Dr Thanh-Tam Pham - 09/11/2022

Mitochondria are often referred to be the powerhouse of the cell. They are present in nearly all types of human cells and are vital for our survival. 

The origin of mitochondria:

Mitochondria were once free-living organisms that used aerobic respiration. Larger anaerobic cells simply engulfed these aerobic mitochondria to use their energy giving rise to complex cells we find today in our bodies.

Mitochondria were likely evolved from an alphaproteobacteria that was engulfed by a eukaryotic cell between 1.5 billion and 2 billion years ago. The bacteria then formed an endosymbiotic relationship with the host and gradually developed into a mitochondrion.

Mitochondria have their own set of DNA (mtDNA) that is similar to bacterial DNA. During reproduction, half of the child’s DNA come from the father and half from the mother. However, the child always receives the mtDNA from the mother. MtDNA analyses have concluded that humans may have originated in Africa around 200,000 years ago, descended from a common ancestor known as mitochondrial Eve. 


Mitochondrial functions:

1. Production of energy:

Mitochondria help to turn the energy from food into energy that the cell can use in the form of ATP (Adenosine Triphosphate), the energy currency of the cell through a series of chemical reaction known as the citric acid cycle or Krebs cycle.

Mitochondria are found in all body cells that need energy. Each cell contains hundreds to thousands of mitochondria in their cytoplasm except for red blood cells that have no mitochondria.

2. Cell death or apoptosis:

This is an essential part of life. As cells become old or broken, they are cleared away and destroyed. Mitochondria help to decide which cells are destroyed by releasing Cytochrome C. In certain diseases such as cancer, there is a breakdown of normal apoptosis, so mitochondria are thought to play a role in cancer development.

3. Storing Calcium:

Calcium is vital for several cellular processes and mitochondria play a part by quickly absorbing calcium ions and holding them until they are needed. Calcium is necessary for muscle function, fertilisation, blood clotting, regulating cellular metabolism, steroid synthesis, and hormone signalling. 

4. Heat production:

Mitochondria can generate heat known as non-shivering thermogenesis. Brown fat has a lot of mitochondria. 

Mitochondrial dysfunction and fatigue:

Mitochondrial dysfunction is directly related to excessive fatigue, loss of overall energy and inability to perform simple tasks without exertion. Although mild fatigue can be caused by depression and other psychological conditions, moderate to severe fatigue involves cellular energy systems, loss of mitochondrial function and reduce ATP production as a result of aging and chronic diseases, oxidative damage to mitochondrial membranes and impaired mitochondrial function.

Mitochondrial dysfunction and chronic diseases:

Mitochondria damage is implicated as a major contributor for several chronic diseases such as cardiovascular disease, cancer, obesity, insulin resistance and type2 diabetes, neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Multiple Sclerosis, neurodevelopmental disease like autism, and Schizophrenia. 

Mutations in mitochondria DNA have been reported in different human diseases affecting organs and tissues. MtDNA is less protected than nuclear DNA from damage and mutagenesis and is especially susceptible to oxidative damage.

Mitochondria and Aging:

Research aimed at understanding the mechanism of cellular aging. All species have the common cycle of birth, growth, aging and death and they are born with a set of genes, but the expression of genes is usually influenced by environmental factors, which can result in the alteration of the rate of absolute growth, aging and death. Environmental factors not only affect the gene transcription, the gene translation, and the modification of proteins. Cellular functions depend on the ability to synthesize proteins with specific functions.

Mitochondria have long been identified as key biological players in aging. As they become increasingly dysfunctional over time, many age-related conditions such as Alzheimer’s, diabetes and cancer gradually set in.

Over recent years, researchers have investigated a link between mitochondrial dysfunction and aging. The theory is that reactive oxygen species (ROS) are produced in mitochondria as a by product of energy production and these highly charged particles can damage DNA, proteins. In aged subjects, mitochondria have impaired functions with decreased ATP production, significant increase ROS and diminished antioxidant defence. Mitochondria biogenesis declines with age due to alterations on mitochondrial dynamics and inhibition of mitophagy, an autophagy process that removes dysfunctional mitochondria.

Researchers have generally been sceptical of the idea that aging can be reversed, mainly due to prevailing theory that age-related diseases are the results of mutations in mitochondrial DNA and mutations cannot be reversed. 

However, implementation of strategies such as caloric restriction and regular physical training may delay mitochondrial aging.

Countermeasures for Aging:  Aerobic and resistance exercise augments muscle protein synthesis and mitochondrial biogenesis. Maintaining voluntary physical activities will partly prevent the age-related decline in muscle mitochondrial and contractile functions. Moreover, physical activities delay or prevent insulin resistance.

Long term aerobic exercise largely prevents age-related declines in mitochondrial DNA, their abundance, and functions in humans. Endurance training increases mitochondrial function, stimulates spontaneous physical activity and is a viable approach to interrupt the vicious cycle of aging.

Mitochondrial health is more related to physical exercise than just the age per se.

Obesity and physical inactivity are powerful drivers of the decline in mitochondria. Exercise has much more profound effects on mitochondria in skeletal muscles than weight loss by calorie restriction. 


Communication breakdown:

Mitochondria live inside our cells and have their own small genomes. There are molecular events that enable the communication inside the cells between the nucleus and mitochondria. As communication breaks down, aging accelerates. Dr David Sinclair, Harvard Medical School Professor of Genetics, said: “The aging process we discovered is like a married couple. When they are young, they communicate well but over time, living in close quarters for many years, communication breaks down.” Cells stay healthy as long there is efficient communication between the nuclear and mitochondrial genomes. It was found that NAD is a key molecule that shuttles information and co-ordinates activities between the cell’s nuclear genome and mitochondrial DNA. 

Aging might be reversible:

According to Dr David Sinclair, aging might be reversible by fixing the miscommunication in the cells with increasing NAD. “And just like with a couple, restoration of communication solved the problem”. 

Injecting NMN (Nicotinamide mononucleotide) in mice to increase NAD could reverse aging as studied by Sinclair and his group.  More research needs to be done in humans. 

The anti-aging supplements of Dr David Sinclair:

- NMN (Nicotinamide mononucleotide)

- Resveratrol

- Senolytics: Quercetin, fisetin

- Metformin 

- Vitamin D3

- Vitamin K2