Mitochondrial decline is one of the most important hallmarks of the biological ageing process — as we age, the number of functional mitochondria in our cells decreases, the mitochondrial DNA accumulates mutations, the electron transport chain becomes less efficient, and the capacity to generate ATP declines. This mitochondrial dysfunction is one of the primary drivers of the age-related decline in the metabolic rate, in the cognitive function, in the muscle strength, in the cardiac function, and in the immune function that are the characteristic features of the ageing process. The PGC-1alpha (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) is the master regulator of mitochondrial biogenesis — it is the transcription factor that activates the programme of mitochondrial gene expression that results in the synthesis of new mitochondria and in the restoration of the mitochondrial population to a youthful level of function. Mitolyn is a supplement that was formulated to activate the PGC-1alpha pathway and to restore the mitochondrial function in ageing cells, combining seven superingredients that target each of the major mechanisms of mitochondrial decline.
The PGC-1alpha Pathway and Mitochondrial Biogenesis
The PGC-1alpha is a transcriptional coactivator that is activated by the AMPK enzyme (which is the cellular energy sensor that is activated when ATP levels fall) and by the SIRT1 enzyme (which is the NAD+-dependent deacetylase that is activated when the NAD+/NADH ratio rises, as it does during fasting and during exercise). When PGC-1alpha is activated, it translocates to the nucleus and coactivates the transcription factors that drive the mitochondrial biogenesis programme — including NRF-1 (nuclear respiratory factor 1), NRF-2 (nuclear respiratory factor 2), and the ERRalpha (estrogen-related receptor alpha). These transcription factors activate the expression of the nuclear-encoded mitochondrial genes (including the subunits of the electron transport chain, the enzymes of the TCA cycle, and the proteins of the mitochondrial import machinery), and together they drive the synthesis of new mitochondria and the restoration of the mitochondrial population. The activation of the PGC-1alpha pathway is therefore one of the most important therapeutic targets for the reversal of the mitochondrial dysfunction that underlies the ageing process.
The resveratrol is one of the most powerful natural activators of the PGC-1alpha pathway — it activates the SIRT1 enzyme (which deacetylates and activates PGC-1alpha) and thereby stimulates the mitochondrial biogenesis in muscle cells, liver cells, and neuronal cells. Multiple clinical trials have demonstrated that resveratrol supplementation improves the mitochondrial function, increases the exercise capacity, reduces the fasting blood glucose, and improves the cognitive function in older adults — the proposed mechanism involves the SIRT1-mediated activation of PGC-1alpha and the resulting stimulation of the mitochondrial biogenesis programme. The clinical trials of resveratrol have also shown that it reduces the markers of systemic inflammation (including CRP, IL-6, and TNF-alpha) and that it improves the cardiovascular function (including the endothelial function and the arterial compliance), which are the primary drivers of the cardiovascular disease and the cognitive decline that are associated with the ageing process.
The PQQ and the Mitochondrial Population Expansion Mechanism
Pyrroloquinoline quinone (PQQ) is a unique redox cofactor that is found in most plant-based foods and that has been shown in multiple studies to stimulate the mitochondrial biogenesis through a PGC-1alpha-independent mechanism that involves the activation of the cAMP response element-binding protein (CREB) and the upregulation of the mitochondrial translation machinery. PQQ is different from the other mitochondrial support ingredients in that it does not merely protect the existing mitochondrial population from damage — it actively stimulates the proliferation of new mitochondria, expanding the mitochondrial population in a way that the other mitochondrial support ingredients cannot achieve. The clinical studies of PQQ supplementation have shown that it improves the cognitive function, reduces the fatigue, and enhances the mitochondrial energy production in older adults — these effects are consistent with the hypothesis that PQQ stimulates mitochondrial biogenesis and thereby restores the mitochondrial energy capacity of the ageing cells.
Real-World Results and Who Should Use Mitolyn
Mitolyn is designed for adults who experience the common symptoms of mitochondrial decline — including the persistent fatigue that is not relieved by rest, the cognitive fog and the difficulty concentrating, the reduced exercise tolerance, the muscle weakness and the difficulty building muscle mass, and the metabolic dysfunction (weight gain, insulin resistance, elevated blood glucose) that are the hallmarks of the age-related metabolic decline. It is also appropriate for people who want a proactive approach to the prevention of the age-related diseases that are driven by mitochondrial dysfunction — including the neurodegenerative diseases (Alzheimer disease, Parkinson disease), the cardiovascular diseases (heart failure, atherosclerosis), and the metabolic diseases (type 2 diabetes, metabolic syndrome). Mitolyn is not intended for people who are pregnant or breastfeeding, for people with a known mitochondrial disease (such as MELAS or Leber hereditary optic neuropathy), or for people who are taking immunosuppressive medications after an organ transplant.
Practical Application
The recommended dose of Mitolyn is two capsules taken daily with a meal, which provides the equivalent of 250mg of resveratrol (as the trans-resveratrol form from Polygonum cuspidatum, which is the most extensively studied and the most potent form), 20mg of PQQ (as pyrroloquinoline quinone disodium salt), 500mg of alpha-lipoic acid (as the R-ALA form, which is the natural and more potent enantiomer), 300mg of acetyl-L-carnitine, 200mg of CoQ10 (as the ubiquinol form, which is the reduced and more bioavailable form), 100mg of n-acetylcysteine (NAC), and 50mg of magnesium (as magnesium citrate). For best results, Mitolyn should be taken consistently for at least 12-16 weeks, as the restoration of the mitochondrial population and the improvement in the mitochondrial function take time to develop and to become clinically evident. Mitolyn pairs well with the regular aerobic and resistance exercise programme (which activates the AMPK-PGC-1alpha pathway and stimulates the mitochondrial biogenesis), with the time-restricted eating pattern (which raises the NAD+/NADH ratio and activates the SIRT1-PGC-1alpha pathway), and with the cold exposure (which activates the PGC-1alpha pathway through the adrenergic stimulation of the brown adipose tissue).
Leave a Reply