CELL MEMBRANE: Protection for the Cell

Every cell in the body is protected by a membrane. Cell membrane creates a protective barrier that shields the outside elements from the internal components of the cell, organelles. By understanding the cell membrane and what it needs, we can support our cells and cell membranes and consequently optimize our overall wellness.

The cell membrane has been historically characterized as having a fluid-mosaic model which allowed for selective permeability of various agents into the cell. Importantly, cell membrane integrity is essential to cell viability and function. Cell membranes are responsible for maintaining electrochemical gradients with a negatively charged intracellular composition and positively charged extra-cellular environment. This gives rise to what is known as the Resting Membrane Potential (RMP) and is responsible for every single physiological event that takes place within the body.  Additionally, these dynamics are a key factor in the rate of aging especially within brain cells, known as neurons.

Cell membrane structure and its function.
Cells are the building blocks of life. We each have trillions of cells throughout our bodies that provide structure for the human body, take in nutrients, convert nutrients into energy, and perform specialized functions. The cell membrane, also known as the plasma membrane, is the envelope lining of the cell that shields the cell but carries important functions.

Cell membrane provides vital functions in the maintenance of cell activities including:
• They protect from toxic substance out of the cell
• Contain pathways that allow specific molecules to enter and leave the cell such as ions, nutrients, waste via transmembrane proteins.
• Separate vital metabolic processes conducted within little organs known as organelles.
• Communication
• Signal generation

Cell membranes are made up of proteins, and fats, also known as lipids. Lipids form the building blocks of cellular membranes with phospholipids being the most abundant type of lipid found in the membrane. Phospholipids are what support the cell membranes unique structure due to their hydrophobic (non-polar) tails and hydrophilic heads (polar). This means that heads of the molecules face outward and are attracted to water whereas the tails face inside away from the water allowing them to arrange themselves in a sphere form in aqueous solutions.

Cholesterol is another cell membrane component.  We often only hear about how cholesterol can build up in your arteries and cause heart disease but it’s important to acknowledge its function. Biologically speaking, cholesterol is critical for cell function and plays a vital role in membrane fluidity which is the ease with which lipids move within the bilayer of the cell membrane. About 25-30% of lipid in the cell membrane is cholesterol.

Role of Phospholipids
As previously mentioned, phospholipids play a critical role in insulating cell membranes. Two of the most important outer and inner leaflet phospholipids are phosphatidylcholine (PC) and Phosphatidylserine (PS). Supplementing with phospholipids is a part of a clinical strategy known as membrane lipid replacement and is a prudent measure in maintenance of overall cellular health and aging.

Role of lipids
In addition to phospholipid compounds, there is a select class of lipids, known as the Eicosanoids, that are liberated from the membrane, metabolized into an intercellular communication and information system by their prostaglandin regulatory activity. Prostaglandins, thromboxanes, and leukotrienes mediate inflammatory signaling and coagulation pathways within the blood.

Role of Protein
Proteins are the second major component of cell membranes. Proteins mostly contribute to the function of cell membranes but also play a small role in forming the structure of the membrane.

There are 3 main types of membrane proteins
1. Integral Membrane Proteins: also known as transmembrane proteins allow molecules such as nutrients and waste to enter and leave the cell and also transmit signals between the cells internal and external environments.
2. Peripheral Membrane Proteins: form a temporary attachment with the cell membrane by allowing the proteins to attach, detach, and reattach.
3. Lipid-anchored Proteins: anchor the protein to either side of the cell membrane promoting the function of the protein to which it is anchored to.

Proteins are what help the cells interact with its environment but also help transporting substances across the cell membrane.  

How to optimize cell membrane health

Now that we have a better understanding of the cell membrane structure, we can see how cell membrane integrity influences our overall health. Optimal health begins with an optimally functioning cell membrane structure. It is important to maintain a nutrient rich diet, antioxidants, and healthy fatty acids so that the cell membrane remains flexible to transport nutrients into your cells while eliminating the cells of waste. Additionally, a nutrient rich diet and healthy fatty acids is necessary for the nervous system and cardiovascular system and more.

What else can you do? Follow us along as we take a deep dive on cell membrane health during our Cell Membrane Series.

More about The Institute for Human Optimization

At the Institute for Human Optimization, 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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EXPOSOME: Measuring the biological impact of the environment around us

Our environment can drive disease or mitigate disease risk. As we look at medicine through the lens of a systems biology approach, most disease is a result of a complex interchange between genetic and environmental factors. 

.  .  .

The exposome is the sum of all the exposures of an individual in a lifetime and how those exposures relate to health. This term originated by Dr. Wild in 2005 introduced the concept to create awareness of the need to look at environmental impacts in epidemiological studies. 

The exposome makes up of all exposures from conception to death.

There are three areas of the exposome

  1. Internal Factors
  2. Specific External actors
  3. General External Factors

There are studies that show that even from conception, there is a link between exposures throughout pregnancy and fetal growth. When we look at the skin exposome, there are various internal and external factors that show a clinical presentation of skin aging. 

There are various types of environmental exposures that influence our health and aging including but not limited to:

  • Air quality
  • Tobacco
  • Sun Radiation
  • Pollution
  • Stress
  • Nutrition
  • Sleep Quality
  • Temperature
  • Heavy Metals
  • Mold
  • Pesticides

Exposures are from our external environment as listed above but also are a result of our internal biological processes. Internal exposures rely on the omics of medicine. You can learn more about the omics of medicine with our blog series linked here. Utilizing omics data we can measure internal exposures and explore how the exposome is linked with disease.

Exposome and Cellular Ageing

If you recall, in our Hallmarks of Aging series, we discuss cellular senescence and its role in aging.  Studies have shown that environmental exposures influence telomere length which is an indicator of cellular aging. Telomeres are the caps at the ends of the strands of DNA called chromosomes, which house our genomes. Telomere shortening is one of the most recognized biomarkers of aging. As cells divide, oxidative stress is considered one of the main factors contributing to telomere shortening. By the exposome influencing the shortening of telomeres, which in turn accelerates the process of aging by affecting our biological pathways that result in health decline. 

Application of Exposome in Medicine

Exposome research is currently being developed to better understand an individual’s health, recommending therapies, and how they will respond to such therapy. This concept targets your individual conditions that influence your health. These exposures integrate your social science, environmental, occupational on a cumulative individual level. From a medical perspective, when we look at the microbiome, which plays a critical role on the exposome, that is unique to each individual due to the variability in bacterial diversity for various environments. 

As you can imagine, there are complex challenges in accurately measuring the exposome of an individual. Additionally, your exposome can change throughout your lifetime which makes its analysis a life-long assessment in theory. These concepts have led to an approach that integrates the exposome and the genome known as the exposome-genome paradigm. By analyzing an individual’s exposome and genome, now leads to better insight for disease prevention.

The biological impact of the exposome is improving our understanding of the connection between exposures and health to help mitigate adverse health outcomes across the lifespan. Genetics only accounts for about 10% of disease leaving the rest to be related to environmental causes.  Exposome information is a key step in precision medicine and precision environmental health monitoring. 

More about The Institute for Human Optimization

The Institute for Human Optimization we believe that Omics-based medicine and systems biology taking into account your exposome 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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METABOLOMICS: Bridging the gap from genotype to phenotype

Today, we continue our series on the Omics of Medicine. If you have followed along, you will find that each Omic plays a key role in precision medicine. 

This week we are taking on an important Omics system: Metabolomics. While appreciated for its role in biomarker discovery, metabolomics has emerging applications towards personalized medicine, precision nutrition research, and even agriculture. 

.  .  .

What is metabolomics, the metabolome, and more?

Metabolomics is the large-scale study of small molecules, commonly known as metabolites, within cells, biofluids, tissues, or organisms. Metabolites are small molecules that are the end product of a metabolic process. Metabolites have several functions including but not limited to epigenetic influencing, fuel, structure, signaling, defense, and more!

Metabolites are either primary or secondary.

Primary: directly involved in normal growth, development, and reproduction of an organism. Examples include: Ethanol, Glutamic Acid, Acetic Acid, Glycerol.. 

Secondary: Is not involved in normal growth, development, and reproduction but serves   

an ecological function and its absences is detrimental to the organism.  Examples include: Peptides, Growth Hormones, Antibiotics, Alkaloids, and more. 

In humans, there are thought to be approximately 3000 common metabolites although researchers suspect that there are much more. The metabolome is the complete set of metabolites within a cell. Within a cell many reactions take place such as:

-Binding 

-Dissociation

-Degradation

-Modification

-Classic biochemical reaction

-Transport

These reactions are considered to be anabolic, where you are growing and/or building, or catabolic which is when you break down food and molecules for energy. 

Importance of Metabolomics

The metabolome is considered the closest link to the phenotype and thus, a critical omics discipline in the pursuit of personalized medicine. How? Recall that a phenotype is an individual’s observable traits (e.g, height, eye color, blood type). These traits are mostly determined by your genotype (your set of genes) or by the environment. A phenotypic variation is due to a variation in the genotype, the environment, and how the genotype and environment interact. Omics research is currently exploring how genetic effects on phenotype are being filtered through the metabolome, making it a critical omic to possibly bridge the gap between genotype and phenotype. This will be a powerful tool in informed decision-making, developing drugs, and preventative healthcare.

Uses Today & Future Applications

Precision Nutrition: Metabolomics has emerging applications with precision nutrition which has the goal of customized nutritional recommendations. Utilizing metabolomics data, researchers can make better nutritional recommendations.  For example,  utilizing metabolomic data, when we look at infant formula, it has been optimally formulated to mimic the molecular composition of human milk taking into account the distribution of fatty acids. 

Dietary Analysis: Researchers are using metabolites found in blood and urine to accurately measure dietary intake. This is a gateway to assess eating habits as currently the tools being used rely on our recordation and subject to human error.

Biomarker Discovery: Human metabolites being profiled has accelerated biomarker discovery.

Future of Medicine

Utilizing Omics data will provide us the lens for the molecular microscope to objectively examine individual variability. With metabolomics being used to identify metabolites that alter a phenotype, it is no surprise that many researchers consider metabolomics as the omics discipline closest to the phenotype.

The future of medicine is a precision base medicine approach that takes into account your bio-individuality, environment, lifestyle, and molecular phenotype to find the best clinical care option for you. 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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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.

.  .  .

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. 

.  .  .

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.

.  .  .

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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