If you were to discover the key to reversing or preventing disease processes, slowing or even stopping cellular changes associated with aging, as well as optimizing metabolism and energy production what would you do? Would you hold this treasure for your own, possibly sharing this gift of knowledge only with a few closest to you? Would you make it open public knowledge, free for all who seek to achieve immortality? Or would you establish an enterprise to produce and distribute this priceless commodity to the few which could afford it? Needless to say, you would fast become a highly regarded as well as very wealthy individual if this was your desire.
Such queries of goal or purpose if given the key to eternal youth are, of course, only intended to provoke thought. Yet for many who seek to cure disease and optimize our time in our earthly bodies, this quest is the drive for continued research for the turnkey to solving an abundance of problems with a singly perfect solution.
Mitochondria, the Energy Powerhouse of the Cell
Mitochondria, in the simplest of analogies, are the energy-generating powerhouses found in each of our cells. More mitochondria, not surprisingly, are found in muscular tissue – skeletal and cardiac muscle being the highest – because in these locations we need continuous energy production as well as surges of energy on demand. The energy units they generate are known as ATP, short for adenosine triphosphate, which is essential to power the other processes and reactions in the cell. It “costs” ATP to make glucose, to move things in and out of the cell, to perform metabolic reactions, to maintain cellular structures, and for cellular movement. Our body adapts to higher energy, or ATP, demand from activities like exercise by producing more mitochondria in the cell, further enhancing capacity for when it is needed.1,2 A more in-depth, yet easily digestible, discussion of the mitochondria and their function can be found at the Nature Education website.
Dysfunction or damage to these mitochondrial units has been associated with a variety of disease processes: Alzheimer’s and Parkinson’s disease,3 amyotrophic lateral sclerosis (ALS),4 diabetes,5 cardiovascular disease,6 liver disease,7 and autism8 to name a few. Defective mitochondria even appear to be passed, generationally, from parents with type 2 diabetes to their offspring.9 Dysfunction may contribute to the etiology of the disease or may be secondary, but once a dysfunctional state exists it continues to promote further damage on a cellular and even systemic level.
But how do some people’s mitochondria get “broken,” while those of others, particularly top-notch athletes seemingly stay on track?
Oxidative Stress = Mitochondrial Damage
Oxidative stress is a primary factor which contributes to mitochondrial damage and dysfunction. When the delicate mitochondria are damaged, they are not able to maintain necessary electrical and chemical gradients which are necessary for the production of ATP. Free radicals, also known as reactive oxygen species (ROS) and reactive nitrogen species (RNS) are inherently present in our body, but when they exceed the ability of our body to neutralize them, the create damage. Similar to our mitochondrial powerhouse analogy, ROS and RNS look like little fireballs that bounce around creating damage and more ROS until they are neutralized by the transfer of an electron. The mitochondria also produce ROS and RNS in the process of doing their cellular jobs as well.10,11
Although a certain amount of oxidative stress is necessary for biological processes and cellular signaling, when excessive amounts of oxidative stress occurs it causes damage.12 Contributors to increased oxidative stress in the body include heavy metals, pesticides and herbicides, air pollution, mold toxins, chronic infections, and even stress and insomnia.13,14 With chronic oxidative stress in excess of what our body has the means to neutralize, our main intracellular antioxidant glutathione, as well as many others, become depleted.15,16 Genetically, some individuals may be more susceptible to disease associated when they experience these additional stressors, however they are something we all have to deal with.
The loss of mitochondrial function comes back to another topic also mentioned in passing – it is a major contributor to the changes we associate with aging.17
Mitochondrial Repair and Optimization
Even within our mitochondria there are systems to deal with the oxidative species which are a byproduct of their function. Vitamin E and coenzyme Q10 (CoQ10) are two antioxidants which are important for mitochondrial function, repair, and biogenesis. Vitamin E is found in the mitochondrial membranes, and serves to protect them from lipid peroxidation.18 CoQ10 is crucial for the process of ATP generation in the mitochondria, as well as quenching the oxidative species. CoQ10 is synthesized in our body, however levels of this protective and energy-supportive antioxidant have been shown to decrease with age.19,20,21 Statin medications also have the effect of inhibiting our body’s synthesis of CoQ10.22 Dietary supplementation of vitamin E and CoQ10 has been shown to improve tissue and mitochondrial levels, while supplementation of CoQ10 also has the effect of sparing or partially restoring levels of vitamin E.23 CoQ10 has been shown to preserve mitochondrial function and ATP generation, even increasing their number, when subject to excessive oxidative stress.24
Resveratrol, one of the most well-known polyphenols which we find in red wine, comes from the skins of grapes as well as blueberries and raspberries. It has been studied for its potential health benefits as an antioxidant as well as for anti-aging effects.25,26 One of the mechanisms by which resveratrol may have positive impacts on health is by supporting mitochondrial function. Resveratrol has been shown to improve the mitochondrial function in liver and skeletal muscle cells, as well as to induce the formation of new mitochondria in endothelial cells (specifically the aorta of mice with type 2 diabetes).27 In mice treated with resveratrol, their aerobic capacity was increased, and they were protected against diet-induced obesity and insulin resistance.28 Treatment with resveratrol had an effect similar to exercise on the formation of new mitochondria, although they had a synergistic effect when combined.29 Resveratrol also has been shown to have effects similar to calorie restriction, retarding some of the effects of aging.30 No wonder we get so excited about this wine-associated polyphenol, although the concentration in wine is far too low to achieve such benefits!
Pyrroloquinoline quinone (PQQ) is last but definitely not least on this list of mitochondrial boosting agents. PQQ has been shown to support antioxidant status by inducing Nrf2, the “switch” which turns on our endogenous antioxidant and antioxidant-supporting enzyme production (see DIM and Detoxification blog for more about Nrf2).31 PQQ functions as a cellular nutrient, supporting growth as well as protecting cells in conditions of stress.32 PQQ protects the mitochondria and preserves their function in settings of acute oxidative stress, reducing cellular death.33 It stimulates the production of new mitochondria, similar to resveratrol and CoQ10.34 In humans, consumption of PQQ was shown to enhance mitochondrial function, reducing inflammation as well.35
Advanced Delivery Formats Overcome Bioavailability Limitations
Advanced liposomal and nanoemulsified delivery systems offer unmatched bioavailability for both fat- and water-soluble ingredients. The tiny, nano-size particles are not broken down by the harsh acids of the digestive system as they enter circulation with rapid absorption immediately in the mouth. This enables direct delivery of bioavailable nutrients to the bloodstream and cells of the body. Liposomal and nanoemulsified delivery systems dramatically improve bioavailability of substances such as resveratrol and CoQ10 which otherwise have limited bioavailability.36,37 Phospholipids, specifically phosphatidylcholine, form the external sphere of the liposomal and nanoemulsified particles. These phospholipids are additionally utilized by the cell, and are important for mitochondrial membrane health and repair.38
The possibility of enhancing energy production, and reducing damage and cellular changes associated with aging continues to fuel research investigating the impact that improved mitochondrial function may have on our health overall. The disease implications are significant as well, particularly for neurodegenerative disease. Nutritional support with substances such as these, particularly CoQ10, has been a topic of considerable clinical research for this reason. The potential to more dramatically impact many disease conditions with advanced delivery of nutritional substances is equally exciting for medical practitioners and those who struggle with chronic health conditions. Quicksilver Scientific is an ally in your quest for improved health and longevity, supporting you to achieve your optimal genetic potential.
6 Marzetti E, Csiszar A, Dutta D, et al. Role of mitochondrial dysfunction and altered autophagy in cardiovascular aging and disease: from mechanisms to therapeutics. Am J Physiol Heart Circ Physiol. 2013 Aug 15;305(4):H459-76. View Full Paper
7 Mantena SK, King AL, Andringa KK, et al. Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases. Free Radic Biol Med. 2008 Apr 1;44(7):1259-72. View Full Paper
21 Niklowitz P1, Onur S2, Fischer A, et al. Coenzyme Q10 serum concentration and redox status in European adults: influence of age, sex, and lipoprotein concentration. J Clin Biochem Nutr. 2016 May;58(3):240-5. View Full Paper
24 Noh YH, Kim KY, Shim MS, Choi SH, et al. Inhibition of oxidative stress by coenzyme Q10 increases mitochondrial mass and improves bioenergetic function in optic nerve head astrocytes. Cell Death Dis. 2013 Oct 3;4:e820. View Full Paper
28 Lagouge M, Argmann C, Gerhart-Hines Z, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127: 1109–1122, 2006. View Abstract
31 Zhang Q, Ding M, Gao XR, Ding F. Pyrroloquinoline quinone rescues hippocampal neurons from glutamate-induced cell death through activation of Nrf2 and up-regulation of antioxidant genes. Genet Mol Res. 2012 Aug 16;11(3):2652-64. View Abstract
33 Tao R, Karliner JS, Simonis U, et al. Pyrroloquinoline quinone preserves mitochondrial function and prevents oxidative injury in adult rat cardiac myocytes. Biochem Biophys Res Commun. 2007 Nov 16;363(2):257-62. View Full Paper
34 Chowanadisai W, Bauerly KA, Tchaparian E, et al. Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression. J Biol Chem. 2010 Jan 1;285(1):142-52. View Full Paper
35 Harris CB, Chowanadisai W, Mishchuk DO, et al. Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects. J Nutr Biochem. 2013 Dec;24(12):2076-84. View Abstract