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Matt recently exchanged a lively correspondence about biological age with Harold Katcher, cofounder of a stealth biotechnology company and inventor of E5. E5 is a compound consisting of the purified exosome fraction of blood from young piglets—in other words, young pig blood. Harold recently co-published a paper suggesting that injecting this young pig blood into rats made rats younger on several biological aging measures, including inflammatory markers and epigenetic aging signatures. Indeed, Harold has injected E5 into his own right hand and presented differences in the appearance of his right and left hands on social media.

Putting pig blood into other animals (and into ourselves!) to reverse biological age might seem like a crazy thing to do. But this idea actually stems from a methodology with a decades-long history called heterochronic parabiosis, an area of research that explores the effects of joining the circulatory systems of different-aged organisms. In this experimental technique, researchers surgically connect two animals, typically mice, of disparate ages so that they share a common bloodstream. This union leads the older and younger individuals to exchange not just blood cells but also signaling molecules, growth factors, and other circulating factors. Remarkably, when an older animal is paired with a younger counterpart, it often experiences improvements in various aspects of health and tissue function, while the younger partner may exhibit corresponding signs of accelerated aging. The mechanisms underlying these effects are complex, multifaceted, and very much still under investigation.

In this episode, Matt takes a magnifying glass to E5: what we know about the compound, how it affects lifespan, and how its impact on lifespan stacks up with that of other longevity inventions such as caloric restriction and rapamycin. He discusses whether Harold's recent paper truly proves a reversal of biological age and where his findings fit into the larger body of literature in the field. He also gives us a window into the methodology of heterochronic parabiosis, what the primary data about life expectancy gains through this intervention show, and whether heterochronic parabiosis-inspired interventions such as E5 are realistic approaches to human lifespan extension.

0:00 Trailer
0:45 Introduction
2:37 A primer on E5 and the origins of the idea
10:00 Primary data on life expectancy in heterochronic parabionts
13:35 Interpretations of ideas from heterochronic parabiosis
19:37 What we know about E5
23:34 The effects of E5 on lifespan
25:51 How impressive is Sima's long lifespan + how does the lifespan extension of E5 stack up against that of other experiments?
35:14 What we can conclude from the E5 data so far?
36:00 Reversal of biological age in multiple rat organs by young porcine plasma fraction
45:30 Is the E5 model a pragmatic/scalable approach to lifespan extension?
49:04 Wrapping up

Producers: Tara Mei, Nicholas Arapis
Video Editor: Jacob Keliikoa

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https://www.optispan.life/

Hi, I'm Matt Kaeberlein. I spent the first few decades of my career doing scientific research into the biology of aging, trying to understand the finer details of how humans age in order to facilitate translational interventions that promote healthspan and improve quality of life. Now I want to take some of that knowledge out of the lab and into the hands of people who can really use it.