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!