Human Optimization

PROTEOMICS: THE TRANSLATION OF OUR BLUEPRINT

The technology surrounding proteomics has evolved in recent years providing promising new directions to study for future clinical application and in the pursuit of precision medicine. Moreover, advanced proteomic technology has allowed researchers the platform to improve our understanding of biology.

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What is proteomics?

Proteomics refers to the study of proteomes. Proteomes are the entire set of proteins that are expressed by an organism. Proteins are responsible for the function of the cells. Since protein is the main element in food, and with proteins being fundamental to cellular function, proteomic technology can successfully identify the protein content of food, assessing their protein biomarker, and how they change during their production. 

Application of Proteomics in Medicine

Currently, proteomics is being used extensively for biomarker discovery. Biomarkers is defined by the National Institute of Health Biomarkers Definitions Working Group as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” It is a means to a facet of health.

With proteomic technology, we look at proteomic expression to identify protein biomarkers of disease. Biomarkers can be categorized as diagnostic, prognostic, predictive or predisposition biomarkers.

  • Diagnostic: Diagnostic biomarkers are used to confirm that an individual has the presence of a specific disease or health disorder.
  • Prognostic: A prognostic biomarker can showcase how disease will progress when an individual has been diagnosed with a specific disease or health disorder.
  • Predictive: A predictive biomarker is used by clinicians to help determine how well a treatment will work for the individual.
  • Predisposition: A genetic predisposition biomarker is a biomarker that indicates a susceptibility for that individual to develop a specific disease or heath disorder.

Techniques used in Proteomics

Most approaches in proteomic analysis use a bottom-up or top-down approach.

Bottom-up proteomics: is also considered a peptide-level approach as samples are characterized by their amino acid sequences prior to analyzing.

Top-Down proteomics: Unlike bottom-up that digests proteins into peptide sequences, Top-down proteomics analyzes proteins intact. By bypassing the protein digestion step this method is considered less time consuming and simpler.

What are some of the techniques used for proteomic analysis?

  • Ionization: There are two main methods used for the ionization of protein. One is Electrospray Ionization (ESI) is a technique where a high voltage is applied to a liquid to create an aerosol. The other is the matrix-assisted laser desorption ionization (MALDI) that uses a laser energy absorbing matrix to create ions from large molecules with minimal fragmentation. While different techniques are both used in the proteomic analysis by looking at how proteins and peptides react.
  • Analyte Quantitation Methods: Analyte quantitative methods are techniques used to determine the number of proteins in a sample as well as differences between biological samples. This is used to compare samples between healthy and disease patients as well as to identify and quantify changes in individual proteins.

Clinical Applications

Proteomics is used in a host of clinical scenarios from common disease diagnosis and management to the diagnosis of cancer. These biomarkers are used to help assess clinical responses to medical interventions and gauge the severity of illness. For example, hs-CRP is used to assess cardiovascular inflammation. When these protein is elevated in circulation its associated with an increased risk for heart disease and stroke in people who don’t already have it.

Future of Healthcare

This Omics in medicine is important as it improves our understanding of biology by allowing us insight into the vitality of cells. As the vitality of a cell changes, these changes are visible at the proteomic level. Techniques in the proteomic analysis are seeing changes in protein profiles being a future predictive diagnostic tool to assess disease. While technology is advancing, the use of proteomics in healthcare is still very much considered in the discovery phase as full integration is still under works. While we have not reached full clinical utility, the benefits and potential uses are promising with technology rapidly evolving. As medicine continues to advance, the use of proteomics will be a part of precision, personalized approach to medicine.

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.

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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OMICS OF MEDICINE: Transcriptomics

A gateway to a better understanding of disease pathogenesis.

As technology in genomic analysis has enhanced, so has our ability to learn about DNA, RNA, and how they react as we age. With recent developments, we can provide more precise medicine and utilize transcriptomics as a gateway to a better understanding of disease pathogenesis. 

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What is Transcriptomics?

Transcriptomics is the study of the transcriptome, that covers all 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.

In the ’90s this field was originated to study gene expression. Gene expression is defined as the conversion of DNA into protein by the process of transcription and translation. DNA is first transcribed into mRNA which is then translated by cells into different proteins. This phenomenon is known as the central dogma of molecular biology.  

 All RNAs are not translated into proteins. Some remain in the cell and serve different functions. Like rRNA (Ribosomal RNA) is a structural RNA and makes up the ribosome. They are also transporters like tRNA (transfer RNA) and transports amino acids for the formation of proteins. Some are also regulatory which include siRNAs and IncRNAs. If the gene is abnormally expressed, then abnormal mRNA transcript and ultimately abnormal protein will form. These things are studied in transcriptomics and also in genomics and proteomics.

Techniques used in Transcriptomics:

The two techniques used in transcriptomics are microarrays and RNA sequencing (RNA-Seq). Microarray is a lab technique used for the detection of the expression of thousands of genes in a single reaction quickly and efficiently. The quantity and sequences of RNA in a sample can be examined using RNA sequencing which is a Next-Generation Sequencing (NGS). 

Microarray: Microarray technology was created by a team led by Dr. Schena at Stanford University. This high-tech technology has revolutionized medicine by giving us insight into the human genome. Microarrays are used for analyzing transcriptomes. It is used to detect the expression of thousands of genes at a time. They detect only known sequences. They are not used for the discovery of new sequences. Microarrays are a recent technology and are used for cancer research. It is also used for drug development and clinical research. A part of the genome with missing or extra genetic information can be detected using Microarrays.

RNA sequencing: It analyses the transcriptome of gene expression and allows us to discover and investigate the transcriptome. This technique tells the scientists which genes are on and which are off. Also, it determines the level of expression of genes in a cell. RNA helps to determine the biology of the cell. If any unusual changes are present in sequencing, a disease is indicated. The techniques in which RNA sequencing is used are transcriptional profiling, SNP identification, RNA editing, and differential gene expression analysis. RNA sequencing is a revolutionary tool for transcriptomics. RNA-Seq uses deep-sequencing technologies. 

Precision Medicine: In precision medicine, clinicians look at your bio-individuality, environment, lifestyle, and more to select the optimal therapy for you. Genomics and transcriptomics involved in precision medicine can be used for determining the accurate and reliable treatment for different diseases. For the determination of disease pathways and accurate treatments, a study of genomics and transcriptomics is essential.

Applications of Transcriptomics in Medicine:

Stem Cell and Cancer Research: Intratumor heterogeneity is a challenge to the treatment of cancer as it shows therapeutic resistance and undergoes metastasis. (Spread of cancer) Transcriptomics helps in the identification of such types of aspects in cancer research. A highly heterogeneous disease, Cancer, is driven by molecular aberrations at the genetic, epigenetic, transcriptomic, and protein levels. 

Transcriptomics combined with proteomics is one of the most promising approaches for the investigation of stem cell biology. Stem cells have the property of self-renewal and differentiation and so the mechanisms that regulate these processes are widely studied. Stem cell studies using transcriptomics will promote the clinical applications of stem cells. 

  • Embryogenesis and In-vitro Fertilization: The development of an embryo after fertilization of sperm with egg is called Embryogenesis. In vitro is the artificial technique for producing offspring. In In-vitro fertilization, mRNA is injected into the zygote and so transcriptomics is involved in this process.
  • Characterization of non-coding RNAs:  Non-coding RNAs are those molecules that are not translated into proteins. Non-coding RNAs have been found in various biological and pathological processes. Transcriptomics is used to find the role of these RNAs in any disease.
  • Detection of Transposable Elements in Genome: The sequence of DNA that can change its position within the genome is called a transposable element. It can create or reverse mutations and can also alter the cell genome’s size. Transcriptomics is used for the detection of transposable elements in the genome.
  • To produce Epigenetic Alterations: Epigenetics is the inherited genetic alterations that are not the result of changes in DNA sequence. At the level of transcription, genetic expression is influenced by epigenetic processes.
  • Role in Precision Medicine: In transcriptomics, it is studied how living organisms and their transcriptomes respond to diseases and environmental factors. The study of transcriptomes is very important in discovering the pathways of disease and for the development of effective drugs. The difference in the same disease has been studied in different people at the genomic level. In the early stage of disease, precision medicine can play a preventive and predictive role. 
  • Pharmacogenomics: The effects of genetic differences on drug metabolism are studied in Pharmacogenomics. It is one of the important applications of Transcriptomics. Due to genetic differences, different individuals respond differently to the drug. According to the genotype of the person most appropriate dosage is prescribed to the patient. Transcriptomics helps in Pharmacogenomics studies and processes.
  • Role in Disease Determinants and Causes: Screening of diseases and their causes can be determined using transcriptomics. This is of great use as this helps in the detection of complex diseases like breast cancer, acute myeloid leukemia, and cardiovascular diseases.  

Future of Healthcare

Transcriptomics is one of the fields undergoing massive research as researchers aim to understand better how changes in transcriptional activity can influence disease. In transcriptomics, the focus is on the mRNA of the gene expression. Causes of genetic disorders can be identified using transcriptomics. RNA analysis helps in the determination of disease and treatment markers and also the response of the genome to different drugs for treatment purposes. 

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. Additionally, we use the latest technology to test your blood markers, biome, and genetics, to create a health plan tailored just for you. We use a genome to phenome approach to your care. 

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 to pursue 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 health span – not just a long lifespan – is the most important thing you can cultivate. A long health span 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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OMICS OF MEDICINE: GENOMICS

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!

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THE OMICS OF MEDICINE

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.

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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!

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ALTERED INTERCELLULAR COMMUNICATION – Where Inflammation Meets Aging

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 CELL EXHAUSTION – The Ultimate Culprit of Aging

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!

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CELLULAR SENESCENCE – When Cells Undermine Their Purpose

Our bodies have a built-in process that is believed to be a protective mechanism called cellular senescence. As we age, this process slows down and can result in disease.

. . .

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

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

The miracle that is us

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

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

Our cell cycle has four stages:

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

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

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

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

 A fine line between helping and hurting

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

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

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

Crossing the threshold

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

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

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

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

Can we clean up the excess?

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

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

What else can I do?

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

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

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

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

More about The Institute for Human Optimization

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

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

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

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

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

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

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

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

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

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

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MITOCHONDRIAL DYSFUNCTION: Our Powerhouse Gone Awry

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!

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DEREGULATED NUTRIENT-SENSING – A Fine Line Between Longevity and Aging

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!

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LOSS OF PROTEOSTASIS – The Breach of our DNA Security

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!

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