The Role Of Mitochondrial And Metabolic Dysfunction in Ageing

What is Mitochondria?

Mitochondria are organelles that are found in most eukaryotic cells. They are responsible for generating most of the cell's energy, which is used for a variety of cellular processes. Mitochondria are also unique in that they contain their own DNA, which allows them to produce some of their own proteins.

The process of oxidative phosphorylation is how mitochondria generate energy. This process involves the breakdown of carbohydrates and fatty acids, which releases electrons. These electrons are then passed through a series of electron carriers, which ultimately results in the production of ATP. ATP is the cell's main energy currency, and it is used to power a variety of cellular processes.

Most mitochondrial proteins are translated on free cytosolic ribosomes and imported into the organelle by specific targeting signals. However, mitochondria also contain their own DNA, which encodes some mitochondrial proteins. This DNA is circular, and it is located in the mitochondrial matrix.

The assembly of mitochondria is a complex process that involves proteins encoded by both the mitochondrial genome and the nuclear genome. Proteins encoded by the mitochondrial genome are translated within the mitochondrion, while proteins encoded by the nuclear genome are imported from the cytosol.

Role of Mitochondria in the human body

Mitochondria are involved in calcium signaling, redox balance, and thermogenesis, making them an important cellular component that determines a cell's fate. Mitochondria go through a number of processes to maintain their quantity and quality, including fission, fusion, and mitophagy, to destroy or replace damaged mitochondria. While this bioenergetics machinery is adequately safeguarded, the functional loss associated with ageing and age-related metabolic disorders is mostly the result of such protective systems failing.

What is Mitochondrial Dysfunction?

When the mitochondria, the powerhouse of our cells, fail to function adequately, it leads to symptoms like extreme fatigue and other symptoms typically associated with various chronic diseases.

The decrease in mitochondrial functionality can be attributed to several factors:

(1) The inability to maintain the electrical and chemical balance across the inner mitochondrial membrane
(2) Disruptions in the workings of the electron transport chain
(3) The inability to transport essential metabolites into the mitochondria.

These issues collectively result in a less efficient oxidative phosphorylation process, thereby reducing the production of ATP (adenosine-5′-triphosphate). Certain elements of this system require regular replenishment, which can be achieved with the help of natural supplements.

Studies have demonstrated the efficacy of orally administered supplements such as l-carnitine, alpha-lipoic acid (also known as 1,2-dithiolane-3-pentanoic acid), coenzyme Q10 (ubiquinone), reduced nicotinamide adenine dinucleotide (NADH), membrane phospholipids, and other supplements. Using a mix of these supplements can significantly alleviate fatigue and other symptoms associated with chronic disease, and can naturally revitalize mitochondrial function, even in patients who have suffered from long-term, stubborn fatigue.

Correlation between mitochondrial dysfunction and aging

The process of aging is primarily characterized by a gradual, time-dependent decrease in the cellular and organ functions of living organisms, rendering them more susceptible to chronic illnesses and ultimately leading to mortality. Recent studies have identified nine potential signs of aging in mammals, divided into three main groups: primary hallmarks (including genomic instability, telomere attrition, epigenetic modifications, and the breakdown of protein homeostasis), antagonistic hallmarks (encompassing mitochondrial malfunction, disrupted nutrient sensing, and cellular senescence), and integrative hallmarks (such as stem cell depletion and altered intercellular communication). The primary hallmarks act as the root cause of molecular damage during aging, while the antagonistic ones have a protective effect at low concentrations but can be harmful in larger quantities. The integrative hallmarks, on the other hand, emerge when cellular balance fails to mitigate the accumulated damage. These aging signs are interrelated and affect cellular metabolism, implying that metabolic interventions might be a viable approach for promoting longevity and improving overall human health.

Mitochondria, crucial in controlling cellular metabolism and balance due to their roles in various biological functions including energy production, ROS generation, anabolism and catabolism, and signal transduction, among others, are essential for survival and can adjust metabolic processes in response to cellular stress. A variety of aging aspects, such as decreased oxidative phosphorylation (OXPHOS) activity, increased oxidative damage, reduction in mitochondrial quality control, and changes in mitochondrial shape and biogenesis, are associated with mitochondrial dysfunction. This dysfunction also plays a role in a wide range of age-related illnesses, including neurodegenerative and cardiovascular diseases, diabetes, obesity, and cancer. It is critical to maintain a delicate balance between creating new mitochondria and removing damaged ones to ensure cellular and mitochondrial stability. Mitophagy, a selective autophagy process that clears away damaged or dysfunctional mitochondria, and mitochondrial biogenesis, which generates new mitochondria, need to be well-regulated and coordinated. A complex regulatory network manages these processes, and its proper operation is vital for aging and longevity.

If mitochondria become dysfunctional or stressed, they generate signals initiating protective responses to prevent cell death and restore cellular and metabolic equilibrium. In this piece, I'll delve into the roles of mitochondrial DNA (mtDNA) mutations, ROS, oxidative stress, and mitochondrial processes such as fission, fusion, biogenesis, and turnover in the aging process. Additionally, I'll examine emerging research suggesting that an imbalance in mitochondrial fission and fusion, as well as degradation and biogenesis pathways, may contribute to various age-related disorders. Therapies aimed at ameliorating mitochondrial dysfunction by focusing on mitochondrial dynamics, quality control, and stress response-mediated mitohormesis pathways could potentially promote healthy aging, protect against age-related diseases, and improve longevity.

Age-related diseases that can be caused by mitochondrial dysfunction

Alzheimer's disease:

Alzheimer's disease is a neurodegenerative disorder that causes progressive memory loss and cognitive decline. Mitochondrial dysfunction has been linked to the development of Alzheimer's disease, and it is thought to play a role in the accumulation of amyloid plaques and tau tangles in the brain.

Parkinson's disease:

Parkinson's disease is a neurodegenerative disorder that causes tremors, rigidity, and slowness of movement. Mitochondrial dysfunction has been linked to the development of Parkinson's disease, and it is thought to play a role in the loss of dopamine-producing neurons in the brain.

Huntington's disease:

Huntington's disease is a genetic neurodegenerative disorder that causes involuntary movements, cognitive decline, and psychiatric symptoms. Mitochondrial dysfunction has been linked to the development of Huntington's disease, and it is thought to play a role in the death of neurons in the brain.

Diabetes:

Diabetes is a chronic disease that affects the way the body metabolizes sugar. Mitochondrial dysfunction has been linked to the development of diabetes, and it is thought to play a role in the impaired insulin secretion and insulin resistance that are characteristic of the disease.

Heart disease:

Heart disease is a group of diseases that affect the heart. Mitochondrial dysfunction has been linked to the development of heart disease, and it is thought to play a role in the inflammation and oxidative stress that are associated with the disease.

Stroke:

A stroke is a sudden loss of brain function caused by a disruption of blood flow to the brain. Mitochondrial dysfunction has been linked to the development of stroke, and it is thought to play a role in the cell death that occurs after a stroke.

Cancer:

Cancer is a group of diseases characterized by the uncontrolled growth of cells. Mitochondrial dysfunction has been linked to the development of cancer, and it is thought to play a role in the mutations and cell death that are associated with the disease.

How can we prevent Mitochondrial Dysfunction?

Mitochondrial dysfunction refers to the impaired functioning of mitochondria, the powerhouses of our cells responsible for producing energy. It can contribute to various health issues and accelerate the aging process. There are several approaches you can take to support mitochondrial health and potentially minimize dysfunction.

Balanced Diet: Consuming a well-balanced diet rich in whole foods, including fruits, vegetables, lean proteins, whole grains, and healthy fats, can provide essential nutrients needed for optimal mitochondrial function. Antioxidant-rich foods, such as berries, leafy greens, and nuts, can help protect mitochondria from oxidative stress.

Exercise Regularly: Engaging in regular physical activity, including both aerobic exercises and strength training, has been shown to promote mitochondrial health. Exercise stimulates the production of new mitochondria and enhances their function.

Stress Management: Chronic stress can negatively impact mitochondrial function. Engaging in stress-reducing activities such as meditation, deep breathing exercises, yoga, or spending time in nature can help promote a healthier mitochondrial environment.

Caloric Restriction: Some research suggests that caloric restriction or intermittent fasting may enhance mitochondrial function and promote longevity. However, it is important to approach these practices with caution and seek guidance from a healthcare professional, especially if you have underlying health conditions.

Maintain a Healthy Weight: Obesity and excess body fat can contribute to mitochondrial dysfunction. By maintaining a healthy weight through a combination of a balanced diet and regular exercise, you can support mitochondrial health and overall well-being.

Nutritional Supplements: Alongside a balanced diet, certain supplements may support mitochondrial health. Coenzyme Q10 (CoQ10), alpha-lipoic acid (ALA), and N-acetyl cysteine (NAC) are commonly recommended to support mitochondrial function and combat oxidative stress. Supplements such as Resveratrol, and CA-AKG, can help you in your wellness journey by improving Mitochondrial Function.

Reference:

The Role Of Mitochondrial And Metabolic Dysfunction in Ageing And Age-Related Diseases.