Episode 4: NMN, NR, Resveratrol, Metformin & Other Longevity Molecules

Longevity Molecules

• mTOR, AMPK, Sirtuins -

  • They talk to each other, and some supplements work on multiple pathways.

  • These are the “survival pathways”.

NAD Boosters

• Our cells use NAD to transfer hydrogen atoms between proteins and even DNA.

  • Needed to be alive.

• NAD is very abundant

• NAD helps us make energy.

• NAD’s activates the sirtuins (defensive enzymes)

• As we get older, we create less NAD.

• Fasting and exercise increase NAD levels. But as you age, you will create less NDA.

Nicotinamide Riboside (NR)

• Vitamin b3 + Sugar

• NR is OTC since 2014.

• Many human studies show little to no side effects.

• 250 mg - 1g

• Yeast with NR lived 30% longer.

• NR → Gut → Blood Stream → Taken into muscles, cells, tissues via ENTs → Converted into NMN by NRKs → Add phosphate → 2 NMN put together create NAD.

• NR given to old mice extends lifespan by 9%.

  • More mitochondria

  • More athleticism, less inflammation.

• It needs phosphate for NR to turn into NAD.

• Studies show that it increases NAD levels after 9-10 days

  • Lower blood sugar, less inflammation.

  • Not many long-term effects have been studied.

Nicotinamide Mononucleotide (NMN)

• The closer you get to NAD, the easier it will be to create NAD.

• Many labs show NMN works better at the same dose (unsure why).

• Specific transporter (SLC12aa) might explain how NMN gets into cells.

• Not sure why NMN works, but it’s clear that it does work.

• Mice live longer by 10-15% with NMN.

  • Works better in female mice.

  • Preliminary study

  • Hard to see a full lifespan study cause mice live 2-3 years.

• NR and NMN have similar effects, but NMN is more effective.

• NMN has not shown any negative side effects.

• Not many human studies on NMN.

• 250mg - 1g dosage.

NAD Directly?

• NAD Drips

  • People in Florida have been doing drips under medical supervision.

  • No actual studies don’t on NAD drips.

  • It has been used to treat addiction, hangovers, and depression.

• Giving yeast NAD directly didn’t work; it’s too big.

  • The smaller the molecule, the easier it is for the cell to pick it up.

Best Way to Consume

• The best way to take it is to ingest it (pills or powder).

  • No research shows that one is better than the other.

NAD Booster and Cancer

• Studies show that lower NAD in cancer patients shows a slowing of the tumor (in mice).

• NAD boosters can increase cancerous growth for mice that already have cancers, or so it seems.

• Not a lot of strong data around this; consult your physician.

Resveratrol

• Cert 1 (1/7 sirtuins) is increased by 13x by resveratrol.

• Resveratrol is found in red wine.

  • You would need to drink an absurd amount of red wine to get the necessary amounts of resveratrol.

• You can get resveratrol from plants.

• 250 mg - 2000mg a day.

• You can’t simply swallow it with water.

• It needs to be mixed with food, yogurt, or olive oil.

  • Resveratrol is hydrophobic.

• Resveratrol given to rodents shows:

  • Protected against western diet.

  • Fat mice on resveratrol lived as healthy and long as lean animals.

  • It shows similarity in humans.

• Resveratrol has been shown in humans to:

  • Reduce fasting glucose

  • Increase insulin sensitivity

  • People with 30 BMI were able to lower LDL, urea levels and increase HDL.

• Known as an agent to prevent cancer.

• French Paradox

  • Drinking red wine over 30 years can have an accumulative effect.

Fisetin and Quercetin

• Sirtuin activators

• Cenalytic - Kill senescent cells (zombie cells that have bad epigenome)

• Fisetin has been shown to increase lifespan in mice by up to 30%

  • By removing senescent cells and activating cert-1 defenses.

• Quercetin

  • Show remarkable results for longevity.

  • Reduces inflammation and liver fat.

• Requires more human studies.

Rapamycin and Rapalogs

• Inhibit mTOR (mimics fasting).

• They are used for immune suppression.

• Not many studies on humans.

• It has been seen to be effective on non-human organisms.

• Rapamycin mimics adversity.

Spermidine

• Crystals in sperm are spermidine.

• Extends lifespan in mice and other organisms.

  • Live longer and have other youthful capacities.

• Stimulates autophagy in the mTOR pathway.

• Stabilizes changes in the epigenome (x-differentiation).

• Cognition is improved in older Americans.

• Now it is gotten from wheat germs.

Metformin

• AMPK activator

• Used in type 2 diabetics.

• OTC in most parts of the world.

• Many theories of how AMPK is activated.

• Perceived adversity impacts a few pathways.

  • Lower energy, activating AMPK

  • Increases NAD levels, activating the sirtuins.

• Mice on metformin were healthier and longer-lived.

• Muscle switching is improved in humans who take metformin.

• Metformin reduces the likelihood in chances of getting other diseases.

• Study to show that aging can be slowed down by metformin.

• People are now taking metformin with the approval of their physicians.

• Metformin has downsized

  • Can cause lactic acisidocis.

  • Lack of hunger, upset stomach.

  • Doesn’t make a big difference in muscle size, (5%). Can lower muscle size, but also decreased inflammation.

Berberine

• Take it with olive oil or yogurt.

• It works very similarly to metformin.

• Higher doses, 1-2g

• Shown substantial increases of lifespan in mice and fruit flies.

Dr. Sinclair’s Protocol for Longevity Molecules

• Morning

  • 1 Gram of resveratrol each morning.

    • Yogurt or olive oil.

    • Taken in the morning, you can take it with a fast, just not too much food.

  • 1 Gram of NMN each morning.

    • Based on human studies.

  • .5 a gram of Fisetin and Quercetin in yogurt.

  • 1 Gram Spemidity

    • Recently adopted

  • It is good to take in the morning as it correlates with our circadian rhythm and natural secretion of NAD by the body.

• Night

  • 800 milligram of metformin at night.

    • After dinner.

    • Skips them on the night before an exercise.