Gut Microbiome's Role in Aging and Longevity Interventions

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• Microbiome Longevity Connection
• Bacterial Communication with Body
• Interventions and Microbiome Changes
• Alpha-Ketoglutarate Anti-inflammatory Effects
• Research Examples in Aging
• Full Transcript

Microbiome Longevity Connection

The gut microbiome is a critical factor in the human aging process. Dr. Brian Kennedy, MD, emphasizes that the body is a reservoir of bacteria, with estimates of up to 10 times more bacterial cells than human cells. This complex ecosystem of organisms living together directly influences longevity. The conversation between gut microbes and mitochondria is a key area of scientific interest. Dr. Brian Kennedy, MD, explains that ignoring this relationship is naive when studying aging or potential interventions.

Bacterial Communication with Body

Bacteria located in the gut, saliva, and on the skin are in constant communication with the rest of the body. Dr. Brian Kennedy, MD, states that this dialogue influences behavior and overall health. A substantial body of data shows the microbiome affects the immune system and cognitive function. These effects are fundamental to understanding systemic health. Dr. Anton Titov, MD, and Dr. Kennedy discuss the need to always keep the microbiome in the equation.

Interventions and Microbiome Changes

Many interventions known to extend lifespan also cause significant alterations to the gut microbiome. Dr. Brian Kennedy, MD, points out that any swallowed pill is encountered by gut bacteria first. Researchers are actively trying to understand if these microbial changes are essential for the observed longevity effects. A common theme is that these interventions often revert the microbiome to a more youthful state. Dr. Kennedy strongly suspects these changes have important signaling effects on the body's rate of aging.

Alpha-Ketoglutarate Anti-inflammatory Effects

Metabolites like alpha-ketoglutarate (AKG) are used by bacteria and can have profound health impacts. Dr. Brian Kennedy, MD, uses AKG as a prime example of a compound that requires a dual consideration. Scientists must think about what it does to human cells and how it influences the microbiome. This influence could create a secondary effect on health and aging. Dr. Brian Kennedy, MD, notes that AKG and rapamycin are very anti-inflammatory, potentially by suppressing inflammatory signals from the gut.

Research Examples in Aging

Research in model organisms provides clear examples of the microbiome's direct effect on lifespan. Dr. Brian Kennedy, MD, references work in worms where gut bacteria actually shorten the organism's lifespan. Killing these bacteria allows the worms to live longer, despite them being a food source. In more complex mammals like mice and humans, the microbiome consists of thousands of different species. While direct effects are harder to pinpoint, Dr. Kennedy is confident these changes are relevant to healthy aging.

Full Transcript

Dr. Brian Kennedy, MD: Microbiome and longevity—that's another big topic. How gut microbes talk to mitochondria, and who or what else the gut microbiome talks to, is important for the aging process.

You can think of your body as a reservoir. Estimates suggest up to 10 times as many bacteria in your body as your own cells. We were naive not to give more thought to that in the past, because we're really a system of many different organisms living together.

It's not surprising that these bacteria in your gut, in your saliva, on your skin, and in other places are talking to the rest of your body and influencing how you behave. There's a lot of data on the microbiome affecting the immune system and cognitive function.

We have to keep that in the equation whenever we're looking at aging or interventions. A number of the interventions that extend lifespan alter the microbiome, so we're trying to understand whether those alterations are important for the longevity effects we see.

If you swallow a pill, the bacteria in your gut see it before you do. We tend to ignore the fact that those pills affect the microbiome.

If you're looking at metabolites like alpha-ketoglutarate (AKG) that bacteria use, you've got to think hard not only about what those things are doing to your body, but how they're influencing the microbiome. That could have a secondary effect on your health or your rate of aging.

Dr. Anton Titov, MD: Is there any other specific example of the microbiome and aging connection that your research showed?

Dr. Brian Kennedy, MD: There are a number of examples from other labs in worms and flies. In worms, the bacteria in the gut shorten the lifespan, and if you kill them, the worm lives longer even though they eat the bacteria. Those are kind of simple issues.

When you look at the human or even mouse microbiome, you've got thousands of different species. I can't point to direct effects of the microbiome, but I strongly suspect that those changes are going to be relevant.

A lot of the interventions that affect lifespan revert the microbiome back to that of a younger person. It would be naive to think that doesn't have important signaling effects on the body.

Probably at least they are reducing inflammation, like we see with alpha-ketoglutarate. I keep using that as an example, but you could use rapamycin as well—it is very anti-inflammatory. It may be because they are suppressing inflammatory signaling from the gut microbiome.