Every cell contains hundreds of mitochondria, each with its own genome, mitochondrial DNA separate from that of the cell nucleus. The primary role of mitochondria is to generate chemical energy store molecules, adenosine triphosphate (ATP), used to power cell activities. Mitochondrial dysfunction with aging isn’t just a loss of ATP generation and production of a harmful amount of reactive oxygen species, however. It can also be connected with chronic inflammation, as mislocalization of mitochondrial DNA can trigger sensors of the innate immune system to provide inflammatory signaling.
A growing body of evidence implicates mitochondrial dysfunction as a common pathomechanism involved in many of the hallmark features of the AD brain, such as formation of amyloid-beta (Aβ) aggregates (amyloid plaques), neurofibrillary tangles, cholinergic system dysfunction, impaired synaptic transmission and plasticity, oxidative stress, and neuroinflammation, that lead to neurodegeneration and cognitive dysfunction. Indeed, mitochondrial dysfunction concomitant with progressive accumulation of mitochondrial Aβ is an early event in AD pathogenesis.
Among diverse factors that contribute to human aging, the mitochondrial dysfunction has emerged as one of the key hallmarks of aging process and is linked to the development of numerous age-related pathologies including metabolic syndrome, neurodegenerative disorders, cardiovascular diseases and cancer. Mitochondria are central in the regulation of energy and metabolic homeostasis, and harbor a complex quality control system that limits mitochondrial damage to ensure mitochondrial integrity and function.
When mitochondria become defective (and are not subject to mitophagy), mitocondrial DNA (mtDNA) can go on to trigger chronic inflammation. Turns out that niacin may cure mitochondrial myopathy as well as improve muscle strength and fatty liver and respiratory chain activity in humans.
Decline in both mitophagy and autophagy pathways are associated with aging and various age-related pathologies including neurodegenerative, cardiac and immune system disorders, hepatic dysfunction, kidney failure as well as cancer [10,158,159,160,161]. Defective mitophagy has been implicated in Parkinson’s disease [16], and high levels of mtDNA deletions have been reported in the substantia nigra neurons from aged humans and patients with Parkinson’s disease [40,162].
Mitochondrial function is dependent on a quality diet, such as the Mediterranean diet. A high-carb diet will lower the rate of adipose tissue mitochondrial respiration.
Pyrroloquinoline quinone (PQQ) protects mitochondrial function from free radical attack. PQQ protected cells from mitochondrial inhibition by rotenone, 3-nitropropionic acid, antimycin A, and sodium azide. The ability of PQQ to stimulate mitochondrial biogenesis accounts in part for action of this compound and suggests that PQQ may be beneficial in diseases associated with mitochondrial dysfunction.
In this study, 10 subjects (5 females, 5 males) ingested PQQ added to a fruit-flavored drink as a daily dose (0.3 mg PQQ/kg). PQQ supplementation resulted in significant decreases in the levels of plasma C-reactive protein, IL-6 and urinary methylated amines such as trimethylamine N-oxide, and changes in urinary metabolites consistent with enhanced mitochondria-related functions.
In this study of 23 males consuming 20 mg/day of PQQ, there was no significant difference in aerobic performance, but PQQ impacted mitochondrial biogenesis by way of significant elevations in PGC-1α protein content.
PQQ can significantly protect mice from exercise-induced fatigue and oxidative damage by improving mitochondrial function.
Intermittent fasting (being hungry) helps, as does not overeating starches and fats.
In diabetics, metformin improves mitochondrial function, restores the levels of ETC complexes, and enhances AMPK activation and mitophagy.
Piracetam enhances fluidity of brain mitochondrial membranes. Piracetam enhanced ATP production, and reduced sensitivity for apoptosis in a variety of cell and animal models for aging and Alzheimer disease.
The microbiome’s biochemical signals also regulate the growth and function of energy-producing mitochondria across many cell types, including those in fat, muscles, heart and the brain. When these cues are missing in ultraprocessed diets, mitochondria function less well, and their dysregulation has been linked to obesity, diabetes, Alzheimer’s disease, mood disorders and cancer.
Simple dietary measures such as reducing salt with or without restricting fructose can increase mtDNA and improve markers of oxidative stress. Dr. David Perlmutter (who, apparently, has access to this paywalled paper) points out here a 70-fold increase in mitochondria via reducing both salt and fructose.
Dr. Sreekumaran Nair at Mayo Clinic in Rochester, New York, did a unique study and published his results in March 2017. He had two groups involved; 1 group age 18-30, and another group 65-80. Both groups did HIIT (High-Intensity Interval Training) for 3 months. Cardiovascular and lung function improved 28% in the younger group and 17% in the older group. Here’s the unusual part. Muscle biopsies were done, showing actual metabolic, cellular changes in mitochondrial function. The older group had a 69% improvement in mitochondrial function. The younger group had a 49% improvement.
