In his new book The Illusion of Knowledge, author Harold Katcher draws a bold thesis that if proven out to be correct could send shockwaves through the human longevity research field. It would certainly be a paradigm shift in how we think about cellular aging in many ways.
The main claim being that individual cells in our bodies don’t age because of an inherent internal clock rather because of various pro-aging factors present in blood plasma that surround those cells and signal them to behave aged. Dr. Katcher postulates that cells don’t age on their own but rather are driven by biological clock of the organism’s internal ecosystem (which can be controlled).
The results of his experiment show 2-year old rats (60-year old human equivalent) being reset in terms of age biomarkers (DNA methylation) to that of a 6-month old rat.
In short, it is proposed that young factors present in blood plasma, in mammals at least, control the age phenotype at the cellular level. Dr Katcher created young blood plasma product called E5. Injecting E5 resets the cell age which then lowers tissue age and brings organ/organism age phenotype back to youthful level. Sounds too good to be true? The experiment is currently being repeated by an external, independent lab. Extraordinary results call for extraordinary verification measures.
In his book, Dr. Katcher goes further into explaining his theory of aging, to try to answer the following question -- if aging is programmed into us on systemic level, why is that? Why did human species evolve to live a certain amount of time. Well, he again posits that aging is programmed into our bodies on a higher level than cells (and therefore DNA). There's a cycle to our lives, growth, reproduction age and post-reproduction phase, and eventually death, driven by evolutionary forces of energy conservation and preservation of species as primary goal. However there's nothing physical about this process that would not allow us to reverse it with enough understanding. We've evolved naturally (on Earth) over millions of years under set circumstances - set gravity force, a 24 hour day and night cycle and therefore developed our circadian rhythm, etc. What were to happen if we changed / lengthen those cycles? If day / night period would last more than 24 hours on another planet (or under artificial setting). In a lab experiment on Mouse Lemurs when the day/night cycle was sped up they subsequently aged faster, leading to believe our aging is directly tied to such periodic cycles. And influencing those can be one way to alter the rate of aging.
At this point at the lab in Mumbai, Dr. Katcher and his team has run the E5 injection experiment multiple times on 2-year old rats injecting it into their veins - 4 injections once every other day, with the procedure being repeated 90 days thereafter.
Several biological age predicting markers, tested via DNA methylation assay developed by Steve Horvath specifically tuned for rats (results published in preprint paper: https://www.biorxiv.org/...v1) drop and continuously fall post injection (and subsequent 2nd series of injections at day 90) to reach levels similar to those seen in 6-month old counterparts, at about 150 days after first injection. Independently, Dr. Katcher took measurement of several markers such as grip strength, cognitive perception that reach similar indications to Horvath’s clock results. Some of the treated rats were sacrificed and their organs dissected with deep tissue DNA methylation and photographic measurements taken. The examined organs (brain, heart, lung, liver) confirmed findings of youthful biomarkers resembling those of 6-month rats. Only exception being the hippocampus where the rate of change takes longer but eventually seemed to converge with youth counterparts at 150 days post first injection. However, it raises questions on the effectiveness of the product when examining brain tissue vs. other organs in rats’ bodies.
One additional finding to note is considerable drop in the number of senescent cells observed in the treated rats (vs. the control group).
Salient quote from the paper:
“First, the rat pan-tissue clock re-affirms the implication of the human pan-tissue clock, which is that aging might be a coordinated biological process that is harmonized throughout the body. Given that the circulatory system irrigates and connects all the organs, it is more likely than not, that the regulation and harmonization of age are mediated systemically.
The book is written in an easy to digest style. Kutcher is intertwining explanations of scientific concepts that lead to his discovery with short essays from his life illustrating the winding path that takes him to ultimately make the discovery of E5 (E stands for elixir, and 5 being a lucky number picked by one of his collaborators).
It is also interesting to read about Dr. Katcher’s interactions with various luminaries in the anti-aging field, as an outsider (with no monetary backing) receiving a (deserved?) push back, then finding a financier unconnected to the longevity world to realize his experiments.
In his book Dr. Katcher also makes a small note about his experiences with Rapamycin, outlining his take on the limited potential of intervening in nutrient sensing pathways of cells.
It is unclear at this stage what E5 specifically contains but it appears to be a mix of various blood plasma youth promoting factors. It appears to include GDF-11 (as Harold mentions it in one of his interviews) among many others. While we wait for the specifics to be revealed as Dr. Katcher and co. (Nugenics Research) await patent issuance, they are planning to repeat the experiments in dogs (in collaboration with Greg Fahy).
With Steve Perry’s work and experiments with GDF-11 alone showing promising results in dogs it will be interesting to see what E5 brings to the table.
P.S. David Sinclair’s commentary on the initial publication of results:
