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If one were to travel back in time to the 1800s, it would have been difficult to imagine that bacterial diseases would ever cease being the leading cause of suffering and death.1

Even highly educated doctors of the era would point out that no one knew what caused tuberculosis, cholera, diphtheria, and other infectious diseases. Educated skeptics could go further and state that assuming the cause of these plagues was someday discovered—could they ever be cured?

No one could have predicted what happened during the following 100 years. Bacteria would be proven to be the cause behind these epidemic killers and antibiotics were developed to cure most of them.

The 20th century was characterized by fantastic advances in life expectancy as factors behind human mortality shifted from bacterial infections to degenerative disease.2

You’re about to discover a novel method to circumvent a major underlying cause of obesity, age-related decline and cessation of life.

As 2015 approaches, we have a huge advantage over our ancestors who died of bacterial diseases. We already know many of the underlying causes of degenerative disease and are rapidly developing technologies to circumvent them.

In this special issue, we’re introducing you to an enzyme within our cells called AMPK. In youth, AMPK is more activated 3 and helps protect against obesity4 and diabetes.5

As we grow older, cellular AMPK activation decreases, weight gain often follows, and we are more likely to succumb to the destructive factors of aging.6-8

AMPK is found inside every cell and serves as your body’s “master regulating switch.” It determines body fat composition and how long you’ll live.

Unlike previous generations that wallowed in medical ignorance, documented methods exist right now to activate AMPK and in the process, reduce storage of body fat and protect against degenerative disorders that are today’s leading killers.

Scientists view the discovery of AMPK as a major advance in how we understand and combat aging. By reactivating cellular AMPK, we move tantalizingly closer to gaining meaningful control over deadly aging processes, such as excessive weight gain, that predispose us to so many degenerative disorders.

This article will explain the significance of AMPK in age-related disease and reveal several proven ways to enhance activation of this youth-promoting enzyme.

Why AMPK Levels Decline

Most humans today suffer chronic nutritional overload.9 When this happens, vital life functions may become disrupted, such as the proper uptake of glucose10 and fat11 from our blood for effective energy regulation.

In response to excess calorie consumption, cellular housekeeping decreases, resulting in the accumulation of cellular waste12 and damaged proteins.13 Abundant food intake impairs beneficial longevity genes while causing pro-inflammatory genes to become dominant.14

Just imagine what would happen if you never got out of bed and had all meals delivered to you. In the hospital setting, this lack of mobility increases mortality risk. Your cells are no different.

When cells are chronically over-nourished, the energy-mobilizing enzymatic activity of AMPK diminishes.15,16 The outward effects manifest in the form of unwanted weight gain, diabetes, degenerative disease, and premature death.

Few individuals are able to consistently under eat. Fortunately, scientists have identified a cellular enzyme called AMPK that, when activated, mimics many of the beneficial effects observed in calorie restrictors, including loss of surplus body fat.17

AMPK Promotes Longevity And Reduces Fat Storage


The science of bioenergetics is producing paradigm-shifting discoveries, including the role of AMPK in regulating the ways our bodies use and transform energy.
AMPK is the “switch” that is the link between metabolic disease, inflammation, and longevity. This “switch” tells our cells when to store and generate energy-containing molecules such as fat, and when to “hunker down” and use existing energy stores.
When switched “on,” AMPK triggers the use of stored energy from fats, enhances removal of fats and sugar from the blood, increases production of mitochondria, and reduces inflammation and cellular “junk.”
Calorie restriction and vigorous exercise activate AMPK, shrinking body fat stores (especially in the belly region), lowering blood sugar and lipid levels, and producing other beneficial effects that retard the aging process.
The drug metformin also activates AMPK, with similar body-wide results.
A pair of natural botanical extracts have now been found to activate AMPK, reducing belly fat, cholesterol, blood sugar, and insulin levels.
Instead of combating longevity threats using multiple drugs, supplementation with AMPK-activating botanicals can address these problems at its source.
Age-induced risk factors can be tackled efficiently by boosting AMPK activity with Gynostemma pentaphyllum and trans-tiliroside from rose hips.


Your Cells’ “Master Switch”

A large part of the reason you are alive at this moment is because of the enzymatic reactions18,19 occurring in the trillions of cells20 in your body.

Cells can be described as little bundles of biochemical reactions. Enzymes often make biochemical reactions in the cell possible. Vital life functions our cells perform are dependent on cellular enzyme activity.

Over the past 30 years, scientists have been investigating the properties of an enzyme called AMPK, which is a “ master switch”21 that, in many ways, controls how our cells behave.

Extensive research shows that by increasing AMPK activation, we can reduce many of the destructive factors of aging, thus enabling cells to return to their youthful vitality.

In preclinical research, enhanced AMPK activity has been associated with a 20-30% increase in life span,7,22,106 but that’s just the beginning of the health benefits conferred by this critical cellular enzyme.

Increased AMPK activation has been shown to help reduce fat storage (especially dangerous belly fat), increase insulin sensitivity (to lower blood glucose), reduce cholesterol/triglyceride production, and suppress chronic inflammation.7,23 All of these factors underlie the lethal diseases of aging.

In a study of obese individuals, subjects lost more than an inch in waist circumference and half an inch in hip circumference using an AMPK activity- boosting botanical extract.24

What Is AMPK?

AMPK is found in every cell in our body.23,25 It serves as the body’s “master regulating switch” that fends off degenerative factors by revitalizing aging cells.

AMPK is involved in reducing fat storage,26 regulating glucose uptake,27,28 creating new mitochondria,29 and eliminating cellular garbage that accumulates inside aging cells.30

The discovery of how AMPK regulates aging processes has been decades in the making. A PubMed search now delivers over7,500 published articles on various aspects of AMPK. For those who are curious, AMPK is the acronym to define the enzyme adenosine monophosphate-activated protein kinase.31

An important property of AMPK is that it induces multiple longevity factors, which have been shown to increase stress-resistance and extend life span in many organisms.32,33

One such longevity factor boosted by AMPK is the SIRT1 enzyme.7 SIRT1 operates by silencing genes that code for unhealthy responses to stress, including the inflammatory response,34,35 excess fat storage,36 and new fat production.33,37,38 SIRT1 activity is also increased by calorie restriction,39,40 the only fully proven way to increase life span in all animal models tested to date, further indicating the importance of AMPK in activating SIRT1.41,42

Resveratrol found in red wine helps activate SIRT1,43,44 but AMPK activates SIRT1 more directly.7,45,46
The Dangers Of Reduced AMPK

In many ways, AMPK acts as a traffic cop, efficiently moving excess fat and sugar into our cells to be burned for energy. When we are young, AMPK keeps our metabolic functions running smoothly. Ideally, we are slim and disease-free. But as we age, AMPK signaling declines, which may quickly lead to an excess buildup of blood glucose and dangerous fat accumulation.7 This turns into a lethal combination for many aging humans.

With reduced AMPK signaling, a range of damaging conditions begins to take over a previously healthy body, often leading to an early death. These damaging conditions include:

Increased belly fat,47,48
Chronic inflammation,7,47,48
Elevated blood sugar,47-50
Insulin resistance,7,47-50
High cholesterol and triglycerides,47,48
Decreased numbers and function of mitochondria,7,47,48
Increased accumulations of abnormal or damaged proteins in our cells that lead to neurodegeneration.7,51

Conventional medicine diagnoses and treats each of the above conditions as a separate disease requiring separate medications when, in fact, they are all associated with one source: declining AMPK activity.

Another deadly impact of reduced AMPK activation is a decreased number of functional mitochondria29,52 and the accumulation of cellular garbage,7,53,54 which eventually renders cells nonfunctional.51,55,56

As scientists continue to unravel the mystery of AMPK, they are discovering that many of the known biochemical longevity factors (such as SIRT1, FoxO, and p53) are activated by normal AMPK function.7 For example, p53 is a tumor-suppressing gene that inhibits uncontrolled cell propagation. Without AMPK, these longevity genes fail to perform their duties, potentially resulting in premature death.7,33

Fortunately, research demonstrates that when AMPK signaling is boosted, these deteriorating processes are reversed,57 restoring more youthful metabolism, preventing related chronic diseases, and potentially adding years of useful, productive life.

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Just before a major medical advance occurs, there is a rapid series of discoveries that radically alter the scientific landscape.

We are on the verge of such a tectonic change.

Doctors may soon recommend that virtually all patients boost a cellular enzyme in order to delay and reverse pathological aging.

We expect this anti-aging approach will become as common as a doctor washing his hands between patients...in other words universally accepted.
UCLA Biologists Corroborate This Anti-Aging Strategy

Before we could even finish this issue, biologists at UCLA published the results of a study showing that when AMPK is activated in one part of an organism, there is a systemic slowing of aging throughout the entire body, including the brain.

They showed that AMPK activation enables cells to discard old/damaged cellular components through a process called “autophagy.” By getting rid of this “cellular garbage” before it destroys cells, autophagy protects against aging.

Activated AMPK facilitates the efficient removal of cellular debris that scientists believe is an underlying cause of neurodegenerative and other age-related diseases.

The most exciting finding of this study was that in response to activating AMPK in only one organ of fruit flies, life span increased by 30%!

We’ve long encouraged Life Extension members to take steps to systemically activate AMPK. The incredible news is that there’s finally an effective means for everyone to induce these robust age-reversal benefits in their own body.

Anti-Aging Benefit Of Metformin Now Available To All

Metformin may be the most effective compound humans can take today to combat degenerative disease. Its primary mechanism is to activate AMPK!

We recommended metformin over 20 years ago based on findings that it might reverse certain aging processes. Metformin was approved in England as a diabetes treatment in 1958. The FDA did not approve it until 1994. The death toll caused by the regulatory delay in approving metformin is incalculable.

Life Extension has published dozens of articles showing that metformin may prevent and treat certain cancers, in addition to helping reverse insulin resistance and excess belly fat. While a number of our members have obtained a metformin prescription, most can’t gain access to it because their doctor won’t prescribe it for anything except type II diabetes.

What makes metformin unique has been its ability to activate AMPK and to “turn on” youthful controls over cellular functions­—analogous to what happens during calorie restriction.

Benefits Of Enhanced Cellular Energy

Youthful cell metabolism results in glucose and fatty acids being converted to energy instead of stored as body fat. It also enables cells to dispose of accumulated “cellular junk” that contributes to inflammation.

Cancer hates metformin’s uptick in energy efficiency. That’s because in the process of increasing cellular metabolic activity, favorable gene expression changes occur that help destroy malignancies.

Members who have managed to obtain metformin should stay on this drug. For those who are challenged to obtain metformin, or encounter one its side effects such as gastrointestinal upset, there are now plant extracts that produce the same increase in energy efficiency (AMPK activation) as metformin.

You’re going to read about these new plant extracts on the next page of this special winter 2015 edition of Life Extension magazine.

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Dietary anthocyanin-rich bilberry extract ameliorates hyperglycemia and insulin sensitivity via activation of AMP-activated protein kinase in diabetic mice.

Abstract
Blueberries or bilberries contain large amounts of anthocyanins, making them one of the richest sources of dietary anthocyanin. These berries are widely consumed as fresh and dried fruits, jams, or juices. Considerable attention has been focused on the health benefits of bilberry fruits beyond their antioxidant content or their ability to improve vision. In this study, we tested the effect of dietary bilberry extract (BBE) on hyperglycemia and insulin sensitivity in type 2 diabetic mice. We found that dietary BBE ameliorates hyperglycemia and insulin sensitivity via activation of AMP-activated protein kinase (AMPK). Dietary BBE significantly reduced the blood glucose concentration and enhanced insulin sensitivity. AMPK was activated in white adipose tissue (WAT), skeletal muscle, and the liver of diabetic mice fed BBE. This activation was accompanied by upregulation of glucose transporter 4 in WAT and skeletal muscle and suppression of glucose production and lipid content in the liver. At the same time, acetyl-CoA carboxylase was inactivated and PPARalpha, acyl-CoA oxidase, and carnitine palmitoyltransferase-1A were upregulated in the liver. These changes resulted in improved hyperglycemia and insulin sensitivity in type 2 diabetes. These findings provide a biochemical basis for the use of bilberry fruits and have important implications for the prevention and treatment of type 2 diabetes via activation of AMPK.

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Pomegranate vinegar beverage reduces visceral fat accumulation in association with AMPK activation in overweight women: A double-blind, randomized, and placebo-controlled trial

Recent studies on animals have suggested that vinegar consumption may confer an antiobesity effect through the activation of the AMP-activated protein kinase (AMPK) signaling pathway. However, mechanisms of action in humans remain largely unknown. A randomized, double-blind, placebo-controlled trial was performed to examine whether a pomegranate vinegar (PV) beverage alleviates adiposity in overweight subjects, with emphasis on AMPK activation. Seventy-eight overweight women (BMI >-25) were randomly assigned to receive either PV (1.5 g acetic acid and 700 ?g ellagic acid/200 mL/day) or a placebo for 8 weeks. The PV reduced visceral adipose tissue, as measured by computed tomography (P = 0.037), and enhanced AMPK phosphorylation (P = 0.013) compared with the placebo group. The PV tended to suppress downstream gene expression, such as that of sterol regulatory element binding protein-1c and acetyl coenzyme carboxylase, in adipose tissue. Together, these data suggest that PV is an excellent AMPK activator and may exert beneficial effects on adiposity.

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Exercise, which is perhaps the most extreme metabolic stress experienced by normal humans, leads to activation of AMPK in skeletal muscle [21;46;218] and, at least in rodents in intraabdominal adipose tissue, liver [24;141] and probably other organs (J.Cacicedo, M-S. Gauthier, N.Ruderman, unpublished observations). It also has effects on insulin sensitivity [121;156;157] and gene and protein expression in various tissues [67;141;144;206], and in humans it reduces overall morbidity and mortality in an otherwise sedentary population [11]. In contrast, physical inactivity is known to be a powerful risk factor for many diseases and is beginning to be considered as a disease by itself [110]. It can be hypothesized that many of the beneficial effects of exercise and the adverse effects of physical inactivity are related, respectively, to the activation or lack of activation of AMPK. From a biochemical perspective, exercise can be used both as a model to study the mechanisms by which AMPK is activated in skeletal muscle and other tissues and as a tool to unravel its physiological roles in vivo. In this review, we will examine these possibilities, with special emphasis on the apparent ability of exercise to prevent and treat various diseases.

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AMP-activated protein kinase (AMPK) is a key sensor and regulator of glucose, lipid, and energy metabolism throughout the body. Activation of AMPK improves metabolic abnormalities associated with metabolic diseases including obesity and type-2 diabetes. The oriental traditional medicinal herbal plant, Gynostemma pentaphyllum, has shown a wide range of beneficial effects on glucose and lipid metabolism. In this study, we found that G. pentaphyllum contains two novel dammarane-type saponins