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Do Longevity Drugs Exist Now? (Yep)

Longevity drugs do exist, as proven by the National Institute of Aging’s Interventions Testing Program. I’ll show you which ones extend lifespan in mice. That has value, because some drugs that benefit mice do find their way to us, so it’s wise to keep up with those critters and the scientists that make them live longer.

Do longevity drugs exist?

I mean, despite all the assertions made by some supplement companies, scientists and biohackers — are there really any longevity drugs that have been proven to extend lifespan in double blind, placebo experiments that have been replicated in various labs?

The fast answer is both “yes” and “no”: Yes in mouse experiments; no in human trials that can stand up to scrutiny.

In this post, I will reveal which drugs have extended the lifespan of mice; drugs that are regularly used by humans, but typically not for life extension, at least not with the approval of the medical establishment.

Why should you care, given that you’re — and I’m guessing here — not a mouse?

You should care because there’s a lot we have in common with mice, genetically and biologically speaking, and sometimes a drug that improves the life of mice, improves ours as well. I encourage you to follow the lifespan studies in mice — some will pave the road for us too.

This post will get you started.

Let’s dig in.

 

Of Mice and [Wo]Men

Let’s begin with the obvious — it’s problematic to study aging in humans. So, scientists need to study other creatures that pretty much age the same way. Mice fit the bill.

That some longevity drugs have actually increased the lifespan of mice is remarkable, and good news for us, because it may portend what could happen in humans as well. But, unlike with mice, it’s exceedingly difficult to test any intervention on a long-lived species like humans for various reasons, two of which are obvious:

1. Humans will not agree to have their lives controlled for several decades by a cabal of scientists; and
2. Even if they did, such experiments would be prohibitively expensive.

Rhesus monkeys are much more human-like than mice, and they were the cohort used in two famous experiments that, like many before and after using various other animal cohorts, showed that caloric restriction can increase lifespan in all animals tested. Even so, with a lifespan of about 40 years, Rhesus monkeys are also typically out of bounds to test longevity drugs.

So, long-lived animals are out of bounds. The animals that scientists do want to use to study potential longevity drugs are animals that:

• Have a naturally short lifespan
• Are easy to genetically manipulate, if needed
• Are cheap to buy and maintain
• Reproduce quickly
• Have similar genetic and biological traits to humans
• Don’t have lawyers

Murines fit the bill (mice and rats).

Almost all of the genes in mice share functions with the genes in humans. That means we develop in the same way from egg and sperm, and have the same kinds of organs (heart, brain, lungs, kidneys, etc.), as well as similar circulatory, reproductive, digestive, hormonal and nervous systems. Likewise, mice and humans — as well as many animals — tend to age similarly.

Dr. Richard Miller, who I’ll tell you about in a minute, put it this way in an interview with journalist Arkadi Mazin:

In terms of aging, if I tell you that I have an individual right here in front of me, in my office, that has cataracts, bad hearing, weakened bones, a poor immune system, and a relatively low cardiovascular system, you would immediately recognize that individual as old, be it a mouse, a dog, a horse, or a person. But you wouldn’t know if that’s a seventy-year-old human, or a 25-year-old horse, or a three-year-old mouse.

So, the effects that aging has on mice and on humans are – not in every case, of course, but in most cases – recognizably quite similar. And that’s true for cells that divide, for cells that don’t divide, for structures like the bones and the tendons that are mostly extracellular material. It’s true for complicated circuits, like neuroendocrine feedback circuits, it’s true for cognition.

There are just so many aspects – not all, but so many aspects of aging in humans, mice, dogs, chimps, et cetera that are the same. So, it’s very reasonable to expect that the drug that could block aging effects in all of those tissues in mice might also do very similar things in people.

That Richard Miller knows what he’s talking about is pretty much indisputable.

 

Of Mice and ITP

In 2002, the National Institute of Aging in the United States began funding the Interventions Testing Program (ITP), a peer-reviewed program designed to identify agents (compounds, molecules and the like) that extend lifespan and healthspan in mice.

Just about any serious person with a good argument for testing some potential longevity drug can petition the ITP to study it. Testing is carried out in the same type of mice at three sites — the Jackson Laboratory, the University of Michigan, and the University of Texas Health Science Center at San Antonio.

To have three different sites is purposeful. The aim is to test if all three sites with different labs and scientists can come up with the same results. If they do, then there’s a higher degree of confidence that the test outcomes are correct.

Testing in the ITP is carried out in two stages:

• Stage I tests a single dose of an agent to determine its effect on lifespan.
• Stage II tests additional doses or alters treatment start times to determine the effects of the agent on lifespan, age-sensitive health measures, and pathology.

Proposed interventions can be pharmaceuticals, nutraceuticals, dietary supplements, plant extracts, hormones, peptides, amino acids, chelators, redox agents, or other agents, or mixtures of compounds. Priority consideration will be given to interventions that are easily obtainable, reasonably priced, and can be delivered in the diet.

Richard Miller, MD, PhD, mentioned above, heads the ITP. Dr. Miller is highly credentialed: In addition to

his leadership of the ITP, he is a Professor of Pathology at the University of Michigan and directs the Paul Glenn Center for Aging Research.

In an interview with  journalist Arkadi Mazin, Dr. Miller acknowledges that many drugs that work in mice do not work in humans, but that it’s “silly” to argue that none would work in humans if tested, he says. He points out that most of the drugs developed for therapeutic effect in people were initially discovered by working on mice and rats, and anticipates that some day soon a drug that will extend life in mice will do so in humans as well.

 

Longevity Drugs — Peter Attia Interviews Richard Miller

Peter Attia, MD is a physician focused on the applied science of longevity. His practice deals extensively with nutritional interventions, exercise physiology, sleep physiology, emotional and mental health, and pharmacology to increase lifespan (how long you live), while simultaneously improving healthspan (the quality of your life).

Dr. Attia also has an impressively informative podcast, which the following interview with Dr. Richard Miller underscores. (Scroll down to listen.)

At time stamp 1:55:30 Peter and Richard express their bottom line takeaway.

Rich Miller’s basic takeaway:

• Some drugs can expand lifespan by slowing aging
• Some drugs work even when started in middle age
• Some drugs work in one gender, not the other

Peter Attia’s basic takeaway:

• mTOR matters
• Low glucose is better than more
• Sex specific hormones do something positive

Topics discussed with relevant time stamps:

• Dr. Miller’s interest in aging, and how Hayflick’s hypothesis skewed aging research (3:45)
• Dispelling the myth that aging can’t be slowed (15:00)
• The Interventions Testing Program—A scientific framework for testing whether drugs extend lifespan in mice (29:00)
• Testing aspirin in the first ITP cohort (38:45)
• Rapamycin: results from ITP studies, dosing considerations, and what it tells us about early- vs. late-life interventions (44:45)
• Acarbose as a potential longevity agent by virtue of its ability to block peak glucose levels (1:07:15)
• Resveratrol: why it received so much attention as a longevity agent, and the takeaways from the negative results of the ITP study (1:15:45)
• The value in negative findings: ITP studies of green tea extract, methylene blue, curcumin, and more (1:24:15)
• 17α-Estradiol: lifespan effects in male mice, and sex-specific effects of different interventions (1:27:00)
• Testing ursolic acid and hydrogen sulfide: rationale and preliminary results (1:33:15);
• Canagliflozin (an SGLT2 inhibitor): exploring the impressive lifespan results in male mice (1:35:45)
• The failure of metformin: reconciling negative results of the ITP with data in human studies (1:42:30)
• Nicotinamide riboside: insights from the negative results of the ITP study (1:48:45)
• The three most important takeaways from the ITP studies (1:55:30)
• Philosophies on studying the aging process: best model organisms, when to start interventions, which questions to ask, and more (1:59:30)