Longevity Supplements - What Works & What Doesn't? | Dr. Richard Miller, Interventions Testing Program

Live Longer World Podcast #18

“We’re just about to submit a paper where we’ve tested two drugs - Rapamycin + Acarbose - and that gives us the best % increase in males (mice) we’ve ever seen - we’re getting about a 29% (lifespan) increase in males. Acarbose did not improve upon just Rapamycin in females.”

Live Longer World Podcast Episode #18 has been released!

Dr. Richard Miller runs one of the labs for the Interventions Testing Program or the ITP, which is largely considered the gold standard for testing longevity drugs.

This was one of the best conversations I’ve had on longevity supplements that affect lifespan and those that might me subject to mere hype. Dr. Miller is rigorous in his approach and states the data clearly. He also has opinions on lifespan vs. healthspan that are unique from those of most others and worth paying attention to.

I genuinely walked away having learned so much from this conversation and feeling more awakened, and I hope it is useful to you too in parsing the data out there on longevity supplements. Best, Aastha.

In today’s episode, you will learn:

• The 4 winning drugs that increase lifespan in mice as tested by the ITP:

  • Rapamycin

  • Acarbose

  • 17-alpha estradiol

  • Canagliflozin

• 3 other drugs that produce small lifespan benefits: NDGA, Glycine, Captopril

• Drug combinations:

  • Rapamycin + Acarbose

  • Rapamycin + Metformin

• Drugs that show no lifespan increase in mice in the ITP:

  • Resveratrol

  • Nicotinamide-Riboside (NR)

  • Fisetin

  • Curcumin, MCT Oil, Green tea extract, Fish Oil

• Richard’s thoughts on lifespan vs. healthspan

If you are a premium subscriber, you can also read the summarized notes of these learnings below.

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Time Stamps:

0:55 Richard Miller Intro

1:51 Richard Miller Wildlife photography

3:30 ITP - the gold standard for testing longevity drugs & winning drugs

10:51 Rapamycin, Rapamycin + Acarbose

18:48 Rapamycin + Acarbose Dosing Schedule

20:15 Combination of drugs, Rapamycin + Metformin

21:56 17-Alpha Estradiol

25:45 Canagaflozin

31:34 Does Richard take the 4 winning drugs?

32:46 3 Drugs that have small lifespan effects & promising

36:30 GPLD-1 & shared mechanisms in longevity drugs

44:04 Resveratrol in ITP

46:27 NR, NMN

52:34 Curcumin, Green Tea Extract, MCT Oil

54:54 Fisetin & Senolytics

56:12 Why most published research findings are false

1:00:03 Healthspan biomarkers at the ITP

1:02:38 Can you have healthspan without lifespan?

1:07:37 Fish Oil, Spermidine, Sulforaphane

1:12:13 Unpublished data Richard is excited about

1:17:47 Flying Pigs & Aubrey De Grey

1:20:00 Exponential rise in aging research

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Podcasts Referenced / Related Content:

1. Aging Interventions - Rapamycin, NAD+ & Dog Aging Project | Matt Kaeberlein

2. Aging Networks & Biomarkers, Alpha-Ketoglutarate & Longevity of Bats | Dr. Brian Kennedy

3. Centenarian Longevity & Metformin | Dr. Nir Barzilai

4. Aging: What is it & How to Slow, Reverse and Measure it

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Premium Subscriber Show Notes:

There is so much hype on longevity supplements and I think you’re one of the best people to talk to to tell us what the data actually says. You run the Interventions Testing Program or the ITP which is largely considered the gold standard for testing longevity drugs. Before we dive into discussing some of the supplements tested by the ITP, can you explain - what is the ITP and how does it work?

• About 20 years ago, we decided to have an organized multi-institution program to see if it might be time if adding drugs to mice would slow a wide-range of age-associated diseases. So the initial grants were made to 3 institutions

• Drugs are suggested by anyone, including people listening to this, who can suggest which drug should be tested and why

• We test drugs at 3 different locations to see if the results are actually reproducible

• We screen 5-7 new drugs a year and most of them don’t work! At this stage, we’ve had 4 published drugs and 2 unpublished ones that give strong benefits, which in this case is 10% or more

• 20 years ago, people were sure we couldn’t control aging, but we have shown that’s not true. Aging is complicated but there are pathways in mammals that you can mess with and will postpone a wide-range of diseases

• Further, each drug that works, gives scientists more information on what pathways are being affected and which ones to study

WINNING DRUGS IN THE ITP:

Rapamycin - what do ITP results say:

• Originally tested rapamycin at 14mg for every 1kg of food and led to 20% lifespan in females and 15% lifespan increase in males

  • This might suggest that rapamcyin works preferentially better for females than males, but it’s not necessarily the case

  • At any given dose of rapamycin given in food, the blood concentration is higher in females than in males

• When you give rapamycin by itself at higher doses, it gives 26% lifespan increase in females and 23% in males

• Why are there sex-specific differences? Not sure yet, but the most plausible explanation is how the drugs work in different tissues in both sexes or the speed with which they are conjugated and secreted. Any of these steps could be different in females vs males which affects the blood concentration levels

• We tested rapamycin at 2 different ages:

  • First group: Mice at 9 months of age (for humans that’s 30-35 years)

  • Second group: Mice at 20 months of age (for humans that’s 60-65 years)

• We thought that we would get more lifespan increase for the 1st group but that was not the case! We saw the same lifespan increase for both groups. This suggests that are rapamycin sensitive events happening even at later ages and could be used to postpone diseases much later

• Also tested rapamycin at different dosing schedules:

  • Group A: Started rapamycin at 20 months of age for the rest of their lives. Got all the lifespan benefits

  • Group B: Started rapamycin at 20 months of age and cycled every month (1 month on, 1 month off).

    • For males, the cycling worked just as great as having it everyday

    • For females, the results were only half as good as taking rapamycin everyday

  • Group C: Started rapamycin at 20 months of age everyday for 2 months and then stopped