companion diagnostics are medical devices that are used by clinicians to aid them in deciding which treatments and dosage to give specifically to that individual patient utilizing genomic insights. This medical device can be an in vitro diagnostic or an imagining tool that provides information needed to find a personalized treatment option by identifying what FDA-approved treatment options would be best suited for their individual case.

Epigenetics and Gene Regulation: the National Institute of Environmental Health Sciences defines Epigenetics as ‘a rapidly growing area of science that focuses on the processes that help direct when individual genes are turned on or off.’ Epigenetic regulation of gene expression is at the forefront of modern Genomics currently being used to assess your Biological age.

Next Generation Sequencing (NGS): refers to a method used to sequence DNA. This method is currently used by Pediatricians for Genomic diagnosis of Pediatric disorders. It is also being used by Oncologists for Precision Oncology migrating cancer treatments to a precision medicine approach.

Exome Sequencing: also known as whole-exome sequencing looks at expressed genes to try to find a genetic cause for disease expression. This is a genomic technique that is clinically relevant as most genetic variants in genetic diseases are expressed in the exome.

The Future is a Precision Medicine Approach

Already, more and more individuals have taken the first steps to obtaining information about their genome by using Direct-to-Consumer DNA testing services. More and more, people want to know more about their genome, whether that means information about ancestry, or a more medically information trait of disease, this has sparked consumer interest in personalized information about our health, genealogy, and more.

We have the blueprints to a genetic “you” and scientists have figured out what each specific gene does itself when changed or removed but now understanding how all genes work together in synchrony, and most importantly how to best use genomic information to improve clinical care is still being established.

Despite these challenges, at the Institute for Human Optimization, we are currently utilizing advanced molecular testing to predict how genes are theoretically behaving by assessing their structural makeup and biochemical expressions.

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!

The advent of high-throughput technologies in the field of genomic sciences and systems biology has brought about a revolution in primary prevention.  From the early era of sequencing when short genomic reads were being characterized to the current era where the idea of personalized genomes has become a possibility, science has progressed tremendously. Omics refers to the review of specific types of medical information on a complete and comprehensive spectrum that ends in the suffix – omics. Omics-based medicine and systems biology will realize a new approach to practicing medicine – personalized, predictive, and precise medicine.

.  .  .

Human Genome Project- The beginning of a new era of personalized medicine

The Human Genome Project (HGP) was the first step toward personalized medicine when it completed the sequencing of the first complete human genome. Whole-genome sequencing refers to the entire genome (your complete set of DNA, or deoxyribonucleic acid) being sequenced. The HGP was led by an international team of researchers leading a scientific research effort to determine what parts make up human DNA, and also of mapping and identifying all of the human genes of the human genome. Despite recent technologies driving down the cost, it is still been expensive making it unfeasible for most to conduct individual genome sequencing. Recent advancements in technology resulted in a marked reduction in the cost thereby enabling personalized Whole Genome Sequencing (WGS) which allows for the characterization of disease on a molecular level.

An even more promising alternative to the WGS is the whole-exome sequencing (WES) which permits the study of only the exonic or functional regions of the genome. This means instead of sequencing your complete set of DNA, you are only sequencing the protein-coding regions of genes in a genome. This technology is a fraction of the cost of WGS. WGS is a promising and cost-effective step towards the development of therapy tailored to individual needs.

Going beyond the genome: Exploring the other omics

Source: https://err.ersjournals.com/

Transcriptomics

Transcriptomics is the study of the transcriptome, or the entire RNA transcripts including the mRNA, non-coding RNA, and small RNAs, produced by the genome. The goal of transcriptomics is to detect which genes are expressed in the given sample. By collecting and comparing transcriptomes of different types of cells, clinicians can gain a deeper understanding of what makes a specific cell type, how that type of cell conventionally functions, and how changes in the regular level of gene activity contribute to disease.

Proteomics

Proteomics is the study of proteomes. A proteome is the entire set of proteins that are produced or modified by an organism. Proteomics provides important insights into our understanding of cell signaling, a key aspect of biological life. Cell signaling allows cells to perceive and respond to the extracellular environment allowing development, growth, immunity, and more!

The growth of proteomics has helped in providing insights on the data missing from transcriptome analysis. Proteome research is currently being used in the characterization of diseases like cancers, studying the effects of post-translational modification (chemical modifications that play a key role in functional proteomic), and biomarker discovery. Proteomic technology is extremely complex but new proteomics tools have enabled researchers to dive deeply into signaling networks, allowing them to find out information on interactions among key molecules.

Metabolomics

Metabolomics is the study of small molecules, commonly known as metabolites, within cells, biofluids, tissues, or organisms, produced as a consequence of the metabolic processes. These small molecules constitute the metabolome and their study provides insight into various biological pathways involved in common disorders. Further advancements in metabolomics will aid in disease risk assessment, diagnosis, and therapeutics. Profiling of individual metabolites can be very beneficial for biomarker discovery which in turn is useful for the early diagnosis of the diseases and for personalized therapeutic strategies.

Epigenomics

Epigenomics is the study of the complete set of epigenetic modifications on the genetic material of a cell, known as the epigenome. The epigenome consists of a multitude of chemical compounds that can tell the genome what to do. The genome is passed from parents to their children and from cells, when they divide, to their next generation. Much of the epigenome is reset when parents pass their genomes to their children; however, sometimes, can be inherited from generation to generation. Interestingly, lifestyle and environmental factors (such as lifestyle, diet, and disease) can expose a person to pressures that prompt chemical responses which result in changes to the epigenome throughout a person’s life. Epigenomics is a fascinating field as it is vital to better understand the human body and to improve human health. Emerging epigenomic map technology will facilitate better prevention, diagnosis, and treatment of disease.

Microbiomics

Microbiomics is the study of microbial cells – including bacteria, fungi, protozoa, and viruses that collectively constitute the microbiome. The human microbiome is the aggregate of all microbiota in a human body. A large body of research has demonstrated a strong association between the gut microbiome and disease. Microbes ( a microorganism) have been associated with neurological disorders ranging from degenerative diseases (such as Alzheimer’s, Parkinson’s, ALS, and dementia) to mental health disorders (such as depression and anxiety) that are becoming, unfortunately, commonly diagnosed today. Microbiomics is a key component in personalized medicine as novel correlations between the human microbiome and health and disease are routinely emerging, furthering our quest for personalized medicine.

Pharmacogenomics

Pharmacogenomics assesses how individual genes affect drug interactions. It has been found that the same drug may produce variable effects on different individuals based on the differences in their genomic background. Genetic information could thereby assist in assigning drug doses to individuals based on their needs. It could also be very helpful in reducing the adverse effects associated with drugs.

Omics at a glance

Advantages

Omics testing is a very promising technology with a huge number of potential benefits. Capable of revolutionizing the healthcare and drastically improving health and lifestyle, this technology anticipates the development of personalized medicine.

In addition to its impact on patient care, it will also allow a deeper understanding of the disease pathogenesis, early diagnosis and intervention. Biomarker discovery is another potential advantage of Omics testing that will revolutionize diagnosis allowing us to delve deeper into disease risk factors and causes. Omics testing as a whole would be able to answer the problems arising from the complexity of the disease phenotype. Biomarker discovery is another potential advantage of omics testing providing useful signatures of disease. Pharmacogenomics will be relevant in clinical decisions about prescribing the best medication for you.

Future of Healthcare

Personalized Medicine has become the most modernized trend disrupting the healthcare industry in the most recent years. There has been a paradigm shift from ‘one-size -fits all” towards a precise and personalized approach.

The quest for personalized medicine has resulted in various advancements to achieve targeted care paths with a personalized multi-omics approach. With new technology, the interrelationships between the human genome, the microbiome, the metabolome, the proteome, the epigenome, the transcriptome, and other factors have shown to provide a better picture of our health journey, are just starting to be revealed. Researchers and clinicians have access to a new and thorough view of the molecular manifestation of diseases and with emerging technologies, can translate that into helpful advice that can be used in the prevention of diseases together with improved diagnostics and cure. In the future, Omics-data will utilize the patient’s individuality including their genetic make-up, lifestyle, and exposome which is defined as the “ totality of exposure individuals experience over their lives and how those exposures affect health. “ in decision making when it comes to disease management.

More about The Institute for Human Optimization

The Institute for Human Optimization we believe that Omics-based medicine and systems biology will realize a new approach to practicing medicine – personalize, predicative, and precise medicine. We are 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!

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.

.  .  .

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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Stem cells have exceptional abilities to self-renew and recreate functional tissues. When this regenerative potential begins to decline in our bodies, many researchers believe it is the defining moment when we begin to see age-related conditions manifest.

. . .

We have written about seven of the nine Hallmarks of Aging. The first four 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 cellular communication (more on this next week!)

This week, we will cover stem cell exhaustion. In one way or another, each primary and antagonistic hallmark of aging culminates in the diminished self-renewing capacity of stem cells, thus the reason it is identified as one of the two integrative hallmarks.

The marvel of stem cells

Your body comprises more than 200 cell types. Your liver cells are replaced every 300-500 days; your skin cells, every couple weeks; and your taste buds every 10 days or so. Your body continually manufactures new blood cells to replace old ones, and about 1 percent of the body’s blood cells must be replaced every day. White blood cells have the shortest life span, sometimes surviving just a few hours to a few days, while red blood cells can last up to 120 days or so.

Stem cells are the foundation for every organ and tissue in your body. While there are many types of stem cells, three are best known: embryonic, adult, and induced pluripotent.

Embryonic stem cells begin forming within five days after fertilization. They exist only in the earliest stages of development and are considered pluripotent, or undifferentiated, as they have the ability to give rise to every cell type in the fully formed body.

Adult stem cells, also known as somatic or tissue-specific stem cells, are multipotent, meaning they differentiate to yield the specialized cell types of the tissue or organ in which they reside, and may have defining morphological features and patterns of gene expression reflective of that tissue. These adult stem cells are responsible for repairing or replacing damaged tissue as we age or experience injury.

For therapeutic and research purposes, scientists are also able to generate induced pluripotent stem cells by re-introducing the signals that normally tell stem cells to stay as stem cells in the early embryo. These switch off any genes that tell the cell to be specialized, and switch on genes that tell the cell to be a stem cell.

Cells go through several stages while differentiating and become more specialized with each step. Signals secreted by other cells, physical contact with surrounding cells, and other molecules present in the body all contribute to the differentiation process.

Figure 1: An illustration showing different types of stem cell in the body. Image credit: Genome Research Limited

The effects of exhaustion

As we age, some of our adult stem cells repair and regenerate cells that have experienced wear and tear, injury or disease. They are not involved in normal tissue function, but remain quiescent – a state in which they do not divide, yet retain the ability to proliferate highly specialized cells specific to the organ and tissues where they reside. They are activated when the need arises. The unique ability of adult stem cells to maintain quiescence is crucial for life-long tissue homeostasis and regenerative capacity

The activation process of quiescent stem cells is very complex and requires precise reorganization to transition into a proliferative state, and it, unfortunately, declines over time. The consequences of stem cell exhaustion manifest in different ways, depending on the type of stem cell affected.

·  Hematopoietic (blood-forming) stem cell (HSC) exhaustion results in anemia and myelodysplastic syndromes, a group of blood disorders where stem cells do not mature into healthy blood cells.

·  Mesenchymal stem cells (MSCs) are found in bone marrow. They are important for making and repairing skeletal tissues, such as cartilage, bone and the fat found in bone marrow. When they become exhausted, osteoporosis can set in, as well as decreased fracture repair.

·  Myosatellite cells, or muscle stem cell exhaustion shows up as hindered repair of muscle fibers.

·  Intestinal epithelial stem cells (IESCs) are one of the most rapidly renewing cell populations in the body. When these become exhausted, one might accurately guess that intestinal function will be negatively impacted.

Help is on the horizon

It is estimated that the number of adults older than 65 will reach upwards of 88.5 million by 2050.  With this staggering number in the forefront, it is more important than ever to find therapeutic interventions to improve stem cell function.

As mentioned above, induced pluripotent stem cells are being avidly researched in order to more thoroughly understand the potential they could have on healing. While it is an absolutely promising and likely option to look forward to, it has not been perfected yet.

This brings us to the point, as it has in each blog of this hallmarks of aging series, where we look at what we can do in the meantime. The most promising and recent research illustrates the connection between a fasting-mimicking diet and the body’s ability to regenerate stem cells.

USC researchers found that a fasting-mimicking diet reduced intestinal inflammation and increased intestinal stem cells, in part by promoting the expansion of beneficial gut microbiota. The research team observed that the fasting component allowed the intestines to heal, but that the specific, calorie-restricted diet allowed the microbes in the gut to flourish, which was crucial to the stem cells rebuilding and regenerating.

Valter Longo, the director of the USC Longevity Institute at the USC Leonard Davis School of Gerontology and professor of biological sciences at the USC Dornsife College of Letters, Arts and Sciences says, “This study for the first time combines two worlds of research. . .The first is about what you should eat every day, and many studies point to a diet rich in vegetables, nuts and olive oil. The second is fasting and its effects on inflammation, regeneration and aging.”

What else can I do?

My bestselling 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!

Mitochondria serve as the powerhouses of our cells for which a delicate balance of energy flow is needed to generate energy production. Mitochondrial function has a substantial impact on the aging process and its dysfunction can accelerate aging.

. . .

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 of the antagonistic: deregulated nutrient-sensing.

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 sixth hallmark, and second of the antagonistic, is mitochondrial dysfunction. It is implicated in numerous age-related pathologies including neurodegenerative and cardiovascular disorders, diabetes, obesity and cancer.

Our source of cellular energy

You may remember from biology class that mitochondria are membrane-bound organelles, or specialized structures, within the cytoplasm our cells. Their main role is to metabolize, or break down carbohydrates and fatty acids, which creates energy-harvesting chemical reactions that result in adenosine triphosphate (ATP), often referred to as the energy currency of our cells. Mitochondria generate over 80% of our ATP through a process called cellular respiration, which requires oxygen. It does this via the oxidation of glucose.

Division, fusion and quality control

Mitochondria are highly dynamic and continually fuse and divide. Many cellular pathways allow this to happen, and these roles are critical, especially when cells encounter stress.

Mitochondrial fission, or division, is crucial to create new mitochondria for growing cells. Fission also contributes to quality control by enabling the removal of damaged mitochondria and can facilitate apoptosis (controlled cell death) during high levels of cellular stress. Mitochondrial fusion helps mitigate stress by mixing the contents of partially damaged mitochondria.

A 2017 research article in the journal, Genes, states that, “The maintenance of mitochondrial and cellular homeostasis requires a tight regulation and coordination between generation of new and removal of damaged mitochondria.”  When these mechanisms are disrupted, it affects normal development, which can lead to neurodegenerative diseases.

Mutations

Mitochondria contain their own DNA (called mtDNA), separate from the rest of the genes in the nucleus of our cells. It is for this reason that some researchers believe that mitochondria evolved from primitive bacteria that developed a symbiotic relationship with our cells over 1.45 billion years ago!

One of the causes of mitochondrial dysfunction is mutations in mtDNA, which occur mostly due to spontaneous errors during the replication process and damage repair. As we age, these mutations have been shown to increase in the human brain, heart, skeletal muscles and liver tissues.

Energy and oxygen

In electron transport chain, a cluster of proteins transfer electrons through a membrane within mitochondria, which releases energy that is used to form an electrochemical gradient that drives the creation of adenosine triphosphate (ATP). Without enough ATP, cells are not able to function properly, and, after a long enough period of time, may even die.

Unfortunately during the process, mitochondria also produce most of the free radicals, or as scientists like to call them: reactive oxygen species (ROS). Mitochondrial dysfunction is mediated by several processes including increased production of ROS. Until recently, some researchers believed that ROS were the main cause of aging. However, studies have shown that purposely lowering ROS did not have a negative effect on health and that in fact, increasing ROS could be helpful in signaling cellular stress. Regardless, the increased production of ROS can contribute to a loss of mitochondrial integrity and biogenesis.

SOURCE: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748716/, Licensee MDPI, Basel, Switzerland. 

Mitochondria are capable of self-replication, but progressively become more dysfunctional with age. They have built in quality control and housekeeping, but over time, these fail. As shown in the figure above from a research article in the journal, Genes, mitochondrial fusion and fission, a defective mitophagy process, and mitochondrial damage from increased mtDNA mutations, increased free radicals and oxidative damage and reduced ATP levels all contribute to age-related disorders associated with mitochondrial dysfunction.

How to improve mitochondrial function

While the jury is still out on exactly how to improve mitochondrial function and there is some controversy over some of the recommended treatments, there is agreement on a few ways to mediate mitochondrial dysfunction as we age.

A moderate level of eustress, or beneficial stress, has been shown to promote cellular and mitochondrial health. A concept named mitohormesis has been studied, which could promote lifespan and healthspan. A 2014 research article reviewed over 500 publications and found that, “Increasing evidence indicates. . .reactive oxygen species (ROS), consisting of superoxide, hydrogen peroxide, and multiple others, do not only cause oxidative stress, but rather may function as signaling molecules that promote health by preventing or delaying a number of chronic diseases, and ultimately extend lifespan.

“While high levels of ROS are generally accepted to cause cellular damage and to promote aging, low levels of these may rather improve systemic defense mechanisms by inducing an adaptive response.” Many call this the Goldilocks Zone – not too little, not too much. You may find a theme after reading our last few blogs: Calorie restriction and physical activity are two of the most substantial ways to maintain this balance.

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!

The capacity of our bodies to sense and respond to the ebb and flow of nutrient levels is vital to sustaining life. As we age, our body shifts in how its cells respond to the number of nutrients available.

. . .

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 already: genomic instability, telomere attrition, epigenetic alterations, and loss of proteostasis.

The next three hallmarks of aging are called antagonistic. Their role 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 thus accelerated aging.

The fifth hallmark, and first of the antagonistic, is deregulated nutrient-sensing. Our bodies contain complex regulatory mechanisms that measure nutrient scarcity or abundance. This process tells our cells whether to grow or whether to clean up and repair. This is based on the information it gets from hormone and protein signaling pathways.

The body’s balancing act

Metabolism is every biochemical reaction that goes on in your body. It converts food into the energy that sustains life, and there are specific proteins in the body that cause these reactions. When it comes to eating, your body uses a never-ending cycle that breaks down nutrients in food, rebuilds them, and then breaks them down again.

Energy is required for anabolism, or constructive metabolism, which is the process that builds new cells, maintains body tissues, and stores energy for later use. When your body is in an anabolic state, special enzymes separate the smaller molecules in your food, such as amino acids and glucose. These compounds are absorbed into the blood and carried to the cells, where they are either stored in body tissues such as the liver, muscles, and body fat or used for energy.

Energy is released during catabolism, or destructive metabolism, which is the process that generates the energy needed for all other cellular activities, including repair. When your body is in a catabolic state, it breaks down those complex molecules in order to release the energy you need for fuel. This then feeds the cycle that enables anabolism to begin again.

Building it up

We have evolved to be able to transition between anabolic and catabolic states, which has allowed us to survive and grow in environments in which nutrient availability is variable. One of the ways that our bodies do this is a signaling pathway controlled by a protein kinase, or enzyme, called mTOR.

mTOR controls cell growth, movement, and survival, as well as protein synthesis, autophagy, and transcription (how a cell copies its information when it’s ready to divide). It is adaptable and coordinates cell activity based on cues from the environment, such as nutrients, or lack thereof, and growth factors. It is ultimately responsible for the sensing of high amino acids concentrations.

Insulin-like growth factor-1 (IGF-1) primarily works with growth hormones to promote development in bone and tissues. IGF-1 uses the same signaling pathway as insulin, which tells the cells that glucose is present. This is known as the “insulin and IGF-1 signaling” (IIS) pathway, which is the most conserved age-controlling pathway throughout evolution. The IIS pathway regulates metabolism, growth, tissue maintenance, and reproduction in response to nutrient abundance.

When nutrients are abundant, the mTOR and IIS pathways work in tandem to form a network that helps to keep the body in an anabolic state that promotes cell growth and building. Conversely, mTOR is inhibited when nutrients are limited, which puts the body in a catabolic state and allows for cellular clean-up and repair.

Breaking it down

You may remember from a former blog that adenosine monophosphate-activated protein kinase (AMPK) acts like the body’s cellular housekeeper. It is what inhibits mTOR to promote catabolism. AMPK senses low energy states by detecting high AMP levels. AMP (adenosine monophosphate) is the end product of energy production.

Sirtuins are a family of proteins that regulate cellular health and they’re made by almost every cell in the body. They only function properly in the presence of nicotinamide adenine dinucleotide (NAD+), which is an essential cofactor in the production of energy by the mitochondria inside the cell and in energy metabolism.

Together, AMPK and sirtuins signal nutrient scarcity and catabolism. AMPK boosts NAD+, which in turn activates sirtuins. This initiates autophagy and the cellular housekeeping process begins.

You are what you do AND don’t eat

Sirtuins, mTOR, and the IIS pathway are all connected and respond to nutrient availability. One major way is via AMPK, and when it is activated, it prompts a cascade of complex interactions. Their functions fluctuate depending on the metabolic state of our body at any given time, thus their being labeled as part of the antagonistic hallmark of aging: deregulated nutrient-sensing.

Lopez-Ortiz et al concluded in their landmark paper, The Hallmarks of Aging, “Collectively, current available evidence strongly supports the idea that anabolic signaling accelerates aging, and decreased nutrient signaling extends longevity.”

Dietary restriction (DR), such as intermittent fasting or the fasting-mimicking diet, is the only intervention that has consistently been shown to increase lifespan. While we are still learning exactly why and how this is the case, the above-referenced research is showing that the sensing of nutrients plays an important part. We know that part of the reason dietary restriction works is by obstructing mTOR and the IIS pathway and activating AMPK and therefore sirtuins. 

In our blog on autophagy, we explained that intermittent fasting means becoming conscious of the times you choose to eat and increasing the time you’re not consuming calories. It is also known as time-restricted eating. Valter Longo, Director of the Longevity Research Institute, helped popularize what he calls the fasting-mimicking diet. His research showed that mice that fasted intermittently had improved life spans, reduced inflammation, increased cognitive ability, and that this mechanism could be used in humans for similar results.

Dietary restriction is an effective way to increase your lifespan and your healthspan. It has been proven, and while it takes a lifestyle adjustment, it is possible for your choices to have a direct impact on how you age.

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!

Cells need protein to grow and repair. Our bodies have safety measures in place to keep the production of proteins stable and without defects. However, sometimes these measures fail. This can lead to a cascade of errors that contribute to one of the primary causes of aging.

. . .

The biological definition of aging is the many processes of cellular damage accumulation in the body and these are known in the scientific literature as the Nine Hallmarks of Aging. The first four hallmarks are considered primary since they are believed to be actual causes of aging and have a definitively negative effect on DNA. The fourth hallmark, and the last of the primary, is loss of proteostasis.

Loss of proteostasis happens when the protein-building processes in the body go awry and the systems that eliminate damaged proteins malfunction. This leads to the accumulation of excess proteins, where they begin to cluster and cause disease, such as Alzheimer’s.

Transcribing the code

In our previous blog on genomic instability, we illustrated how our DNA contains the genetic instructions for making proteins. And our telomere attrition blog described the smaller units of DNA called nucleotide bases. In a process called transcription, when a cell is ready to copy its information, an enzyme called RNA polymerase binds to the DNA in a region known as the promotor.

In a manner similar to unzipping, RNA polymerase moves along the DNA making an exact, but opposite single strand of messenger RNA. The order of the bases is determined by the DNA code. The DNA continues to unwind ahead of the messenger RNA and rewinds behind it. The RNA polymerase enzyme helps to stabilize the molecules while the DNA is open, or unzipped.

Translating the code

Once the whole gene has been read, the messenger RNA travels out of the nucleus into the cytoplasm, a gel-like substance inside the cell membrane. Protein factories called ribosomes then bind to the messenger RNA. The ribosome reads the code in blocks of three bases at a time, known as codons.

Each codon contains instructions for one of 20 different amino acids. The ribosome then produces a chain where the corresponding amino acids are strung together. The sequence and chemical reactions along the molecule allow it to fold, twist or coil into elaborate structures called polypeptides, which create protein. Each structure has specific functions within the body.

The building blocks of life

Proteins do much of the work inside the cells and are responsible for the structure, function, and regulation of the body’s tissues and organs. They can be described according to their large range of functions in the body, listed in alphabetical order:

Examples of Protein Functions

FunctionDescriptionExample
AntibodyAntibodies bind to specific foreign particles, such as viruses and bacteria, to help protect the body.Immunoglobulin G (IgG)
EnzymeEnzymes carry out almost all of the thousands of chemical reactions that take place in cells. They also assist with the formation of new molecules by reading the genetic information stored in DNA.Phenylalanine hydroxylase
MessengerMessenger proteins, such as some types of hormones, transmit signals to coordinate biological processes between different cells, tissues, and organs.Growth hormone
Structural componentThese proteins provide structure and support for cells. On a larger scale, they also allow the body to move.Actin
Transport/storageThese proteins bind and carry atoms and small molecules within cells and throughout the body.Ferritin
Courtesy of MedlinePlus from the National Library of Medicine

Proteostasis

Proteostasis, or protein homeostasis, is a balanced state in which the cellular pathways required to produce proteins works flawlessly. This state is maintained by a system that adapts to meet the requirements of the cell, known as the proteostasis network (PN).

A 2020 research review states that the PN “comprises the machineries for the biogenesis, folding, conformational maintenance, and degradation of proteins with molecular chaperones as central coordinators.” This means that from the creation of a protein to its maintenance to its deterioration and ultimate removal, the PN is intricately involved in upholding the integrity of the entire proteome.

The PN does this sophisticated work using the following elements:

·  Ribosomes – translate RNA into proteins.

·  Chaperones and folding factors – guide polypeptides into the appropriate structures.

·  Degradation components – direct lysosomes to digest and recycle unwanted proteins. They can also include ubiquitin, a medium-chain polypeptide that is involved in the synthesis of new proteins as well as the destruction of defective ones.

Loss of proteostasis

As we age, our ability to sustain the essential process of proteostasis dwindles. The complexity and importance of this cannot be overstated. Internal and external stress can cause the unfolding of proteins or the improper folding during protein synthesis.

This inevitably leads to clustering and clumping, and eventually the accumulation of damaged and harmful proteins. All of this results in proteotoxic effects, which Sandri and Robbins refer to as “the adverse effects of damaged or misfolded proteins and even organelles on the cell.”

The good news is that there are “promising examples of genetic manipulations that improve proteostasis and delay aging in mammals.”

Until then, I have an opportunity

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!

Change is inevitable, but your choices can alter the path. Epigenetics literally means ‘above genetics.’ Epigenetics can’t change your DNA, but it has the potential to change the way your genes are expressed.

. . .

Epigenetics is one of my favorite topics. I have written about different aspects of epigenetics in two blogs in the past: How To Control Your Gene Expression and The Key to Reversing Your Biological Age. This week, we will explore the more technical side of the third hallmark of aging, epigenetic alterations, and how it contributes to the acceleration of aging.

In their landmark paper, The Hallmarks of Aging, Lopez-Ortiz et al composed three requisites and criteria that each hallmark should fulfill: “(i) it should manifest during normal aging; (ii) it’s experimental aggravation should accelerate aging; and (iii) its experimental amelioration should retard the normal aging process and, hence, increase healthy lifespan.” While each of the nine hallmarks meets these criteria in varying degrees, epigenetic alterations give us significant examples of all three.

Our DNA’s package

Before we elaborate, we must delve a little deeper into our biology lessons to get to the foundation of this hallmark of aging.

If you took a single DNA molecule and spread it out in a linear fashion, it would measure about six feet in length! In a human cell, this must be packaged into the nucleus of a cell with a diameter less than a human hair. So it goes without saying that our bodies have to do some pretty miraculous work to fit 46 of our 6-foot DNA molecules into the nucleus of every cell. And remember, we have approximately 30-40 trillion cells in our bodies!

In order to do this, the DNA must obviously be condensed. We’ve mentioned that our double-helix DNA is tightly woven around proteins. These proteins are called histones, and our cells wrap about 150 base pairs of DNA around a group of eight of these histones together – known as the histone octamer – to form what’s called the nucleosome. These resemble beads on a string, and they continuously spiral to form what’s known as the solenoid, which then supercoils further and stacks together to form a single fiber known as the chromatin. The end result is compacted DNA, histones, and a percentage of RNA, and the final condensed structure of this process results in the chromosome.

Chromatin is important because it strengthens the DNA to withstand cell division. It also allows for DNA replication, transcription (the process of making an RNA copy of a gene’s DNA sequence), DNA repair, and genetic recombination (diversity).

Our genetic on/off switch

There are many epigenetic alterations that affect our cells throughout our lifetime. The first change is what has been observed in DNA methylation patterns.

Remember that DNA is made up of nucleotide bases that form pairs of adenine (A), guanine (G), thymine (T), and cytosine (C), which in turn spell out our genetic code. One way that the body regulates how those genes are expressed is through a process called methylation. DNA can be tagged, or marked, with tiny molecules called methyl groups at some of its cytosine (C) locations. Like a switch, this literally silences that section of the gene, which can allow for normal cellular differentiation when we are developing as a fetus.

As we age, methylation can be thought of as a way for DNA to adapt to the never-ending changes in our environment – for better or for worse. The methyl groups need to be in the right place at the right time. It is when the methylation patterns become disrupted that things start to go awry. For example, some cancer cells are known for methylating areas of the DNA that are usually protected, and vice versa, which ultimately leads to abnormal suppression of activity in our DNA and thus, our gene expression.

Our genetic volume control

Another change that has been observed as an epigenetic alteration is modification of histones.

Remember the histone proteins and chromatin formation we mentioned earlier? Histones are not only one of the primary components of the chromatin but are also integral in the regulation of gene expression. They can alter how tightly or loosely the DNA is wound around them – the looser they are, the more the genes expressed; the tighter they are, the less genes expressed – similar to how a knob would control volume. Abnormal modifications of histones have been correlated with various diseases, including cancer, autoimmune disorders, inflammation and neurological conditions.

Our structural integrity

A third change that is characteristic of epigenetic alteration is chromatin remodeling. The chromatin’s tight coiling structure condenses and protects our DNA. It also prevents DNA from being transcribed continuously. However, in order for genes to be accessed and expressed, they must ‘open’ in a process known as chromatin remodeling. This is crucial for proper cell functioning.

In aging cells, enzymes that are involved in the DNA methylation and histone modification processes start to fade. This results in loss of integrity within the chromatin. Since the strength of the chromatin is necessary for DNA replication and repair, it becomes apparent that deterioration of this important structure can adversely affect the aging process. When the chromatin remodeling process starts to decline, epigenetic abnormalities accumulate, which can result in diseases such as cancer.

Food is medicine

In my best-selling book, The Longevity Equation, I indicate, “Research shows that epigenetic alterations can be slowed down by including plenty of bioactive compounds in your diet. You can do this by consuming healthy fruits, vegetables, seeds, nuts, and oils.”

There is also research that these bioactive compounds alter DNA methylation and histone modifications and have the ability to favorably alter gene expression and prevent tumorigenesis. Foods particularly effective include turmeric, soybean, green tea, grapes, and cruciferous vegetables, such as broccoli and cauliflower. The authors state, “The emerging field of nutritional genomics targets nutrient-related genetic and epigenetic changes for prevention and therapy of various diseases including cancer.”

Find out your epigenetic age

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!

We have a sophisticated and specialized part of our DNA that protects all of the genetic information in our cells. Let’s take a look at how the break-down of these important complexes contributes to the acceleration of aging.

.  .  .

I’ve said it before, and I’ll say it again: Age is the number one independent risk factor for all chronic diseases. The biological definition of aging is the many processes of cellular damage accumulation in the body and these are known in the scientific literature as the Nine Hallmarks of Aging. I’ve also talked about how the first four hallmarks are considered primary since they are believed to be actual causes of aging and have a definitively negative effect on DNA.

We talked about the first hallmark of aging, genomic instability, in our last blog. This week, we will look at the second hallmark of aging: telomere attrition. In order to understand what this particular process of aging means, we must again revisit high school biology.

The rungs on the twisted ladder

Our DNA is made up of smaller units called nucleotide bases. There are 4 bases: adenine (A), guanine (G), thymine (T), and cytosine (C). Each of these bases forms a pair that shows the iconic visual of rungs on a twisted ladder. Adenine forms a base pair with thymine, and cytosine forms a pair with guanine. These base pairs spell out a letter code that allows the DNA to function in different ways in our bodies.

Remember that our DNA carries our genetic blueprint or instructions in the form of genes. Our DNA is tightly woven around protein to structure our chromosomes, which are found in the nucleus, or control center, of our cells.

Now picture the rungs of base pairs on that twisted ladder – there are millions of them. The middle section of rungs is made up of long stretches of our genes. The last few thousand rungs on ends of that twisted DNA ladder are called telomeres. They are repetitive, short sequences of non-coding nucleotide bases, bound by a special protein called shelterin. They protect the ends of our DNA, and thus our genetic information, in the same way, that the aglets, or plastic tips, on our shoelaces keep them from fraying.

This is extremely important as we age and our cells divide to produce new cells to replace those that are old and worn-out. Telomeres allow our cells to divide, and thus our DNA to replicate, without harming our genetic information. They do this by preventing the ends of chromosomes from fusing together, which would cause considerable genomic instability.

Telomeres do this with the help of the aforementioned protein called shelterin, which masks the ends of the chromosomes and suppresses the signaling process in the body that cleans up damaged DNA. The enzyme telomerase also helps to replenish the repetitive telomere sequences during each cell cycle.

Good things don’t last forever

This amazing protective mechanism in the body sadly does not last forever. In my book, The Longevity Equation, I point out that, “Our natural DNA replication mechanisms do not duplicate all of the telomeres when each cell divides, so each chromosome has fewer telomeres. Once the telomeres run out, you hit what’s called a cell growth arrest. This means you are limited to how much new tissue you can regenerate as you age.” Some say that telomeres are the molecular clock that stops cell division.

Each time a cell divides, 25-200 bases are lost from the ends of the telomeres on each chromosome. As telomeres start to fray and become shorter, they start to resemble broken DNA and become more likely to be targeted by a process called DNA damage response (DDR), which ultimately leads to cell death. Shorter telomeres are associated with most diseases of aging in humans.

Maintenance requirements

Telomerase is an enzyme that adds DNA to the ends of chromosomes, which helps maintain chromosomal length. However, it is only found in low concentrations in somatic cells (any cells other than the reproductive cells) but in high concentrations of stem cells and germ cells (egg and sperm). For this reason, as we age, our telomeres reduce in normal function. Unfortunately, telomerase is also found in high levels in cancer cells, which enables these cells to divide indefinitely.

What all of this means is that we need to have enough telomerase activity to keep our cells healthy and prevent them from degrading prematurely, but not so much that it contributes to the growth of cancer cells. So in a word: moderation.

If our cells are exposed to stress or injury – such as hormonal stress, inflammatory stress, and oxidative stress – they will be forced to divide more frequently, and consequently, our telomeres will shorten more quickly. The end result: accelerated aging.

Some easy ways we can maintain our telomere length, and possibly extend them:

·  Regular, moderate exercise

·  Stress reduction

·  Healthy diet

·  Weight loss

·  Smoking cessation

Let us provide you with guidance

Since telomeres are essential in cellular functioning, they continue to be actively researched as a therapeutic intervention in nearly every known disease state. They are considered a biomarker of aging, and thus we have the ability to test and measure telomeres directly. However, because of their direct and significant role in genomic instability, we suggest another way of looking at the current state of your DNA.

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!

Ever wonder what causes ‘gut feelings’ and ‘butterflies’ in your stomach? Or why your stomach gets upset when you’re worried or fearful? There is an elaborate and intriguing system in our bodies that connects and communicates without any effort on our part!

.  .  .

Our microscopic friends

In an earlier blog, we pointed out that your unique microbiome is so important that it is considered a hidden organ by some researchers. It started as soon as you were born, if not before, and is continually influenced by your diet, your experiences, what you’ve been exposed to and where you live. We also illustrated how vital it is to keep your microbiome healthy, and what can happen when this community of microorganisms gets tipped out of balance.

We depend on these complex social networks of microorganisms to help break down nutrients and produce important vitamins and enzymes in our digestive system, which in turn strengthens our immune system. And although it might seem strange, it has been shown that our microbiome is intricately linked to our central nervous system (CNS) through neural, hormonal, metabolic, and immunological signaling pathways.

Another brain?

Just as fascinating is that hidden in the walls of our digestive systems is our enteric nervous system (ENS), referred to as the ‘second brain,’ due to its ability to operate independently of the central nervous system. While researchers are still learning exactly how the ENS works and the full extent of its functions, we do know that the ENS plays a significant role in disease and mental health.

The main role of the ENS is to control digestion from start to finish. But because of its ability to also communicate with our brain through the central nervous system and autonomic nervous system (ANS), researchers are now finding that people with gastrointestinal symptoms may experience mood changes as a result. We outlined the ANS and its two branches, the sympathetic and parasympathetic nervous systems, in our last blog on stress.

Our communication channel

Our microbiome, central nervous system, autonomic nervous system, enteric nervous system, immunological and neuroendocrine systems all interact to comprise what’s called our gut-brain axis. An essential role of this multidirectional interaction is to help the body maintain metabolic homeostasis.

Signals are sent back and forth between the gut and the CNS, which causes the hypothalamus and brain stem to regulate how your body consumes and uses energy. In addition, since roughly 70% of our immune system is in our gut, the gut-brain axis also allows our brain to monitor the interactions taking place between our immune cells and our microbes, hormones, and neuronal cells in our gut so it can respond to changes if needed.

Our multi-tasking wonder nerve

A special and significant part of our parasympathetic nervous system, and ultimately our gut-brain axis, is the vagus nerve. On page 165 in my book, The Longevity Equation, I mention that “The vagus nerve is the longest cranial nerve in the body. It runs through the brain stem, esophagus, lungs, heart, digestive tract, and all the way down to the colon.” 

When we are not stressed, the vagus nerve serves as a communication superhighway, sending sensory information from the peripheral system to the brain so it can monitor function, and transmitting motor signals from the brain to the rest of the body.

The vagus nerve has immunomodulatory properties and therefore it “plays important roles in the relationship between the gut, the brain, and inflammation.” It stimulates muscles in the heart, almost like a natural pacemaker, where it helps to lower resting heart rate. In the gut, the vagus nerve can even let our brains know the status of our microbiome!

A healthy vagus nerve helps us to access parts of the brain responsible for creativity, higher cognition, and complex decision making. As you can see, this nerve has a critical place in our bodies, affecting our thoughts, many internal organs, and our gastrointestinal system. Some say it is the key to our well-being.

Why is all of this important?

The function of the vagus nerve can be impaired by anxiety, poor lifestyle, smoking, alcohol and overworking, as well as lack of proper nutrition, exercise, and sleep – basically whenever the body is in a state of stress.

Simply put, stress inhibits the vagus nerve and stimulates the sympathetic nervous system to initiate the ‘fight or flight’ response. Since the vagus nerve plays a role in reducing inflammation, stress can conversely cause inflammation. Therefore, repeated and increased exposure to stress can counteract the parasympathetic system’s ability to help the body recover and contributes to allostatic load, which is the wear and tear of stress on your body and brain. In the end, this could hinder the overall protective effect that the vagus nerve has on the body.

This has particular effects in the gut where an inhibited vagus nerve has harmful effects on our microbiota and contributes to gastrointestinal disorders such as leaky gut, irritable bowel syndrome, and inflammatory bowel disease. This disrupts our metabolic homeostasis and has a cascade of effects on the body. Consequently, it is imperative to do what we can to maintain a healthy and functioning vagus nerve.

Restoring the gut-brain axis

Bringing this full circle, there is an abundance of ways that we can create and bring balance to our all-important gut-brain axis, one of the most significant communication pathways in our bodies. We can monitor our vagal tone, supplement with high quality prebiotics and probiotics, meditate, practice deep breathing, and exercise.

Ways to strengthen vagal tone:

·   Gargling vigorously with water after you brush your teeth every morning can strengthen your vagus nerve. This will help improve movement in your digestive tract and can help with constipation and a sluggish bowel.

·   Chanting, humming and singing out loud help to activate the vagus nerve. Next time you’re in your car, sing as loud as you can!

·   Deep breathing helps to lower blood pressure and heart rate. Inhale for the count of five, and exhale for a count of five for one minute. This then sends a signal to the brain to stimulate vagal activation and put us in a rest and digest state, rather than fight or flight.

·   Tongue depressors stimulate a gag reflex and strengthen the vagus nerve similar to gargling. You can also use your toothbrush and brush your tongue far enough to produce a gag reflex.

·   For the busy person, there’s one simple way to stimulate the vagus nerve, and it takes just 5 seconds to do. If you find yourself feeling sleepy, stressed, or lacking focus, you can use this to retune your nervous system. Here’s how it works: take a long deep breath, filling your lungs completely with air, and then let it out slowly. It’s that simple. Try it for yourself.

How can The Institute for Human Optimization assist me?

We believe 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.

At The Institute for Human Optimization, my team and I leverage the most cutting-edge advances in genetic testing, nutritional, and functional medicine to help our patients treat the root biological imbalances that cause aging. I 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.

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.

Let’s work together to keep that communication open!