Billions of dollars are spent every year with one goal in mind — to maintain youth. Creams are applied, surgeries undergone, and extreme exercise or calorie restriction executed to maintain a youthful glow and youthful function. Knowing this, scientists have performed thousands of hours of research in search of the next miracle drug, molecule, or supplement to extend healthy human lifespan. Recent discoveries of cellular pathways — AMPK and mTOR — make this dream more of a reality.
What is AMPK?
Adenosine monophosphate-activated protein kinase (AMPK) is an important enzyme found inside every cell in the body. It serves as a master regulator of energy metabolism. AMPK detects energy levels (the number of ATP molecules) inside cells and controls responses when ATP levels are too high or too low. When activated, AMPK speeds metabolism, accelerates fat burning, and even influences how long you live.
Its activity level also closely regulates aging. The enzyme is most active in days of youth but its activity gradually decreases with each passing year. (1) This decreased activity is partially responsible for the buildup of visceral (belly) fat and muscle loss that occurs during the aging process. Excess weight, and the accumulation of fat around the waistline, accelerates aging. (2) Abdominal fat also generates an abundance of inflammatory chemicals. Indeed, deep abdominal fat transforms into an inflammation-promoting factory, leading to metabolic diseases. (3)
What happens when AMPK activity decreases?
Given that AMPK is the master cellular regulator of metabolism, it’s not surprising that a whole host of adverse effects can occur when its activity slows down.
- Chronic inflammation
- Increased visceral fat
- Accelerated aging
- Dyslipidemia (high LDL cholesterol and triglycerides; low HDL)
- Mitochondrial dysfunction
- Poor blood glucose control
AMPK promotes cellular renewal and clean-up
Your cells continuously generate energy to remain viable. The process of energy creation produces toxic debris and metabolic waste that must be carefully managed by your body. Autophagy is the primary process cells use to clear damaged proteins and mitochondria, and other metabolic waste products. It is your cell’s internal housekeeping process.
The easiest way to think about this process is to consider fireplaces and a chimney sweep. Fireplaces are your cells. Inside these fireplaces, a series of oxidation reactions occur to convert food molecules into energy. As a result, the inside of the cell accumulates debris (like soot). The chimney sweep is autophagy, which cleans out the debris so the cell can operate more efficiently. Maintaining optimal autophagy is critical to cellular health and function.
Emerging scientific research suggests that autophagy is involved in virtually every intervention proven to extend healthy lifespan. (4) This discovery is a major advance in the quest to slow and reverse the aging process.
mTOR: AMPK’s partner in longevity
AMPK regulates autophagy and fat-removal partly by modulating a protein, and its partner in crime, called mTOR. mTOR stands for mechanistic target of rapamycin (an immunosuppressive drug that targets mTOR activity), and when properly balanced, triggers the breakdown of fat stores to produce cellular energy. (5) Indeed, scientists have discovered that mTOR functions as a central coordinator of metabolism and cellular growth in response to environmental and hormonal signals.
In essence, mTOR is the master conductor of your cellular symphony of processes. mTOR responds to stimuli such as amino acid levels, cellular energy status, oxygen level, and insulin growth factors. Its two complexes (mTORC1 and mTORC2) serve as a communication hub that integrates cellular nutrient and stress statuses and then formulates an appropriate response.
Like AMPK, mTOR activity is directly associated with the aging process. Animal research demonstrates that decreasing mTOR activity extends lifespan. (5) Conversely, mTORC1 signaling activity is increased in a number of diseases, including cancer. (5) The discovery of mTOR’s involvement in aging and age-related diseases creates an exciting prospect to not only delay aging, but reduce the risk of age-related diseases like cancer and Alzheimer’s disease.
The role of exercise and eating in AMPK activation and mTOR regulation
Before we explore proven natural solutions to slow aging at the cellular level, it is important to emphasize the importance of regular exercise and eating better. It’s no revelation to those who live a healthy lifestyle that vigorous activity and reducing caloric intake are two well-established strategies to active AMPK activity and regulate mTOR. (6)(7) Calorie restriction triggers mechanisms that improve metabolism efficiency and protect against cellular damage. Many of the health benefits of exercise are linked to mTOR activity in muscle, brain, fat, and liver tissue. (8) Achieving optimal AMPK and mTOR activation is therefore critical for overall health and healthy lifespan.
Health really is a product of what you eat, how you move, environmental factors, and your thoughts and emotions. You simply can’t outpace the effects of poor eating, inactivity, or chronic stress. Nutrition and regular activity are foundational and the longevity results achieved with other natural measures will be amplified when they are properly established.
Natural methods to increase autophagy and AMPK activation and regulate mTOR
- Gynostemma pentaphyllum (Jiaogulan). Dubbed the immortality herb for good reason, jiaogulan is prized for its ability to promote youthfulness and longevity. Its health benefits are often attributed to its effects on AMPK activity. Laboratory research demonstrates that GP potently increases AMPK activation almost seven-fold (660%). (9A)(9B)(9C) Remarkably, that is far greater than increases achieved with the diabetes drug metformin (1.3–1.6-fold increase) — metformin’s best-studied mechanism of action is through AMPK activation. (10) A randomized clinical study showed GP busts abdominal fat. Scientists observed an 11% reduction in visceral fat when individuals took 450 mg daily. (11)
- Hesperidin. The citrus bioflavonoid hesperidin also significantly increases AMPK. Clinical research suggests that hesperidin benefits people with metabolic syndrome (high blood sugar, high blood pressure, dyslipidemia, systemic inflammation, and excess abdominal fat). What scientists found was that hesperidin (400 mg to 500 mg daily) reduces systemic inflammation and abdominal fat. (12)(13)
- Nicotinamide riboside. Preliminary research suggests that the NAD precursor nicotinamide riboside potently triggers autophagy, and improves mitochondrial function to extend lifespan. (14)(15) Typical doses are 100 mg daily.
- Citrus bergamia (Bergamot) essential oil. Both bergamot essential oil and one of its primary constituents (limonene) stimulate autophagy according to laboratory research. (16)
- Boswellia species (Frankincense), Pinus densiflora (Pine), and Pelargonium graveolens (Geranium) essential oil. Researchers discovered that three essential oils modulate the activity of the AMPK/mTOR signaling pathway. (17) Regulation of the AMPK/mTOR pathway is likely best achieved through ingestion of the essential oils. Perhaps as few as 1-3 drops daily may be effective. This will need to be determined by clinical research.
Turning down mTOR and activating AMPK (and therefore autophagy) is not for everyone. Those with sarcopenia (degenerative loss of muscle tissue) or other frailty-associated conditions could experience aggravation of symptoms through chronically decreased mTOR and elevated autophagy. (18)
Emerging evidence surrounding the AMPK/mTOR signaling pathway is an exciting cellular pathway to slow down the aging process and reduce age-related disease burden. Even more exciting is the possibility of influencing aging and age-related diseases with natural products. Don’t take your chances with expensive and risky surgeries to look and feel younger. Mother Nature prepared multiple solutions that you can give a try instead.