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AMPK & Nrf2

AMPK or AMP-activated protein kinase is a cellular pathway that regulates metabolism and the use of stored energy. In longevity, AMPK activation supports metabolic wellbeing, including healthy blood sugar levels, inflammatory balance, body composition, and fat burning.

 

Nrf2 or nuclear factor erythroid 2-related factor, is a transcription factor that acts as a “switch,” activating genes that increase the production of protective antioxidants like glutathione. In longevity, Nrf2 upregulation blocks many pro-inflammatory factors and supports cellular detoxification.

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AMPK & Healthy Aging

Adenosine monophosphate-activated protein kinase, or AMPK for short, is a master regulator of longevity. It acts as a “sensor,” detecting when cellular energy levels, in the form of ATP, are low.

 

Upon detecting low ATP levels, AMPK upregulates cellular processes that make energy, including the breakdown of sugars and stored fats. It is also intrinsically involved in inflammation regulation. 

 

Fasting is a potent activator of AMPK because it decreases available energy. Conversely, energy “excess” from too much calorie intake and too little physical activity “turns off” AMPK. (1)

Research indicates that AMPK activation unlocks key longevity pathways here’s how:

 

Inhibits mTOR: mTOR is another sensor that coordinates cell growth when nutrients are abundant. When mTOR is chronically rather than normally activated cells may grow uninhibited and metabolic functions may dysregulate. When active, AMPK opposes or inhibits mTOR, helping to regulate cell growth and metabolism while also activating autophagy, a crucial cellular “housekeeping” system involved in longevity.

 

Promotes autophagy: Through the coordinated action of multiple proteins, AMPK promotes autophagy, the process by which cells cleanse themselves of old, damaged components. This low-energy state ultimately fuels the biosynthesis of new cellular components.

 

Generates mitochondria and supports mitochondrial energy production: Mitochondria, the body’s cellular energy powerhouses, impact multiple aspects of aging. Mitochondrial activity declines with age, but AMPK activation can counteract this decline by triggering mitochondrial biogenesis or the production of new, healthy mitochondria. Having greater numbers of healthy mitochondria as we age may protect against age-associated declines such as cognitive dysfunction.

 

Regulates glucose: AMPK impacts glucose uptake, breakdown, and synthesis.

 

Nrf2 and Aging:

 

Nuclear factor erythroid 2-related factor, or Nrf2 for short, is a transcription factor – a protein that helps turn genes “on” or “off” by binding to sections of DNA. In particular, it regulates the expression of antioxidant proteins, protecting the body against oxidative stress.

 

Oxidative stress is defined as an imbalance between levels of damaging reactive oxygen species or free radicals and the body’s ability to detoxify them or repair the resulting damage created by them. This damage occurs at a cellular and DNA level with far-reaching effects on the body. Oxidative stress can be caused by environmental toxins, such as mercury and BPA, and by natural processes such as UV light exposure and the aging process itself.

 

As a result, excessive DNA damage, without sufficient repair mechanisms, and depletion of intracellular glutathione, our body’s master protective antioxidant, has shown to be an age-accelerator. (2, 3

 

As we get older, our bodies’ Nrf2 activity declines, rendering us more susceptible to oxidative stress. (4

Interestingly, AMPK and Nrf2 appear to engage in cross-talk during the aging process. In fact, the activation of Nrf2 by several plant compounds, including berberine and quercetin, appears to be AMPK-dependent. (5,6) Conversely, when Nrf2 is inactivated, the health effects of AMPK-supporting phytochemicals are blunted.

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