Jennie Ann Freiman M.D.
May 15, 2017
The search for eternal life isn’t new, but how far we’ve come from the Holy Grail, the Fountain of Youth and the hidden valley of Shangri-La, is truly a sign of the times. Today, the crossroads meet between the natural tendency to find an easy way out, and the seductive promise of profits. The quest is on for how to put longevity in a pill.
Classifying age as a disease means insurance companies will cover treatment. The FDA just paved the way.
Two years ago, investigators convinced the FDA to green-light a human lifespan study of Metformin, a drug currently used as first-line treatment for blood sugar control in type 2 diabetes, and off-label for polycystic ovary syndrome, weight control, and cancer prevention. If successful, Metformin will be the first drug to be FDA-approved for the indication of aging, but it won’t be the last. With a potential audience of 7½ billion people worldwide, pharmaceutical companies will race to fund clinical trials for the discovery of new, more expensive drugs.
High levels of blood sugar and insulin are important factors in degenerative disorders, cardiovascular disease, cancer, and aging. Metformin lowers blood sugar in two ways, by using it efficiently and preventing its production in the liver. This, in turn, lowers insulin levels and insulin resistance. The drug intrigues researchers because its protective effect on aging goes beyond the power to control sugar and insulin.
Everything Metformin can and might do for healthy aging can be achieved with lifestyle choices.
The TAME Study (Targeting Aging With Metformin) began in 2016, aiming to enroll 3,000 seniors, ages 70 – 80, and study them for 5 – 7 years at 15 centers across the U.S. Study subjects can have or be at risk for any or all of 3 common aging conditions: cancer, heart disease, and dementia. The study excludes type 2 diabetics because the effect of Metformin has already been shown in that group. The question is whether Metformin can delay or prevent cancer, heart disease, cognitive impairment, diabetes and death in non-diabetics. If it does, the obvious next step is to test it for use in much younger people.
Clues about Metformin’s role in anti-aging come from studies of fruit flies, roundworms, and mice. Most of the credit goes to an enzyme few people have heard of, AMPK (adenosine monophosphate-activated protein kinase). AMPK regulates how cells process energy, which, when working well, helps prevent all of the chronic diseases associated with aging, and aging itself. The goal is to activate AMPK to gain its benefits and live a healthier, longer life.
AMPK Benefits For Healthspan And Lifespan:
- Increases metabolism
- Burns fat and sugar / Weight loss
- Improves body composition
- Increases blood flow
- Cell detoxification and renewal
Is Metformin the anti-aging miracle drug researchers hope for, or will it go the way of some other FDA “miracles” before it? Fen-Phen Vioxx, Meridia, Baycol, and DES, are just a few that come to mind.
There is good reason for skepticism:
- Aging is a chronic, inflammatory process that leads to a loss of structure and function, impairing both healthspan and lifespan. Aging is best addressed with health and longevity promoting strategies, not disease prevention.
- Aging is multifactorial. Elements that benefit or harm longevity work together in synergy. The magic bullet approach, focusing on one aspect of disease, works for simple problems like treating a strep throat with penicillin, but disappoints for complex chronic disorders and aging. It has failed over and over, but investigators refuse to let it go.
- Every drug has side effects and risks that must be weighed against its benefits. Metformin carries a black box warning for the rare, but real, risk of developing lactic acidosis, a potentially fatal build-up of lactate in the blood, especially for anyone with reduced kidney function. More common side effects are nausea, vomiting, diarrhea, headache and drowsiness. Let’s don’t forget the “inactive ingredients” that act as toxic counterweights to any drug benefits:
FORTAMET® Extended-Release Tablets. In addition to the active ingredient metformin hydrochloride, each tablet contains the following inactive ingredients: candelilla wax, cellulose acetate, hypromellose, magnesium stearate, polyethylene glycols (PEG 400, PEG 8000), polysorbate 80, povidone, sodium lauryl sulfate, synthetic black iron oxides, titanium dioxide, and triacetin.
- Metformin may promote Alzheimer’s Disease. Type 2 diabetes is a risk factor for Alzheimer’s, so researchers assume drugs that treat diabetes will prevent dementia. Unfortunately, studies link long-term Metformin use to a greater risk of developing AD and worsening its progression. One study proposed this occurs because the drug increases production of beta-amyloid, a protein universally recognized as a hallmark of Alzheimer’s.
- Studies suggest Metformin may accelerate existing cancer and cancer-related mortality by promoting AMPK-induced cellular uptake of glucose, which effectively feeds the tumors cells.
- Aspirin, a more widely used drug than Metformin, also activates AMPK and may be a safer choice if going the drug route. Metformin is pro-inflammatory.
Generally, when something sounds too good to be true, it is. Activating AMPK promotes longevity, but isolating one strategy from the context in which it normally occurs, is like a game of Jenga: disrupt the delicate balance and the whole thing falls apart.
There is a better way.
Natural anti-aging approaches exist and have been scientifically validated. They take commitment and they’re not easy but they avoid the inevitable downside of chronic drug use. They activate AMPK and all of its interrelated systems.
- Calorie restriction is the most successful method of slowing and reversing markers of aging. The idea is to lower calorie intake a moderate amount to induce a healthy level of stress that strengthens cells and organ, but not so much as to cause malnutrition. The ongoing CALERIE study is monitoring healthy individuals committed to a 25% reduction in caloric intake. So far, results are promising.
- Intermittent fasting (also known as “time-restricted feeding”) is an alternative to calorie restriction. Confining eating to an 8 to 12-hour daily window reduces inflammation and free radical damage, and has been shown to fight dementia, cancer and promote longevity.
- Exercise uses up energy, which activates AMPK. High intensity, short interval exertion is especially effective. Muscle contraction during both aerobics and weight training stimulates AMPK and increases insulin sensitivity.
- Cold water immersion after exercise enhances AMPK and cellular renewal. Going from the sauna into the plunge pool, or taking an ice cold shower after a workout are easy ways to practice cold shock. It’s great training for the annual Polar Bear Challenge.
- Healthy eating habits activate AMPK. Go for a well-rounded diet of unprocessed, highly colorful foods including:
- Get good sleep. Impaired quality and/or quantity of sleep is incompatible with long-term health. For example, obstructive sleep apnea is related to a 20% reduction in life expectancy, weight gain, heart disease, diabetes, earlier than average age of onset of memory disorders and cognitive impairment. Melatonin, the sleep hormone, activates AMPK and cellular rejuvenation, protecting against cardiovascular and other sleep deprivation related disorders.
- Acupuncture is effective in treating obesity and improving cognitive function. It upregulates AMPK in the hippocampus, the brain center for short term memory and ground zero for the development of Alzheimer’s Disease.
These and other natural anti-aging strategies are consistently practiced in Blue Zones, unrelated regions around the globe where the most long-lived people are found. Drugs and “longevity genes” are not the reason this Guinness World Record-worthy group boasts a large number of centenarians. Their way of life is the secret sauce for extending healthspan and lifespan.
Whatever your age, it’s never too late for a healthy system reboot. Start now, by adopting a lifestyle game plan that promotes healthy longevity.
Next stop, Methuselah.
black box warning:
Healthy eating habits:
Melatonin, the sleep hormone:
other natural anti-aging strategies: