Does Metformin Work as a Life-Extension Drug?

Summary

The script explores whether the diabetes drug Metformin has anti-aging properties. Originating from the toxic plant goat's rue, Metformin activates AMPK, potentially reducing blood sugar, cholesterol, and body fat while mitigating fibrosis and slowing cancer progression. Studies suggest Metformin may extend lifespan in C. elegans worms and mice, with observational data indicating a survival advantage in diabetic cancer patients. However, its effectiveness in humans remains a subject of ongoing research.

Takeaways

• 💊 Metformin, a widely prescribed diabetes drug, is being studied for potential anti-aging effects.
• 🌿 The drug originated from the plant goat's rue, which was used in the Middle Ages for treating diabetes symptoms.
• 🔍 Metformin works by activating AMPK, a cellular energy sensor that helps regulate glucose and lipid metabolism.
• 🛡️ AMPK activation by metformin can lead to health benefits beyond blood sugar control, such as reduced cholesterol and body fat.
• 🚫 The original compound from goat's rue, galegine, was too toxic for human use and was modified to create metformin.
• 🏆 Metformin is the most prescribed drug for type 2 diabetes, with over 90 million annual prescriptions in the U.S.
• 🌱 Metformin may also promote the growth of beneficial gut bacteria, adding to its health effects.
• 💉 Observational studies suggest that metformin users have a survival advantage and lower risk of death from cancer.
• 🐛 In C. elegans worms, metformin has been shown to extend lifespan by nearly 40 percent, indicating anti-aging properties.
• 🧬 Metformin's effects on lifespan are still under investigation in mice and humans, with mixed results across different species.
• 👨‍⚕️ Research indicates that diabetics on metformin live longer than those on other diabetes drugs, and even longer than nondiabetics.

Q & A

What is the primary purpose of the drug Metformin?

Metformin is primarily used as a diabetes drug, specifically for managing type 2 diabetes by lowering blood sugar levels.

What historical use of goat's rue is mentioned in the script?

Goat's rue was used as an herbal medicine in the Middle Ages to treat symptoms like thirst and frequent urination, which are now recognized as signs of diabetes.

How does the plant goat's rue produce a compound that could potentially help with diabetes?

Goat's rue produces a mitochondrial poison called galegine. At the right dose, it could impair energy production enough to activate AMPK, which would then reduce the liver's sugar production and lower blood sugar levels.

What was the outcome of the attempt to use galegine in humans?

Galegine proved too toxic for human use and was modified into a milder form, which led to the creation of metformin.

Why is metformin referred to as a 'sugar eater'?

Metformin was sold originally as Glucophage, which means 'sugar eater,' reflecting its role in lowering blood sugar levels.

What are some of the additional health effects of metformin beyond its primary use for diabetes?

Beyond its use in diabetes, metformin also appears to foster the growth of good bacteria in the gut, lower cholesterol and body fat, and reduce the synthesis of excess proteins, which can have health benefits.

How does metformin potentially impact fibrosis?

Metformin, by activating AMPK, can switch the body into energy-conservation mode, reducing the energy budget for superfluous activities like fibrosis, thus potentially slowing down fibrotic processes.

What is the correlation between metformin use and cancer survival rates?

Observational studies involving diabetic cancer patients have shown that those on metformin experienced a significant survival advantage, with a 26 percent decreased risk of dying from cancer.

How does metformin affect lifespan in different species?

In C. elegans worms, metformin can extend lifespan by nearly 40 percent, and it also improves the healthspans and lifespans of mice. However, it failed to extend the lives of rats, possibly due to the high dose used or the specific strain's resistance to calorie restriction.

What are the implications of metformin use in humans in terms of longevity?

Data from metformin trials suggests that diabetics on metformin live significantly longer than those taking different blood sugar-lowering drugs, and even longer than nondiabetics, suggesting a potential pro-longevity effect.

What are the potential downsides of metformin use that might be discussed in further detail?

While the script suggests that metformin has many potential health benefits, it also hints at possible downsides that could be explored in further discussions, such as potential side effects or contraindications.

Outlines

00:00

💊 Metformin: The Anti-Aging Diabetes Drug?

This paragraph delves into the potential anti-aging effects of the diabetes drug Metformin. Originating from the plant goat's rue, which contains the mitochondrial poison galegine, Metformin was developed in the 1950s as a safer alternative. It works by activating AMPK, a cellular energy regulator, which reduces the liver's sugar production and lowers blood sugar levels. Metformin's benefits extend beyond diabetes management, as it also appears to promote good gut bacteria growth and reduce cholesterol and body fat. The activation of AMPK during resource scarcity leads to a conservation of energy and a decrease in fibrosis, which can contribute to various age-related diseases. Metformin has shown to slow cancer progression in observational studies and is currently being tested in over 100 studies against cancer. In animal studies, it has been shown to extend the lifespan of C. elegans worms and improve the healthspan and lifespan of mice, although its effects on rats were less clear. The paragraph concludes with the question of whether Metformin could slow human aging and extend lifespans, hinting at the wealth of data available from metformin trials on humans.

05:01

📊 Metformin's Impact on Longevity and Health

The second paragraph explores the longevity benefits of Metformin for diabetics compared to those taking other blood sugar-lowering drugs. It suggests that Metformin not only manages diabetes effectively but also provides a survival advantage, as evidenced by diabetics on Metformin living longer than those on other medications. The paragraph challenges the assumption that Metformin's benefits are solely due to better diabetes management by comparing the lifespans of diabetics on Metformin to nondiabetics. Remarkably, it is shown that diabetics on Metformin live longer than nondiabetics, suggesting that Metformin may have a lifespan-enhancing effect independent of its diabetes management properties. The paragraph ends by posing the question of whether everyone should be taking Metformin, acknowledging the need to consider potential downsides, which will be discussed in subsequent content.

Keywords

💡Metformin

Metformin is a medication primarily used to treat type 2 diabetes by lowering blood sugar levels. In the video, it is explored for its potential anti-aging effects due to its ability to activate AMPK, an enzyme involved in energy regulation and cellular processes. Metformin's origin is traced back to the herb goat's rue and its active component, galegine, which led to the development of this widely prescribed drug.

💡AMPK

AMPK (AMP-activated protein kinase) is an enzyme that plays a crucial role in cellular energy homeostasis. It is activated when energy levels are low, prompting the body to conserve energy and halt unnecessary processes like new protein and lipid synthesis. The video highlights AMPK's role in mediating metformin's effects, including reducing blood sugar, cholesterol, and body fat, and potentially contributing to longevity and anti-aging.

💡Galegine

Galegine is a toxic compound found in the herb goat's rue, known to impair mitochondrial function. This compound was historically used to treat symptoms of diabetes before being deemed too toxic for human use. The video explains that galegine's mechanism of action inspired the development of metformin, a safer and effective diabetes medication.

💡Life-extension

Life-extension refers to the potential of certain interventions or substances to prolong lifespan. The video discusses the possibility of metformin functioning as a life-extension drug, citing studies on various species, including C. elegans worms and mice, where metformin has shown to extend lifespan by activating AMPK. However, its effectiveness in humans is still under investigation.

💡Calorie restriction mimetic

A calorie restriction mimetic is a compound that simulates the biological effects of calorie restriction without reducing food intake. Metformin is discussed in the video as a calorie restriction mimetic because it activates AMPK, which mimics the body's response to low energy availability, thereby promoting longevity and healthspan benefits similar to those observed with calorie restriction.

💡Fibrosis

Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue, often as a reparative response to injury. The video highlights how metformin's activation of AMPK can reduce fibrotic processes, thereby potentially decreasing the risk of conditions like heart, liver, kidney, and lung fibrosis, which are linked to aging and chronic inflammation.

💡Cancer survival

Cancer survival refers to the likelihood of living for a certain period after a cancer diagnosis. The video mentions that diabetic patients on metformin have shown a significant survival advantage, with a 26 percent decreased risk of dying from cancer. This observation has led to numerous studies investigating metformin's potential as an anti-cancer agent.

💡Healthspan

Healthspan is the period of life during which an individual remains healthy and free from serious disease. The video suggests that metformin not only extends lifespan but also improves healthspan by reducing age-related susceptibilities such as fractures, infections, glaucoma, and cognitive impairment, thus enhancing overall quality of life in diabetic patients.

💡Observational studies

Observational studies are research methods that involve observing and analyzing outcomes without manipulating variables. The video references dozens of observational studies involving tens of thousands of diabetic cancer patients to support the claim that metformin users experience better survival rates, providing a basis for further research into its potential anti-aging and anti-cancer benefits.

💡Longevity

Longevity refers to a long duration of life. The video explores the concept of longevity in the context of metformin, discussing how this diabetes drug might extend life expectancy by activating AMPK, thereby mimicking the effects of calorie restriction and promoting a shift from growth to preservation processes in the body.

Highlights

Metformin, a diabetes drug, is being studied for its potential anti-aging effects.

Goat's rue, an ancient herbal medicine, contains galegine, a compound that led to the development of metformin.

Galegine impairs energy production, activating AMPK, which reduces liver sugar production and lowers blood sugar levels.

Metformin, derived from galegine, is now the world's most widely prescribed diabetes drug.

Metformin, originally sold as Glucophage, is prescribed more than 90 million times annually in the U.S.

Metformin not only ramps up AMPK but also promotes the growth of beneficial gut bacteria.

AMPK activation by metformin leads to energy conservation and a reduction in the synthesis of excess proteins, cholesterol, and body fat.

Metformin's suppression of fibrosis may contribute to its health benefits, as fibrosis is linked to 45% of deaths in the U.S.

Observational studies show metformin users have a 26% decreased risk of dying from cancer.

Metformin has been shown to extend the lifespan of C. elegans worms by nearly 40%.

Metformin's effects on lifespan extension in mice support its potential as a longevity drug.

In rats, metformin did not extend lifespan, possibly due to a high dose and the specific rat strain used.

Data from over a million metformin trial subjects suggests potential anti-aging benefits in humans.

Diabetics on metformin live significantly longer than those on other blood sugar-lowering drugs.

Contrary to expectations, diabetics on metformin have been shown to live longer than nondiabetics.

The potential of metformin as a pro-longevity drug raises questions about its widespread use and safety.

Transcripts

Might the diabetes drug Metformin have an anti-aging effect?

Check out this 3-video series to see what the science says.

"Does Metformin Work as a Life-Extension Drug?"

The noxious weed goat's rue

was widely used as an herbal medicine

back in the Middle Ages for thirst and frequent urination,

what we now know of as a cardinal symptom

and sign of diabetes.

The plant produces a mitochondrial poison

known as galegine.

One can imagine how this could help discourage

grazing herbivores,

but why would crippling mitochondrial function

help with diabetes?

Well, if you got the dose just right,

you could impair energy production just enough

to spring AMPK into action.

AMPK would then dial down

the liver's energy-intensive process

of sugar production, and blood sugars would fall.

Galegine proved too toxic for use in humans

(and presumably goats)

but was tweaked into a milder form in the 1950s.

That's the origin story of metformin,

now, even 60+ years later

the most widely prescribed diabetes drug in the world.

Sold originally as Glucophage (meaning "sugar eater"),

metformin is now prescribed annually

more than 90 million times in the U.S. alone.

Despite all the strides in biotechnology,

Big Pharma has yet to come up with a safer,

more effective first-line treatment

for type 2 diabetes than a drug

that retails at pennies per pill.

Ramping up AMPK isn't all that metformin does

(for example, it also appears to foster the growth

of good bacteria in the gut).

But the AMPK boost alone would be expected

to have wide-ranging health effects.

Remember, AMPK is activated when resources are scarce;

so, it causes the body to hunker down

into energy-conservation mode

and put the brakes on new construction projects.

So, no more making excess blood sugar or cholesterol.

Time to start tapping into the larder.

And, indeed, metformin doesn't just lower sugars in the blood

but cholesterol and body fat.

And shutting down the excess synthesis of proteins

can also have health benefits.

Fibrosis is the accumulation of scar tissue

in response to an inflammatory insult.

As a transient, localized phenomenon,

fibrosis helps heal wounds and repair damaged tissue,

but in response to the systemic inflammation of aging,

surplus scar tissue can build up in our heart,

liver, kidneys, and lungs.

Excess fibrosis is estimated to contribute to 45 percent

of all death in the United States.

But AMPK switches the body into miser mode,

shrinking the energy budget

for such superfluous activities

and ratchets down fibrotic processes.

The AMPK priorities shift from growth to preservation

might also be expected to slow cancer progression.

Based on dozens of observational studies

involving tens of thousands of diabetic cancer patients,

those on metformin did indeed experience

a significant survival advantage,

correlating with a 26 percent decreased risk

of dying from cancer.

No wonder there are more than 100 ongoing studies

to put metformin to the test against cancer.

As the director of Harvard's Cancer Center put it,

"Metformin may have already saved more people

from cancer deaths than any drug in history."

If AMPK plays such a key role

in the aging process,

and metformin boosts AMPK,

can metformin slow aging

and lengthen lifespans?

It certainly can in some species.

C. elegans worms fed metformin

maintained a youthful state

and can exhibit a nearly 40 percent increase

in average survival.

Interfere with the AMPK pathway, though,

and this lifespan extension disappears,

confirming the role of AMPK

in metformin's anti-aging effects.

Metformin also improves

the healthspans and lifespans of mice,

but failed to extend the lives of rats,

calling the pro-longevity effects of metformin

into question.

The dose they used

(15 times that used in humans)

may have been too high, however,

and the F344 rats they used

are an inbred strain

(named after the 344th brother sister mating)

that are resistant to the health benefits

of calorie restriction.

Since metformin acts through AMPK

as a calorie restriction mimetic,

it stands to reason that these animals

may be less prone to metformin's effects.

What about humans?

Unlike other potential

anti-aging drugs in the pipeline,

we have the benefit of data

on more than a million study subjects

who have been tracked in metformin trials.

And, indeed,

compared to diabetics

who take drugs other than metformin,

those on metformin appear protected

from age-related susceptibilities,

like fractures,

or serious infections,

glaucoma,

and cognitive impairment.

Most importantly,

diabetics who take metformin

live significantly longer

than those taking different blood sugar-lowering drugs.

Doesn't that prove metformin

is a pro-longevity drug?

No.

For example, maybe metformin

just controlled their diabetes better.

Researchers still found a survival benefit

for diabetics on metformin

compared to those as well managed on other drugs,

but maybe the other drugs

were shortening lifespans,

and so, metformin just looked good in comparison.

How could you try to tease out the effects?

What if you compared the lifespans

of diabetics on metformin

to nondiabetics?

Now, that's not really a fair comparison.

Any benefits metformin has

could easily be outweighed and masked

by the life-limiting nature of diabetes--

unless, that is,

the diabetics on metformin

actually lived longer.

Longer than nondiabetics.

And,

are you sitting down?

That's exactly what the research shows.

Diabetics placed on metformin

went on to live longer lives

than those who never got diabetes in the first place.

From a longevity standpoint,

it's as if they got lucky

to be diagnosed with diabetes,

because then, they had access to this lifespan-enhancing drug.

So, wait.

If metformin is so powerful

as to more than offset such a dreaded diagnosis,

should everyone be taking metformin?

What are the downsides?

That's exactly what I'm gonna be covering next.