Mitochondria
Episodes
Dr. Rhonda Patrick discusses GLP-1 agonists, alpha-lipoic acid, ubiquinone vs. ubiquinol, calcium needs, and liquid biopsy cancer screening.
Dr. Rhonda Patrick explores blood tests to track health, statin alternatives, mitochondrial supplements, and vitamin B12 and autism risk in her latest Q&A.
In the clip, Dr. Gibala discusses high-intensity interval training's future, stressing translating research into public health applications.
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Dr. Rhonda Patrick discusses GLP-1 agonists, alpha-lipoic acid, ubiquinone vs. ubiquinol, calcium needs, and liquid biopsy cancer screening.
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Rhonda Diet Omega-3 Pregnancy Mitochondria Vitamin B12 Muscle Sauna Cardiovascular Blood Test Red Light TherapyDr. Rhonda Patrick explores blood tests to track health, statin alternatives, mitochondrial supplements, and vitamin B12 and autism risk in her latest Q&A.
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In the clip, Dr. Gibala discusses high-intensity interval training's future, stressing translating research into public health applications.
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In this clip, Dr. Martin Gibala outlines the relationship between exercise types, mitochondrial growth, and their combined effect on fat metabolism.
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In this clip, Dr. Martin Gibala explains VO2 max's role in health and how non-athletes can optimize workouts to boost their cardiorespiratory fitness.
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Dr. Martin Gibala discusses HIIT's health benefits and describes common HIIT protocols.
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In this clip, Dr. Chris McGlory explains the potential mechanisms by which omega-3s impact muscle mass and function.
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In this clip, Dr. Mark Mattson describes the importance of incorporating rest, recovery, and refeeding into one's routine.
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In this clip, Dr. Satchin Panda explains the rationale behind the metabolic benefits associated with time-restricted eating.
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Metformin blunts exercise-induced gains in muscle, strength, and aerobic fitness | Rhonda Patrick ClipIn this clip, Dr. Rhonda Patrick describes the many open questions that remain regarding the interaction between metformin and exercise at the molecular level.
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In this clip, Tim Ferriss and Dr. Rhonda Patrick discuss acute versus chronic inflammation and how supplemental antioxidants can negate some of the benefits of exercise.
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Bioenergetic superiority of ketones and their role in reducing oxidative stress | Dominic D'Agostino ClipIn this clip, Dr. Dominic D'Agostino explains the interrelationship between ketones and lactate as sources of energy for the brain and the role ketones may have in reducing oxidative stress through greater energetic efficiency.
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In this clip, Dr. David Sinclair identifies some of the practical considerations of resveratrol supplementation and discusses his personal use of the compound.
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Nicotinamide Riboside vs. Nicotinamide Mononucleotide - dosing and effects on NAD+ | David Sinclair ClipIn this clip, Dr. David Sinclair discusses the current state of research on the NAD+ boosters nicotinamide riboside and nicotinamide mononucleotide.
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In this clip, Dr. David Sinclair describes the role of NAD+ in the regulation of the body's circadian clock and sirtuin production.
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Mitophagy: a signal for mitochondrial biogenesis, metabolic adaptation, and cellular differentiation ClipDr. Guido Kroemer describes mitophagy, a cellular signal for mitochondrial biogenesis, and a key player in other physiological processes.
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How the cell prioritizes and targets organelles and protein aggregates for degradation by autophagy ClipDr. Guido Kroemer describes the cellular process of autophagy and what factors trigger its activation.
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Fasting associated with sickness behavior critical to surviving bacterial infection | Guido Kroemer ClipDr. Guido Kroemer describes how fasting associated with sickness behavior is critical to surviving infection.
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Dr. Guido Kroemer describes the spectacular biological phenomenon known as autophagy.
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Dr. Satchin Panda describes the beneficial effects of time-restricted feeding in mice in terms of mitochondrial health.
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Dr. Eric M. Verdin discusses the roles of the ketogenic diet, beta-hydroxybutyrate, HDAC inhibitors, NAD+, and more in the context of aging.
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Dr. Judith Campisi discusses the role of cellular senescence in the aging process and the development of cancer.
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Nutrition Vitamin D Metabolism Diabetes Telomeres Omega-3 Inflammation Depression DNA Damage Stem Cells Micronutrients Mitochondria Autophagy Autism Schizophrenia Resveratrol Sulforaphane Insulin Blue LightDr. Rhonda Patrick makes her fifth appearance on the Joe Rogan Experience.
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Ketosis Nutrition Brain Alzheimer's Diet Microbiome Performance Insulin Resistance Mitochondria Dementia Insulin SupplementsDr. Dominic D'Agostino discusses the health benefits associated with a modified Atkins diet, ketosis, and supplemental ketones.
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Dr. George Brooks discusses the metabolic pathway known as the “lactate shuttle" and its role in the recovery from traumatic brain injury.
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Nutrition Brain Diet Epigenetics Cholesterol Omega-3 Inflammation Micronutrients Multiple Sclerosis Mitochondria Vitamin K Antioxidant AutoimmunityDr. Terry Wahls discusses the nutrition protocol she used to reverse her secondary-progressive multiple sclerosis.
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Dr. Patrick describes how magnesium, an essential mineral that ~56% of the US population is deficient in, can help you maximize your mitochondria to increase oxidative capacity and, potentially, enhance exercise performance.
Topic Pages
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Autophagy
Damaged mitochondria are selectively engulfed by autophagosomes via PINK1-Parkin–driven ubiquitination, culminating in lysosomal degradation.
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Cold exposure
Cold exposure triggers β-adrenergic signaling that enhances mitochondrial biogenesis and UCP1-mediated uncoupling in brown adipose thermogenesis.
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Hallmarks of aging
Accumulating mitochondrial DNA mutations elevate ROS and energy deficits, mechanistically propagating genomic instability, proteostatic stress and cellular senescence.
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NAD+
Within mitochondria, NAD+ accepts TCA-cycle electrons forming NADH, which complex I oxidizes, regenerating NAD+ and driving ATP synthesis.
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Nicotinamide mononucleotide
Nicotinamide mononucleotide is intracellularly converted to NAD+, fueling mitochondrial dehydrogenases and sirtuin-mediated oxidative phosphorylation.
News & Publications
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Aging impairs mitochondrial function, disrupting the heart’s energy supply. Over time, this energy shortfall undermines cardiac cell function, driving the heart’s gradual decline. A recent study found that supplemental urolithin A—a bioactive compound derived from pomegranates and walnuts—boosts mitochondrial health and reduces pro-inflammatory lipids called ceramides, ultimately enhancing cardiac function.
Researchers investigated the effects of supplemental urolithin A in models of natural aging in mice and heart failure in rats and assessed its effects on plasma ceramide levels in healthy older adults. Mice received 50 milligrams per kilogram of urolithin A daily (in food) for eight weeks, rats received 50 milligrams per milliliter (in water) for 24 hours following a simulated heart attack, and the older adults took 1 gram of urolithin A (via supplement) or a placebo daily for two to four months.
Supplemental urolithin A improved systolic and diastolic cardiac function in models of natural aging and heart failure—an effect of the restoration of mitochondrial structure and enhanced mitophagy at the cellular level. Four months of urolithin A supplementation in healthy older adults significantly lowered plasma ceramides.
Ceramides are a class of bioactive lipids that contribute to cardiovascular disease by promoting inflammation, insulin resistance, and lipid accumulation in arteries. Elevated ceramide levels are linked to a higher risk of atherosclerosis and adverse cardiac events.
Urolithin A is a byproduct of gut microbial metabolism of ellagic acid, a bioactive compound found in pomegranates and walnuts. The capacity to form urolithin A from ellagic acid varies considerably from person to person (depending on gut microbial composition) and decreases with age. Pterostilbene, a compound found in blueberries and some supplements, boosts urolithin A conversion. Learn more in this clip featuring Dr. Rhonda Patrick.
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Urolithin A, a compound derived from pomegranates and walnuts, boosts mitophagy and enhances cognitive function in aged mice. neurosciencenews.com
Mitochondrial function declines with aging, driving many age-related conditions, including Alzheimer’s disease. A recent study in mice found that urolithin A, a compound derived from pomegranates and walnuts, promotes mitophagy – the targeted destruction of damaged mitochondria – in the brain.
Researchers fed older mice urolithin A (200 milligrams per kilogram of body weight) daily for five months. They subjected the animals to various learning and memory tests, assessed their sense of smell, and examined their brains.
They found that urolithin A markedly improved the animals' learning, memory, and sense of smell, enhanced memory-related brain functions, and reduced the accumulation of amyloid-beta and tau protein (hallmarks of Alzheimer’s disease). Urolithin A also improved the function of lysosomes, cellular structures that play a crucial role in mitophagy, by breaking down and recycling damaged mitochondria.
These findings suggest that urolithin A boosts mitophagy in mice, improving brain health and cognitive function. Urolithin A is a byproduct of gut microbial metabolism of ellagic acid, a bioactive compound found in pomegranates and walnuts. The capacity to form urolithin A from ellagic acid varies considerably from person to person (depending on gut microbial composition) and decreases with age.
Due to the low quantities of ellagic acid in foods and the poor conversion rate, achieving a human dose comparable to that used in this study likely would require supplemental intake. Nevertheless, the findings align with other evidence suggesting that long-term dietary intake of foods containing ellagic acid benefits cognitive health.
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High-dose statin impairs mitochondrial energy output by more than 30 percent in adults with overweight. pubmed.ncbi.nlm.nih.gov
Statins comprise a large class of drugs that lower blood cholesterol levels by blocking the production of an enzyme involved in cholesterol synthesis. Although statins are generally well tolerated, as many as 10 to 20 percent of people taking the drugs experience complications, including myopathy (muscle damage), liver damage, and cognitive problems. A recent study found that atorvastatin, a commonly prescribed statin, reduces muscle cells' energy production.
The study involved eight inactive but otherwise healthy adults with overweight who took a high dose of atorvastatin (80 milligrams) daily for 56 days. Researchers collected muscle samples from the participants before they took the statin and then again after 14, 28, and 56 days to assess their muscle cells' capacity for energy production.
They found that over the 56 days, the muscle cells' ability to produce energy via oxidative phosphorylation diminished by more than 30 percent. Additionally, the muscle’s capacity to use oxygen, a key indicator of cardiorespiratory fitness, dropped by as much as 45 percent. The study investigators attributed this decline to the statin’s inhibition of specific components (complexes III and IV) within the mitochondria that are vital for energy production.
The findings from this very small study shed light on how high-dose atorvastatin therapy can significantly reduce the energy production in muscle cells, driving a decrease in muscle and aerobic fitness. They also underscore the importance of further research in larger groups to balance the health benefits of statins with their potential effects on muscle function. Learn more about statins in this deep-dive discussion with Dr. Peter Attia.
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Epicatechin-rich cocoa boosts endogenous antioxidant production and mitochondrial function while protecting against muscle damage in people with peripheral artery disease. pubmed.ncbi.nlm.nih.gov
Peripheral artery disease affects roughly 230 million people worldwide and arises when plaque accumulation in the arteries impairs the delivery of oxygen-rich blood to the muscles, causing pain with physical activity. A recent study found that cocoa flavanols promote the production of endogenous antioxidants and proteins involved in mitochondrial function in people with peripheral artery disease.
The study involved 16 people with peripheral artery disease who were enrolled in COCOA-PAD, a six-month randomized controlled trial in which participants who received a cocoa beverage containing 15 grams of cocoa (providing 75 milligrams of epicatechin, a flavanol compound) daily showed marked improvements in walking performance and less pain with activity. Researchers examined muscle samples taken before and after the trial to study changes in muscle fibers, endogenous antioxidants (heme oxygenase-1 and NAD(P)H dehydrogenase [quinone] 1), and energy-related proteins.
They found that participants who received the cocoa beverage had higher levels of endogenous antioxidants, correlating with less muscle damage. They also had higher levels of UQCRC2, a protein critical for energy production in the mitochondria.
These findings suggest that cocoa flavanols promote the synthesis of endogenous antioxidants and proteins involved in energy production and point toward a mechanism for the beneficial effects observed in COCOA-PAD. Because heme oxygenase-1 and NAD(P)H dehydrogenase [quinone] 1 are targets of nuclear factor erythroid 2-related factor 2 (Nrf2), the investigators posited that the mechanism driving the beneficial effects of cocoa flavanol supplementation is Nrf2 activation.
Nrf2 is a protein typically found in the cytoplasm of mammalian cells. Nrf2 can relocate to the nucleus, where it regulates the expression of hundreds of antioxidant and stress response proteins that protect against oxidative damage triggered by injury and inflammation. Although this study found that cocoa induces Nrf2, one of the most robust inducers of Nrf2 is sulforaphane, a compound derived from broccoli. Learn more about sulforaphane and Nrf2 in this clip featuring Dr. Jed Fahey.
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Obesity triggers mitochondrial fragmentation, hindering fat-burning efforts. www.sciencedaily.com
Obesity, which affects more than 40 percent of U.S. adults, arises when the body stores excess fat, primarily in adipose tissue. While adipose tissue is an important source of energy, its capacity to produce energy in the setting of obesity diminishes, complicating weight loss efforts. A recent study demonstrates that obesity promotes fragmentation of the mitochondria in adipose cells, resulting in smaller and less effective mitochondria with reduced fat-burning capacity.
Researchers fed mice an obesogenic diet and assessed its effects on their fat cells' mitochondrial function. Then, they analyzed gene activity in fat samples collected from people with obesity.
They found that after eating a high-fat diet, mitochondria in the animals' adipose cells underwent fragmentation, forming smaller, less efficient mitochondria with diminished fat-burning capabilities. This metabolic alteration was orchestrated by the activity of RaIA, a molecule that serves various roles, one of which involves assisting in the breakdown of dysfunctional mitochondria. Deleting this gene in the mice prevented excessive weight gain despite consuming an obesogenic diet, highlighting RaIA’s crucial role in transitioning from a healthy weight to obesity. They also found evidence of increased gene activity in people with obesity that corresponded with persistent elevation in RalA.
These findings suggest that obesity induces fragmentation of mitochondria, compromising their function and driving a vicious cycle of diminished fat-burning capability and increased body fat gain. Evidence suggests cold exposure and fasting promote weight loss. Learn more in this episode featuring Dr. Ray Cronise.
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Alzheimer’s disease affects more than 24 million people worldwide, with numbers expected to grow as the population ages. A growing body of evidence links mitochondrial dysfunction and oxidative stress to the development of Alzheimer’s disease. A recent study in mice found that sulforaphane, a bioactive compound derived from broccoli and broccoli sprouts, boosts memory, improves mitochondrial function, and reduces oxidative stress.
Researchers studied normal mice and mice prone to developing a condition similar to Alzheimer’s. They fed half of each type of mice standard mouse chow. They fed the other half normal chow supplemented with a broccoli sprout powder rich in glucoraphanin and myrosinase – the precursors to sulforaphane. They subjected the mice to various memory tests and assessed their mitochondrial function.
They found that Alzheimer’s disease-prone mice that ate the broccoli sprout powder-supplemented chow performed better on memory tests than those that didn’t. These mice demonstrated higher levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α) and mitochondrial transcription factor A – proteins that regulate mitochondrial biogenesis (the production of new mitochondria). They also showed upregulated expression of cellular antioxidant defense system components that protect against oxidative stress.
These findings suggest that sulforaphane from broccoli sprouts prevents age-related cognitive decline by maintaining mitochondrial function, thereby reducing oxidative stress in mice.
Sulforaphane is an isothiocyanate compound with robust antioxidant, anti-inflammatory, and anti-cancer effects. It reduces oxidative stress by switching on the activity of Nrf2, a cellular protein that activates the transcription of cytoprotective proteins that protect against oxidative stress due to injury and inflammation. Sulforaphane is the most potent naturally occurring inducer of Nrf2. Learn how to grow your own broccoli sprouts – a terrific source of sulforaphane – in this short video.
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Spermidine supplementation revitalizes fertility and mitochondrial health in aging mice. medicalxpress.com
Female fertility decreases considerably with age, with nearly 87 percent of women over the age of 45 unable to conceive. However, some evidence suggests that dietary components can preserve fertility. A recent study in mice shows that spermidine, a molecule found in many common foods, including legumes, nuts, and cheese, improves fertility and egg quality.
Researchers analyzed the ovarian metabolic profiles of young and old mice. Then, they supplemented the aged mice with spermidine and assessed its effects on ovarian function.
They found that ovarian spermidine levels in older mice were notably lower than in younger mice, correlating with decreased oocyte (egg cell) quality and other indications of ovarian aging. However, administering spermidine to the older mice enhanced follicle development, oocyte maturation, and early embryonic development, thereby boosting the animals' overall fertility. They also found that the older mice exhibited impaired ovarian mitophagy, but spermidine restored it.
Mitophagy, a form of autophagy, is the selective degradation of mitochondria. It helps ensure that the body’s cells are metabolically efficient, ultimately serving as a trigger for mitochondrial biogenesis, the process of producing new mitochondria. Failures in mitophagy are associated with several chronic diseases, including cardiovascular disease, kidney disease, and Alzheimer’s disease. Learn more about mitophagy and autophagy in our overview article.
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Research identifies a possible ceiling for the mitochondrial benefits of intense exercise. www.sciencedirect.com
Mitochondrial function and whole-body maximal oxygen uptake – a surrogate measure of metabolic function and health – are closely linked. Exercise boosts mitochondrial function, but some evidence suggests there is an upper limit to exercise’s benefits. A new study demonstrates that the benefits of exercise on mitochondrial function peak, after which the benefits plateau or even drop.
The study involved 11 healthy adults enrolled in a four-week high-intensity interval training (HIIT) program. The exercise load and duration gradually increased over the first three weeks of training (scaling up to 154 minutes per week) and then decreased for the final week to allow recovery. Researchers measured the participants' glucose tolerance and collected muscle biopsies throughout the intervention. They also assessed continuous blood glucose profiles in world-class endurance athletes.
They found that after the week with the highest exercise load, the participants' mitochondrial function had declined markedly, impairing their glucose tolerance and insulin secretion. Interestingly, the impaired mitochondrial function coincided with the loss of cellular Nrf2, a protein involved in the body’s antioxidant defense response. In addition, they found that the endurance athletes had worse glucose control than a matched control group.
The findings from this small study suggest an upper limit to the mitochondrial benefits of HIIT exists, potentially impeding performance and harming health. However, it’s noteworthy that the participants tolerated 90 minutes of HIIT per week and didn’t experience impairments until reaching 152 minutes. One of the unique advantages of HIIT is that a shorter routine can have robust beneficial effects comparable to those of endurance training. Learn more about HIIT in this episode featuring Dr. Martin Gibala.
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High-intensity exercise mitigates sleep-induced metabolic disruptions, offering a potential defense against type 2 diabetes. www.sciencedirect.com
Poor sleep negatively affects metabolism, impairing glucose tolerance and increasing the risk of developing type 2 diabetes. Findings from a recent study indicate that HIIT compensates for the harmful effects of sleep loss on glucose tolerance.
Researchers assigned 24 healthy young men to one of three five-night sleep protocols: normal sleep (eight hours nightly), sleep restriction (four hours nightly), and sleep restriction with HIIT. Researchers collected muscle biopsies to assess muscle protein synthesis before and after the intervention.
They found that the group with sleep restriction experienced marked reductions in glucose tolerance, mitochondrial respiratory function, and sarcoplasmic protein synthesis. They also experienced altered diurnal skin temperature rhythms. However, sleep-restricted participants who engaged in HIIT did not experience these disturbances.
The sarcoplasm is the cytoplasm of muscle cells. Sarcoplasmic protein synthesis is crucial for muscle growth, repair, and maintenance, contributing to overall muscle health and function.
This study was small, but the findings suggest that sleep restriction impairs metabolic function, circadian rhythmicity, and muscle protein synthesis. However, engaging in HIIT during periods of sleep restriction helps counter these effects. Learn more about the benefits of HIIT in this episode featuring Dr. Martin Gibala.
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Chronic alcohol consumption impairs mitochondrial function in heart cells, increasing cardiovascular risks. onlinelibrary.wiley.com
Alcohol has profound, adverse effects on the human body, compromising liver function and cognitive performance and increasing the risk for various cancers. A recent study demonstrates that alcohol impairs mitochondrial function and cellular metabolism and increases inflammation in heart cells.
Researchers grew human-induced pluripotent stem cells into three-dimensional heart cell structures called cardiac spheroids and exposed them to clinically relevant amounts of ethanol (the type of alcohol found in alcoholic beverages) for five weeks. They then examined various aspects of the heart cells, including mitochondrial function, gene expression patterns, and metabolite production.
They found that prolonged ethanol exposure reduced the heart cells' mitochondrial function, increased reliance on glycolysis (a less efficient energy production process), hindered fatty acid breakdown, and impaired cardiac structure development. The cells exhibited changes in gene expression related to metabolic processes, heart development, and responses to hypoxia. They also produced more inflammation-associated metabolites.
Chronic alcohol consumption increases the risk for various heart-related issues, including arrhythmias (irregular heartbeats), cardiomyopathy (heart muscle disease), and heart failure. In addition, chronic heavy alcohol use has adverse effects on bone health, increasing the risk of fractures during weight-bearing activities.
These findings highlight the harmful effects of chronic alcohol consumption on heart cells at the molecular level. Avoiding alcohol can be challenging, but vigorous aerobic exercise can help reduce alcohol cravings. Learn more in this video featuring Dr. Rhonda Patrick.
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Regular exercise reprograms bone marrow macrophages, inducing lasting mitochondrial changes that accumulate, driving a tempered inflammatory response. www.sciencedaily.com
Although inflammation is a critical component of the body’s immune response, excess inflammation drives many chronic diseases, such as autoimmune disorders, cardiovascular diseases, diabetes, and cancer. A new study in mice shows that regular exercise reprograms macrophages, altering how they sense and respond to pathogens and reducing inflammation.
Macrophages are immune cells that participate in pathogen elimination via phagocytosis. Distinguished by their polarization, “M1” macrophages exhibit a proinflammatory phenotype, while “M2” macrophages exhibit an anti-inflammatory phenotype. A high M1 to M2 ratio indicates inflammation and a chronic disease state.
Researchers collected macrophages from the bone marrow of two groups of mice – one that had exercised regularly for eight weeks and one that had been sedentary. Then they exposed the macrophages to lipopolysaccharide (a bacterial toxin that induces an acute inflammatory reaction) and assessed the cells' responses.
They found that macrophages from the exercised mice exhibited decreased activation of NF-κB, the primary transcription factor of M1 macrophages. The macrophages also demonstrated reduced expression of inflammation-related genes, increased expression of M2 macrophage-associated genes, and improved mitochondrial function.
These findings suggest that regular exercise modulates macrophages' responses to inflammation by enhancing their respiratory capacity and altering gene expression, with potential implications for preventing or treating inflammatory diseases. Read more about the benefits of exercise in our overview article.
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Taurine supplementation extends life by 12 percent in animal studies, pointing to a potentially promising anti-aging strategy that may highlight the r www.cuimc.columbia.edu
Taurine is an amino acid that participates in immune health and neurological function. Findings from a recent study suggest that taurine influences longevity. Mice that received supplemental taurine lived as much as 12 percent longer than those that didn’t.
Researchers conducted a multi-part experiment in several species. First, they measured blood taurine concentrations in mice, monkeys, and humans at different ages and found that taurine decreased in all three species over time. Notably, taurine concentrations were 80 percent lower in older adult humans than in young children.
Then they gave middle-aged mice either taurine (1,000 milligrams per kilogram of body weight) or an inactive substance once daily until their natural deaths. Among mice that received taurine, median lifespan increased by 10 to 12 percent, roughly equivalent to about eight years in humans. They repeated their experiment in monkeys, worms, and yeast and observed similar effects. They also found that taurine reduced several hallmarks of aging in all the species studied, including cellular senescence, mitochondrial dysfunction, DNA damage, and inflammation.
Finally, they measured blood taurine concentrations in humans following an acute bout of exercise. They found that exercise increased the levels of taurine metabolites in the blood, providing a potential mechanism for the anti-aging effects of exercise.
These findings suggest that supplemental taurine reverses age-related taurine declines and extends both healthspan and lifespan in several species. Learn about other nutrients that influence aging in this episode featuring longevity expert Dr. Bruce Ames.
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Circadian desynchrony negatively affected rat Leydig cell function and thus testosterone production. (2022) www.nature.com
From the publication:
CD [circadian desynchrony] was characterized by changed and decreased rhythmic locomotor activity and reduced blood testosterone. In the Leydig cells changed transcription of the clock genes (Bmal1, Clock, Cry1 and Reverba/b increased while Per1/2 reversed phase) was detected. This was followed by reduced transcription of genes (Star, Cyp11a1, and Hsd3b1/2) primarily involved in mitosteroidogenesis. In parallel, mitochondrial membrane potential (Δψi) and ATP production declined losing their characteristic oscillatory pattern. Also, the main markers of mitochondrial biogenesis (Ppargc1a, Nrf1, Tfam, Cytc), fusion (Mfn2), and mitophagy (Pink1 and Tfeb) were disturbed. Collectively, CD [circadian desynchrony] targets mitochondria in Leydig cells by reducing mitosteroidogenesis, mitoenergetics, and disturbing mitochondrial dynamics. These changes contribute to testosterone decline compromising androgen-dependent functions, including reproduction.
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New insights on how some individuals with obesity can lose weight medicalxpress.com
Exercise boosts mitochondrial function and promotes weight loss among people who struggle to lose weight with dieting alone.
Most weight loss programs focus on reducing caloric intake. Although this strategy works for many people, a subset of people with obesity are diet-resistant – failing to lose weight even when adhering to a low-calorie diet. Findings from a new study suggest that exercise promotes weight loss in diet-resistant women by boosting mitochondrial function.
Mitochondria are tiny cellular organelles that produce energy in the presence of oxygen. They are often referred to as the “powerhouses of the cell” because of their role in the production of ATP. Mitochondrial dysfunction, the disruption of normal mitochondrial function that occurs over time, is a driver of many chronic diseases, such as cancer, type 2 diabetes, and cardiovascular disease, and is a hallmark of aging.
The investigators enrolled 20 women with obesity for the study. Half of the women had exhibited diet resistance when following a 900-calorie-per-day diet, while the other half had exhibited diet sensitivity. Both groups participated in a supervised, six-week exercise program that included both aerobic and resistance exercises, performed three times per week. The investigators assessed the women’s body composition and metabolic markers and collected muscle tissue samples for biopsy.
They found that at the end of the six-week exercise program, the women who were diet resistant exhibited improved body composition and muscle metabolism and increased numbers of muscle mitochondria. The exercise program elicited only minimal effects in women who were diet sensitive. Interestingly, the diet-sensitive women exhibited risk factors associated with metabolic syndrome, suggesting that diet-sensitive obesity confers a greater risk for cardiometabolic disease.
These findings demonstrate that exercise promotes weight loss and metabolic health in women with obesity and diet resistance and may confer greater health benefits than rapid diet-induced weight loss. Learn more about the benefits of exercise in our overview article.
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Urolithin A, a compound derived from walnuts and pomegranates, restores aging muscles.
Mitochondria are the key organelles responsible for cellular energy production. Mitochondrial dysfunction, a hallmark of aging, occurs over time as reactive oxygen species damage vulnerable mitochondrial membranes and energy production becomes less efficient. A consequence of mitochondrial dysfunction is the loss of muscle mass and strength. Findings from a recent study suggest that urolithin A, a compound derived from walnuts and pomegranates, promotes mitophagy, increases muscle strength, and improves performance.
Urolithin A is a metabolic byproduct of ellagic acid, a bioactive compound found in walnuts and pomegranates. Bacteria in the human gut break down ellagic acid to produce urolithins. Scientists have identified about 20 urolithins, but the most studied of these is urolithin A, which exerts potent anti-cancer and anti-inflammatory properties.
Mitophagy is a type of autophagy, an intracellular program involved in the disassembly and recycling of unnecessary or dysfunctional cellular components, that selectively targets mitochondria. It helps ensure that the body’s cells are metabolically efficient and ultimately serves as a trigger for mitochondrial biogenesis, the process by which new mitochondria are produced. Failures in mitophagy are associated with several chronic diseases, including cardiovascular disease, kidney disease, and Alzheimer’s disease
The study involved 88 healthy adults (40 to 65 years old) who had overweight. The investigators randomly assigned two groups of the participants to receive either 500 or 1,000 milligrams of urolithin A daily for four months. Another group received a placebo. Before and after the intervention, the investigators measured the participants' muscle strength, aerobic endurance (VO2 max, peak oxygen consumption), physical performance, and markers of inflammation, mitochondrial function, and mitophagy.
They found that compared to participants who took the placebo, the participants who took the urolithin A supplement exhibited a roughly 12 percent increase in muscle strength following the intervention. The participants who took the urolithin A also showed improvements in aerobic endurance, physical performance, and mitochondrial function and had higher levels of proteins involved in mitophagy and mitochondrial metabolism in their muscle tissue.
These findings suggest that urolithin A increases muscle strength, improves performance, and promotes mitophagy and mitochondrial function. Walnuts are excellent sources of urolithin A. See the story below to read about how eating walnuts reduces the risk of premature death and promotes longevity.
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A mitochondrial link to depression: master regulator of mitochondrial biogenesis PGC-1 alpha protects mice from stress-induced depression www.sciencedaily.com
From the article:
It was known that the protein PGC-1a1 (pronounced PGC-1alpha1) increases in skeletal muscle with exercise, and mediates the beneficial muscle conditioning in connection with physical activity. In this study researchers used a genetically modified mouse with high levels of PGC-1a1 in skeletal muscle that shows many characteristics of well-trained muscles (even without exercising).
These mice, and normal control mice, were exposed to a stressful environment, such as loud noises, flashing lights and reversed circadian rhythm at irregular intervals. After five weeks of mild stress, normal mice had developed depressive behaviour, whereas the genetically modified mice (with well-trained muscle characteristics) had no depressive symptoms.
Eliminating the neurotoxic effects of kynurenine:
The researchers discovered that mice with higher levels of PGC-1a1 in muscle also had higher levels of enzymes called KAT. KATs convert a substance formed during stress (kynurenine) into kynurenic acid, a substance that is not able to pass from the blood to the brain. The exact function of kynurenine is not known, but high levels of kynurenine can be measured in patients with mental illness.
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Compound derived from walnuts and pomegranates may boost mitochondrial and muscle health. www.eurekalert.org
As a person ages, mitochondrial function declines, driving many age-related conditions, including the progressive loss of muscle mass and strength. Findings from a recent study suggest that a compound derived from ellagic acid metabolism helps restore mitochondrial and muscle health in older adults.
Ellagic acid is a bioactive compound found in a wide variety of fruits, nuts, and vegetables, especially walnuts, pomegranates, and rose hips. Bacteria in the human gut break down ellagic acid to produce compounds called urolithins. Scientists have identified about 20 urolithins, but the most studied of these is urolithin A, which exerts potent anticancer and anti-inflammatory properties. The capacity to form urolithin A from ellagic acid varies considerably from person to person and decreases with age.
The randomized clinical trial involved 66 older adults (average age, 71 years) who had poor mitochondrial function. Half of the participants received 1,000 milligrams of urolithin A daily for four months; the other half received a placebo. The participants underwent muscle endurance tests and a timed walking test at the beginning of the study and again at various timepoints throughout the study. Study investigators measured ATP production in the participants' muscle and acylcarnitines, ceramides, and C-reactive protein (markers of mitochondrial health and inflammation) in the participants' blood.
At the end of the four-month study, participants who received the urolithin A supplement showed marked improvements in muscle endurance compared to those who received the placebo. Those who received the urolithin A also exhibited decreased levels of acylcarnitines, ceramides, and C-reactive protein.
These findings suggest that urolithin A, a compound derived from ellagic acid, promotes mitochondrial health and improves muscle endurance in older adults. Ellagic acid is a type of polyphenol. Learn more about polyphenols in our overview article.
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Ubiquinol supplementation may protect bones and aid muscles during vigorous physical activity. pubmed.ncbi.nlm.nih.gov
Exercise has well-established health benefits, such as reducing the risk of cardiovascular disease and cancer. However, long term strenuous exercise can put stress on the bones. Findings from a recent study suggest that supplementation with ubiquinol during strenuous exercise provides benefits for bone health and energy metabolism.
Ubiquinol, a bioactive compound that exerts antioxidant properties, is the reduced form of coenzyme Q10. It is found in foods such as beef liver, tuna, and broccoli and is also available as a dietary supplement.
Previous research has demonstrated that ubiquinol positively affects performance during low-intensity physical activity. The current study investigated whether supplementation would affect performance and mitigate bone pathologies during vigorous exercise.
The randomized, double-blind placebo-controlled trial involved 100 healthy and well-trained male firefighters. The authors of the study provided participants with a daily supplement containing either 200 milligrams ubiquinol or a placebo for two weeks. The participants performed two bouts of vigorous exercise, separated by a 24-hour rest period, and provided blood samples before, during, and after the exercise sessions.
The blood samples revealed that supplementation increased biomarkers of bone formation, including parathyroid hormone and osteocalcin. The authors also observed increased levels of the transcription factor PGC-1α, and the hormones insulin, leptin, and noradrenaline, which they suggest may benefit skeletal muscle and mitochondrial function, providing a competitive advantage during training or recovery.
These findings suggest that ubiquinol supplementation can support bone formation and skeletal muscle function during high-intensity exercise.
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Stressed mitochondria leak DNA fragments that induce inflammation. www.sciencemagazinedigital.org
Oxidative stress drives many disease processes. In mitochondria, in particular, it promotes the release of mitochondrial DNA into surrounding cytosol where it can trigger cellular responses involved in autoimmunity.
A critical aspect of mitochondrial DNA release is the formation of pores created by the oligomerization of specific proteins called voltage-dependent anion channels (VDACs), which are found in the outer mitochondrial membrane. A new study in a mouse model of lupus suggests that inhibition of VDAC oligomerization blocks mitochondrial DNA release, preventing subsequent immune responses.
These findings suggest that inhibition of VDAC oligomerization may be an alternative therapeutic approach for a wide range of diseases likely associated with mitochondrial DNA release, such as lupus and Parkinson’s disease.
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Nutrient-induced Mitochondrial Activation (NiMA): A Novel Lysosome-to-Mitochondria Signaling Pathway Disrupted by Amyloid-β Oligomers papers.ssrn.com
The mechanisms of mitochondrial dysfunction in Alzheimer’s Disease (AD) are incompletely understood. We show that activation of lysosomal mechanistic target of rapamycin complex 1 (mTORC1) by insulin or amino acids stimulates mitochondrial activity and regulates mitochondrial DNA synthesis in neurons. Amyloid-β oligomers, which are precursors of amyloid plaques in AD brain and stimulate mTORC1 protein kinase activity at the plasma membrane, but not at lysosomes, block this nutrient-induced mitochondrial activity (NiMA) by a mechanism dependent on tau, which forms neurofibrillary tangles in AD brain. NiMA was also disrupted in fibroblasts derived from a patient with tuberous sclerosis complex, a genetic disorder that causes dysregulation of lysosomal mTORC1. Thus, lysosomal mTORC1 couples nutrient availability to mitochondrial activity, and links mitochondrial dysfunction to AD by a mechanism dependent on soluble building blocks of plaques and tangles. https://ssrn.com/abstract=3188445
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Pilot study finds supplementation with nicotinamide riboside improves blood pressure/arterial health particularly in individuals with hypertension. www.genengnews.com
A pilot study finds supplementation with nicotinamide riboside (500 mg, twice a day) improves blood pressure and arterial health particularly in individuals with mild hypertension (compared to placebo). The decrease in blood pressure could translate to a 25% reduction in heart attack risk.
The study also found that 1,000 mg daily of nicotinamide riboside boosted levels increased NAD+ by 60%.
Nicotinamide riboside is a form of vitamin B3 that is converted into NAD+. NAD+ is a cofactor for many metabolic enzymes and becomes depleted across various tissues as we age. This causes the mitochondria to suffer and mitochondrial decay is also thought to also be a key driver of aging.
To learn more about the role of nicotinamide riboside and NAD+ in aging…check out my conversation with Dr. Eric Verdin. Click on the timeline for the exact time point when we discuss nicotinamide riboside.
Dr. Eric Verdin Episode: https://www.foundmyfitness.com/episodes/eric-verdin
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Mitochondria Initiate and Regulate Sarcopenia journals.lww.com
Mitochondrial-regulated apoptosis provides a strong signaling network that contributes to sarcopenia (8). We have taken the perspective that both neural and muscle components contribute to muscle wasting, but mitochondrial health is central to initiating and perpetuating the signal for sarcopenia. We argue that mitochondrial dysfunction leads to increased mPTP opening and initiates apoptotic signaling in muscle cells and motor neurons. In aging, this is not corrected because mitophagy is inhibited. Proteasome activation leads to removal of cellular contents close to the site of dysfunctional mitochondria, and this cellular dismantling expands proportionally to the accumulation of dysfunctional mitochondria. Although aging induces widespread systemic mitochondrial dysfunction, perhaps as a result of high ROS or accumulation of mtDNA damage, we have considered that retrograde and anterograde communication likely exists between dying muscle and motor neurons, which may accelerate death in both compartments. Additional studies are needed to establish if exercise and nutrition can be used to effectively improve mitochondria health and reduce sarcopenia in aging populations. In our view, targeting dysfunctional mitochondria and increasing healthy mitochondria in motor neurons and muscle fibers provide the best strategy for reducing sarcopenia.