Therapeutic that mimics young plasma could signpost the way to longevity.

We have been keeping tabs on Dr Harold Katcher since May 2020, when the young blood plasma treatment developed by him and his team showed some incredible results in rats.

The results, using Horvath epigenetic clocks, showed an average age reversal across four tissues of 54.2%. Specifically, rejuvenation of liver tissue was measured at 75%, blood at 66%, heart at 57% and hypothalamus at 19%.

Since then Katcher has published a book – The Illusion of Knowledge: The paradigm shift in aging research that shows the way to human rejuvenation – that details the experiment of rejuvenation of rats with the plasma fraction called E5.

Longevity.Technology: Age may be a small word, but it’s a massive concept in longevity – and, it would seem, it’s a lot more than just a number. Maximum lifespan, age decline begins, epigenetic vs chronological age – these are all parts of the language of longevity, a field in which we know asking how old someone is actually a rather complicated question!

Now, it seems, when it comes to rats, the oldest just got older. Rats and mice are very common models for aging research – they are easy to breed, handle and look after, they have a short generation time and their habit and environment can be easily controlled. They suffer from the same diseases and impairments and have provided valuable clues to the key drivers of aging and longevity – however, it seems as though for some rats, we might have to wait a little longer to get results!

Not one to rest on his laurels, Katcher has been putting into practice his interesting concept that the cells’ age depends on the body’s age, and not vice versa. While working at Yuvan Research Inc, Katcher says he has now discovered which part of the blood of young animals controls the age of the whole organism, and has tested this concept by injecting this blood fraction in eight Sprague Dawley 24 months-old female rats.

E5 has its roots in a research paper on heterochronic plasma exchange published in 2013; in it, Katcher notes that plasma of the young appears to contain factors that if injected in the old, can reverse their biological age [5]. Working with a team at Yuvan, a California-based startup that is working on creating rejuvenation treatments, Katcher developed a therapeutic that mimics young plasma. The process for E5 production is patent-pending, and currently Yuvan is planning trials in other species before it can be tested in humans.

“Sima” is the last survivor of the group treated with E5, but the age she has reached – the grand old age of 47 months – allows us, says Katcher to see a path for rejuvenation and perhaps even full control of the aging process.

“Cellular aging is a cell non-autonomous process, which means that cellular aging doesn’t depend on the cell’s history, but on its environment,” states Katcher, who is Chief Scientific Officer of Yuvan.

This experiment is a follow-up the age-reversal in rat tissue experiment of 2020; following Dr Steve Horvath’s preprint indicating that Yuvan’s therapy caused a 54% rejuvenation in male rats according to an epigenetic clock analysis [1], a non-profit based in Belgium, The Healthy Life Extension Society (HEALES), decided to fund two further lifespan studies [2].

The first study used Yuvan’s E5 treatment, and the second study, led by Dr Rodolfo Goya, a biology professor and researcher at the University of La Plata in Argentina, used young rat plasma. 

Goya’s experiment (not yet peer reviewed) achieved moderate life extension in the rats treated with young rat plasma [3]. Yuvan’s experiment with E5 is still ongoing as one of the treated rats, Sima, is still alive at 47 months of age, so far defying the limits of the species’ recorded lifespan.

Didier Coeurnelle, HEALES founder, considers this result very promising, remarking that: “Experiments concerning the lifespan of mice and rats, especially the maximum lifespan, are fundamental for rejuvenation research.”

In addition, Sima, which means means limit, boundary or frontier in Sanskrit, and the other treated rats experienced an intense improvement in grip strength (2.8 times higher than the controls) and general health indicators. According to Goya, who was also one of the authors of the 2020 article: “The muscular strength is a reflection of the prolonged healthspan these animals are enjoying, together with the prolonged lifespan.”

Sima is a Rattus norvegicus, a species of rat with a maximum recorded lifespan of 45.5 months [4] and an average lifespan of between 24 to 36 months. Yuvan’s treatment started to be applied when the rats were already 24 months old and despite the intervention being at ‘middle age’, the maximum lifespan of the species was extended in the treated group, which comprised 8 rats.

So, how does Sima shape up compared with humans? The maximum human lifespan recorded is 122.5 years, but in human years, Sima is already 126 years old. Only further trials will tell if this result can be translated to humans, but this experiment is further proof that aging is malleable.

[1] https://www.biorxiv.org/content/10.1101/2020.05.07.082917v1
[2] https://heales.org/2022/01/03/
[3] https://www.biorxiv.org/content/10.1101/2022.12.01.518747v1
[4] https://genomics.senescence.info/species/entry.php?species=Rattus_norvegicus