Mitochondria are double membrane structures known as mitochondria that produce >80% of cell energy through aerobic respiration. Furthermore, mitochondria regulate intracellular debris accumulation such as oxidative damage, protein aggregates and lipofuscin that fuels an endless cycle of danger response activation, inflammation and aging [3].
Scientists have recently developed a means of reversing this process using signals passed between mitochondria – commonly referred to as the powerhouses of cells – using signals passed between mitochondria. According to research in worms, fixing these cellular walkie-talkies extended their lifespans significantly.
Calorie Restriction
Caloric restriction (CR) is the classic experimental manipulation for slowing aging and increasing mitochondrial DNA telomere length in laboratory rodents and other animals, as well as decreasing ROS production and damage in postmitotic cells of these species. Such parameters have also been observed among long-lived species; yet its exact causes remain unknown.
Studies conducted over the last several years indicate that 40% CR can significantly decrease ROS generation and oxidative stress in rat organs, as well as increase maximum longevity by approximately 40%. These results support the free radical theory of aging, according to which reactive oxygen species produced within mitochondria is one of the primary contributors to cell aging.
Current studies are still unclear as to which dietary components cause the increase in mitochondrial function and decrease in oxidative damage seen with CR, though several theories have been proposed. It could be increased respiration, PNC1 activation in mitochondria, or deprivation leading to mitochondrial biogenesis increases. Studies with yeast indicate sirtuins may play an integral part of this longevity pathway – SIR2 being responsible for initiating increased respiration while SIRT3, 4, 5 mediate responses upon this increased respiration; Resveratrol can increase activity within these sirtuins significantly.
Reduced oxidative stress may be attributable to decreased production of reactive oxygen species by mitochondria and an increase in their ability to restore ATP damaged by oxidation. Or perhaps it could be related to an increase in endogenous tissue antioxidants produced during CR.
Mitochondria are major sites for oxidative damage to cell structures. Oxidative damage to mitochondrial DNA, proteins, and lipids occurs through electron transport chains in complexes I and III. Studies have revealed that CR can decrease rates of mitochondrial DNA-derived oxidative damage as well as accumulate accumulation; this result supports the mitochondrial free radical theory of aging.
Exercise
While mitochondria are widely seen as the powerhouses of cells, their role goes well beyond energy production alone. Mitochondria are responsible for many other processes within cells – from apoptosis and protein homeostasis regulation, to handling calcium (Ca2+). With age and physical inactivity come gradual impairments to mitochondria of skeletal muscles which leads to less energy being produced and an overall decline in muscle mass called “sarcopenia.”
Studies have repeatedly shown the benefits of endurance exercise and spontaneous physical activity for older adults in preventing sarcopenia and increasing quality skeletal muscle mitochondria in older adults, although its precise mechanisms remain unknown. Proposed explanations include mitochondrial biogenesis, dynamics (fusion/fission), autophagy/mitophagy or mitophagy as possible causal agents of these effects.
As we age, mitochondria become less effective at producing ATP due to oxidative stress and loss of structural integrity, leading to reduced production of the energy-storing compound ATP. This leads to mitochondrial DNA mutations and eventual limit in biogenesis; additionally, accumulation of mitochondrial proteins leads to advanced glycation end products such as lipofuscin formation that cannot be recycled through normal mechanisms for quality control; this further perpetuates damage, oxidative stress, and cell death in an endless cycle.
Studies have demonstrated the beneficial effects of regular exercise for improving skeletal muscle mitochondria quality and increasing expression of genes associated with mitochondrial biogenesis. Exercise was found to stimulate formation of new mitochondria by inhibiting their degradation; and resistance training significantly increases both mtDNA content and gene expression levels in aged muscles – with PGC-1a activation and Tfam activation linked with this increase; depending on duration and intensity of training [177].
As people age, their mitochondria and ribosomes’ ability to synthesize proteins reduces, leading to reduced muscle growth. Exercise can boost ribosomes and mitochondria in muscles to increase protein synthesis while slowing muscle atrophy. A diet rich in coenzyme Q10, alpha lipoic acid and acetyl L-carnitine can support mitochondrial functions and lower oxidative stress.
Supplements
Daily damage to mitochondrial DNA appears to be one of the driving factors in aging. If detected early enough, however, this damage can be reversed. Coenzyme Q10, or CoQ10 for short, serves as the body’s natural mitochondrial defense but levels gradually diminish with age. Shilajit and its metabolite PQQ work synergistically to protect mitochondria from further damage while replenishing CoQ10 levels; they also activate production of new mitochondria cells.
Mitochondria are the powerhouses of cells. Over time however, their production can become compromised, leading to age-related illnesses like Alzheimer’s, Parkinson’s, cardiovascular disease and diabetes. Furthermore, due to having small genomes themselves they are susceptible to mutations and errors leading to increased oxidative stress as well as epigenetic modifications resulting in further damage to tissues.
Rajagopal Viswanath Sekhar’s lab has revealed that it is possible to reverse these changes by increasing mitochondrial energy and improving function of mitochondria-encoded genes, among other methods. Experiments conducted in his lab demonstrate this fact and may extend mice lifespans significantly.
Atkins found that mice with genetic mutations that reduce SIRT1 (a gene responsible for mitochondrial activity) lived shorter lives; this could be reversed by adding back naturally occurring enzyme sirtuin 4. Sirtuin 4 increases levels of NAD+ (nicotinamide adenine dinucleotide), an energy producing molecule. According to studies on rats, Sirtuin 4 also slows down aging processes.
Restoring mitochondrial energy and slowing aging through nutritional supplements that mimic calorie restriction is another method for rejuvenation, with NAD+ precursors (nicotinamide adenine mononucleotide and nicotinamide riboside being two examples) providing additional cellular NAD+ levels and thus improving mitochondrial energy production, combatting oxidative stress, muscle function and neuroprotection, while simultaneously improving insulin sensitivity and regularizing blood lipids levels.
Researchers used urolithin A as a patented substance to enhance mitophagy – the process by which mitochondria recycle damaged ones – thereby stimulating an energy producing ATP energy source for use by cells. Urolithin A supplementation improved or extended life span in mice by 50%; they believe its effects may also benefit humans.
Diet
An effective mitochondrial diet can improve health, increase energy and prolong lifespan. To do this, it’s crucial that we consume ample nutrition while cutting back on foods known to exacerbate mito disease symptoms like inflammation. A healthy diet should include whole grains, nuts, seeds, legumes, fish, seafood and avocado as well as cooking oils such as olive, ghee coconut MCT or grass-fed butter in our diets.
A ketogenic diet (KD) helps the body shift away from using glucose as fuel and toward using fat instead as an energy source in its mitochondria, potentially slowing brain degeneration and improving overall cellular health – as evidenced by its ability to extend lifespan in mice carrying missense mutations of Med30 gene.
Diet is also essential in protecting mitochondria. Antioxidant rich fruits and vegetables such as vitamin C, carotenoids like lycopene and lutein as well as anthocyanins all help shield mitochondria. Eating legumes and nuts may also increase levels of niacin which is essential for healthy mitochondria.
Mitochondrial dysfunction is one of the major contributors to aging, due to free-radical damage. CoQ10 and PQQ coenzymes produced by our bodies can protect us from this damage; however, their concentration declines with age which causes symptoms associated with mitochondrial damage to worsen over time. However, studies have demonstrated that early stage mitochondrial damage may be reversed by using these coenzymes, suggesting an effective therapeutic approach against mitochondrial diseases such as cancer.
Other factors that can have an adverse impact on mitochondria are exposure to toxins, high blood sugar levels, lack of exercise, chronic inflammation and genetics. You have some control over some of these factors such as avoiding toxic materials and eating healthy diet. Strength training may also support your mitochondria by increasing ATP production within muscle cells.
Supplementing a nutritious diet with supplements like nicotinamide adenine dinucleotide (NAD), alpha lipoic acid (ALA), ubiquinol, coenzyme Q10 and resveratrol can further support mitochondria. Functional medicine labs such as the Advanced Oxidative Stress test or comprehensive metabolic panel may also assist in creating personalized plans to promote mitochondrial health; such tests measure glutathione markers and other indicators of oxidative stress and inflammation.