AMPK Pathway Copy

AMP-activated protein kinase, or AMPK, is known as a master regulator of metabolism. Cells activate AMPK when they are running low on energy, and AMPK is activated in tissues throughout the body following exercise or during calorie restriction.A growing body of evidence sug­gests that boosting AMPK activity can prevent and even reverse, the life-shortening effects of aging. Insufficient AMPK activity may be related to virtually all pathological aging processes. Research indicates that restoring AMPK not only increases longevity, but works to fight the symptoms of aging in individual body systems.

AMPK stands for adenosine monophosphate-activated protein kinase. It is found in every living cell of every living mammal (and most other animals) on Earth. If you want to avoid the life span-shortening symptoms of aging, you need to maintain optimal AMPK activity. AMPK has been referred to as a “metabolic master switch.” AMPK controls a gamut of metabolic pathways that enable us to extract energy from food, store and distribute that energy safely through the body, and ultimately use that energy for everything from moving and mating to talking and thinking, and even to understanding these very words as you read them. The core role of AMPK is to sense each cell’s energy status at every moment, and to trigger responses that maintain the cell’s energy at precisely the optimum level. Too little available energy starves the cell, while too much energy can exhaust and disrupt cellular components. In either case (too little or too much energy), the cell (and the tissues, organs, and systems in which it is a part) functions inefficiently. That energy inefficiency ultimately leads to the dysfunctions we identify as the diseases (or symptoms) of aging.

Here’s how AMPK works: Every cell in your body depends absolutely on a steady supply of energy in the form of chemical bonds. When you eat and absorb nutrients, energy from chemical bonds in food is released and passed down a complex series of enzymes until it is stored again in a molecule called adenosine triphosphate, or ATP. The more ATP that is present in the cell, the higher the cell’s available energy supply. When ATP is broken down to release energy for cellular work, a major end product is adenosine monophosphate, or AMP. If a cell were to use up all of its energy from ATP, it would rapidly fill up with low-energy AMP molecules. It would then run out of energy, and shortly thereafter, it would collapse and die, unable to sustain even the simplest energy-requiring processes. And that is precisely where AMPK comes into play. AMPK is biochemically activated in the presence of rising levels of AMP (and decreasing levels of ATP). Activated AMPK, in turn, increases fatty acid oxidation and glucose transport, thereby releasing additional energy from available or stored sources (fats and sugars).

“Aging, the progressive accumulation of damage that occurs to an organism over time, eventually leads to disease and death. High blood glucose and insulin levels and the signaling pathways they regulate play critical roles in aging and age-related diseases. Turning down the activity of these pathways improves lifespan in multiple organisms”

Slow Aging With AMPK

  • Although we seem to age by losing function in each organ or organ system separately, the truth is that aging largely results from universal processes that are common to all cells in the body.
  • Management of energy from food to power cellular activity is one such process, and it is regulated by an enzyme called AMPK.
  • Activated AMPK promotes all the processes we look for to maintain a youthful profile: rapid, efficient release of energy, with little energy storage as fat or new sugar molecules.
  • Thus, activated AMPK keeps us lean and active, with a steady renewal of cellular components.
  • AMPK activity fades with age. Just as importantly, when excessive calories are available, the result is accelerated tissue aging.
  • You can boost AMPK activity through exercise and/or calorie restriction, but should also make use of natural supplements that support AMPK activity.
  • Boosting AMPK activity will keep your tissues young and slow aging throughout your body.

The net result of high AMPK is tight control over cellular energy levels so that they never fall low enough to impair cellular activity, but never rise high enough to damage cellular machinery. The benefit of such tight control of energy levels is evident from studies of fruit flies genetically modified to synthesize high levels of AMP: They live up to one-third longer as a result of precise energy maintenance by activated AMPK. A long life span would be predictable in cases of high activation of AMPK which promotes energy-releasing processes while suppressing energy-storing processes. As a result, organisms with high AMPK activity are vigorous, active, and lean, with relatively low blood sugar and fat levels and little fat storage, and a very low risk of heart disease, diabetes, and other metabolic disorders.

AMPK also promotes the cellular “housekeeping” function called autophagy, in which cells consume themselves and recycle their contents, a process that eliminates damaged DNA and misshapen proteins that can themselves impair cellular function and even trigger cancers. As a result, young organisms with higher AMPK activity have a very low risk of cancer and degenerative disorders, such as Alzheimer’s disease, which stem from misfolded or damaged proteins.

High levels of activated AMPK occur in youth, while low levels of activated AMPK occur in aging. We grow old, not simply because time passes, but because our youthful levels of AMPK drop away. And AMPK activity does decline sharply with age. That is why we become less energetic and get fatter as we grow older, while becoming increasingly vulnerable to cancer and diseases associated with impaired DNA and protein function. But the modern lifestyle, with its overabundance of processed foods and low level of physical activity, is even worse for the AMPK system than aging alone. It is now clear that, when caloric intake remains much higher than needed to sustain energy expenditure (think couch potato eating potato chips), AMPK activation is markedly decreased. With reduced AMPK activity, cells decrease their energy-releasing ATP-generating activities, and instead shift to energy-storing processes that generate new fat deposits and make excess new glucosemolecules. The modern picture of the overweight person, living a sedentary lifestyle and enjoying an overabundance of processed junk carbohydrates and calories, is harmful for AMPK activation and therefore deadly. We are literally eating ourselves to death. By suppressing AMPK activation, we develop dangerous fat deposits, especially in the belly region. Burgeoning fat masses reduce insulin sensitivity and produce systemwide inflammation, which may contribute to “metabolic syndrome.”4

Inflammation is intimately involved in many disorders of aging, such as cardiovascular disease, diabetes, and cancer, conversely, inflammation further suppresses AMPK activation in a rapidly tightening lethal spiral.

In fact, AMPK is so important in maintaining and restoring youthful function that it has been called a “gerosuppressor,” that is, a compound that significantly suppresses, not one or several diseases, but processes of biological aging. This is shown by the results of several lines of laboratory investigation. AMPK activation triggers increased production of mitochondria, the energy-releasing “power plants” found in every cell.4 Since a reduction in mitochondrial numbers and function is associated with accelerated aging, AMPK-induced “mitochondrial biogenesis” can be expected to slow the aging process. Activating AMPK in human cells in culture also stimulates production and activation of SIRT1, an enzyme that is increased in laboratory animals with extended life spans.SIRT1 can also be activated by marked calorie restriction, which has been demonstrated to increase life span in some species. Research now shows that AMPK activation can trigger the life-extending actions of SIRT1. Clinical Studies demonstrate that AMPK slows aging by modulating expression of critical transcription factors and enzymes, as would be expected by its effects on SIRT1. One specific area of genetic modulation by AMPK is in control of systemwide inflammation; studies show that AMPK inhibits signaling by the master inflammation regulator called NF-kappaB. Reducing inflammation throughout the body is a key target in extending life span by preventing premature death from complications of aging such as cardiovascular and metabolic diseases.

Some Natural ways to Activate AMPK:

  1. Exercise
  2. Calorie Restriction
  3. Gynostemma Herb
  4. Rosehips

Gynostemma pentaphyllum, a traditional Vietnamese herb, activates AMPK to dramatically reshape the way human bodies handle excess glucose and fat. A study of human type II diabetics, taking no medications, showed that daily supplementation with G. pentaphyllum tea for 12 weeks:1

  • Reduced fasting blood sugar levels by a significant 54.1 mg/dL, compared with just 10.8 mg/dL in the control group.
  • Lowered hemoglobin A1c levels, a measure of chronic glucose elevation, by a 2% unit reduction, which accounts for a 10-foldimprovement over controls.
  • Significantly reduced insulin resistance in the supplemented group, while insulin resistance rose in the control subjects.

Trans-tiliroside, a bioactive obtained from rose hips, adds additional AMPK activation to sharply curtail fat accumulation and speed fat burning. In cultured human fat cells (adipocytes), rose hip extract and trans-tiliroside both prevented new fat accumulation.1

In a study of obese humans, a daily drink made from rose hip powder, used for six weeks, resulted in:1

  • Reduction of systolic blood pressure by 3.4%.
  • Reductions in total and LDL (“bad”)cholesterol of 4.9 and 6%, respectively, and of 6.5% in the ratio of LDL to HDL (“good”) cholesterol.
  • 17% reduction in a standardized cardiovascular disease risk score.


To really understand aging, we have to recognize that it is not an automatic result of time passing, but rather the result of reversible events that occur in all cells, regardless of the tissue or organ system to which they belong. One of the most fundamental of those events is a decline in activity of AMPK, the universal cellular energy sensor that dictates whether cells store energy as dangerous fats or use energy efficiently to power vital processes. Activated AMPK creates a more youthful energy profile, one with only small amounts of fat stores, a great deal of energy for useful activity, and rapid recycling of old, damaged proteins. Studies are increasingly revealing the central role of AMPK in maintaining youthful function across the entire spectrum of cell and tissue types, resulting in increased longevity. This “systemic anti-aging” approach is likely to be much more successful than mainstream medicine’s “one disease at a time” strategy, which treats each disease as a separate entity and accounts for America’s destructive addiction to prescription drugs. It’s critical that you understand AMPK and how to optimize its activation in your body if you want to extend your life span in the best possible state of health.

Targeting the AMP-activated protein kinase for cancer prevention and therapy