An exclusive with AgeX Therapeutics CEO Dr Michael West looks at the puzzle of aging.

AgeX Therapeutics is an American biotechnology developing novel therapeutics that works on addressing human Longevity. The company was founded in 2017 by Dr Michael D West with backing from Juvenescence founder Jim Mellon.

Dr Michael West connected with Longevity.Technology to discuss aging research, the Longevity field and the latest therapies at AgeX Therapeutics.

Longevity.Technology:  What got you into aging research? You’ve got to tell us what drove you on, was there a single lightbulb moment? A series of converging realisations?
Michael West:  Absolutely. There was a very defined moment. It completely changed my life, actually. Still, it isn’t easy to put in just a few words. Let me just say that after a decade-long search for meaning in life, I came to realize that all that humans hold dear, the lives of our loved ones, the beauty and meaning we so often take for granted in our lives, will ultimately be annihilated in our personal death. I came to see aging and death as the last great enemy to be conquered. And I saw the effort to understand and alter the course of aging as not only a noble (albeit challenging) quest, but also a delightful puzzle.

I don’t know about you, but I love the challenge of solving mysteries. Aging is almost certainly the greatest medical mystery we have ever faced. I found the quest to understand and intervene in aging an absolutely exhilarating challenge.

Longevity.Technology: So you have a number of development-stage therapeutics sitting in the preclinical stages, which ones would you say will be the fastest at reaching the market?
Michael West: It’s always difficult to predict the pace of product development in biotech. Let me start with the good news. We now know enough about aging that we can design new products that we believe will have an unprecedented impact on aging. In other words, much of the hard work of getting down to the level of the clockwork mechanisms of aging and learning to turn back the clock has now been worked out in the laboratory. For instance, it is now a routine procedure to reverse the aging of human cells in the laboratory dish. So, the application of these technologies to people, not just cells, is the step we are talking about. So there are a couple of products we are developing to accomplish this:

The first is our induced Tissue Regeneration (iTR) program. Aging, and in turn diseases of old age, are due to two characteristics that are present in the cells in our body when it is first forming but that are lost with time. The first is the replicative immortality of cells, and the second is the ability of tissues in our body to regenerate. So, during the course of what we call development, the cells in our body become mortal (that is, they have a finite lifespan), and tissues and organs in our body, if damaged, lose the the ability to repair themselves.

In some animals, one or both of these properties never get shut off. You may have heard of the Mexican salamander. Lob a leg off this animal and it grows back perfectly. If animals retain both cell Immortality and regenerative potential, they generally don’t age at all. So, we think the biology behind these processes are fundamental to aging.

Back in 2010, when I was CEO of BioTime, Inc (now Lineage Cell Therapeutics) we began work to see if cell aging could be reversed back to this regenerative state. We’ve made considerable progress since that time, working to optimize a potential pharmaceutical preparation to reverse the aging of human tissues and thereby restore regenerative potential: our iTR program. I’m more optimistic about iTR than anything I’ve worked on to date.

The second is our UniverCyte platform. The whole field of regenerative medicine – and Longevity, by extension – could make huge strides if we could find a way to reliably engineer a means of making young cells of any kind to repair tissues in the body worn out with age. To be cost-effective, ideally those young replacement cells could be engineered so as not to be rejected as foreign. That is the science of UniverCyte.

In other words, we are developing a technology to manufacture cells that can be made available off the shelf (or as some say, allogeneic). We plan to make our own regenerative products such as AgeX-VASC1 and AgeX-BAT1 using the technology as well as partner the technology with other companies for the many different applications in medicine.

“Aging is almost certainly the greatest medical mystery we have ever faced.”

Longevity.Technology: Another side of your work involves going into partnership with companies that need your purestem cell lines for their research. Is this up and running?
Michael West: Right, PureStem is another important technology we developed that has application in manufacturing potentially hundreds of the diverse cell types that make up the human body. Biotech and large pharmaceutical companies are really gearing up to use pluripotency to make the whole new class of cell-based products in regenerative medicine.

Of primary concern is the purity of the cells in these new products. PureStem allows the scalable manufacture of monoclonally-purified regenerative progenitor cell lines that are suitable for off-the-shelf use for researchers. This platform is designed to work in concert with our UniverCyte platform.

Longevity.Technology: How do you see recent developments in US stem cell research affecting AgeX?
Michael West: There are some clear trends. Progress with what are called “adult stem cells” have been disappointing and there have been a large number of failures in companies attempting to develop such products. Adult stem cells are often more challenging to scale-up, and generally lack the regenerative properties I mentioned earlier. So, there is a clear trend to pluripotent stem cell-based manufacture. One indication of this are the recent acquisition of companies in the space by large biotech and Pharma.

Longevity.Technology: There have also been recent eases in regulation in Japan, is there a potential for stem cell research to move east?
Michael West:  Yes, the concept of progressive approval is being implemented in Japan and is seriously being considered by countries around the world. The concept is that the tsunami of age-related degenerative diseases and their associated costs are swamping our health care systems, and severely straining the economies of many industrialized countries.

So progressive approval allows innovative cell-based regenerative products to be provisionally licensed for sale once safety has been demonstrated. If the product doesn’t prove efficacious thereafter that license is revoked. The theory is that this will accelerate beneficial and cost-saving therapies for aging. I agree with the concept in principle.

Longevity.Technology: At the time of this conversation, there’s only one induced pluripotent stem cell therapy approved for testing in humans. Does this represent the first snowflake in an avalanche, or are there some significant technical challenges involved before we can begin to see induced pluripotent stem cells being used in and human therapies?
Michael West: There are several kinds of pluripotent stem cells (the cells that can make all the young cell types in the body). Embryonic Stem (ES cells) are really the gold standard in my opinion, because they are the most normal. There is another type called “induced Pluripotent Stem (iPS) cell. These are cells from the body, such as skin cells that have been taken back in time to behave like ES cells. However, we and others see what are potentially serious abnormalities in iPS cells. We see, for instance, hundreds of abnormalities in the DNA, in what is called the “epigenome.” Since patient safety is always the number one concern, I am of the opinion that ES cells will be increasingly seen as the best choice for product development.

“…for the first time in history, scientists know how to target new therapies at aging itself, a prospect that would have resoundingly been labelled as science fiction just 20 years ago.”

Longevity.Technology:  You also appeared at the US Metabesity 2019 Conference. Are there any specific solutions to the Metabesity crisis you can see regenerative stem cell therapy playing into?
Michael West: Yes, at AgeX we specifically target “metabesity” with AGEX-BAT1, our cell therapy product candidate: brown adipocytes (brown fat cells) for the treatment of Type II diabetes and age-related metabolic disorders. We lose activity in these cells rather dramatically as we age and scientists believe that adding them back may help restore the youthful metabolism we once had when we were young.

Longevity.Technology: Where do you see the longevity industry heading to in the next ten years?
Michael West: The longevity biotechnology industry is really starting to hit its stride, as evidenced by accelerating pace or really significant scientific publications in the field. You also see this in the explosive increase in new biotech companies targeting the biology of aging. I believe all this reflects that for the first time in history, scientists know how to target new therapies at aging itself, a prospect that would have resoundingly been labelled as science fiction just 20 years ago.

If research funding is adequate (and that is probably the biggest “if”!) I could see the industry making real strides in the next decade, bringing a variety of treatments and even cures for age-related degenerative diseases to the clinic.

By the end of the decade, say 2029, such treatments may even start to have a noticeable effect on the long tail of life span statistics (in other words, effecting a small proportion of the elderly population) and reaching the bulk of elderly Americans in the next decade or two after that.

It is my firm hope and belief that it is well within our means to affect a “hockey stick” graph on average lifespan. At the end of the next decade we should start to see data that hints in that direction.

These advances could save countless lives, alleviate a tidal wave of suffering worldwide, but also provide a huge boost to the economy. We could prevent entitlement spending related to the demographic age wave and associated chronic degenerative disease from subsuming the entire economy, and thereby avoid fiscal catastrophe.

From a glass half full perspective, too, imagine the economic trend lines if the average American worker could start to see his or her health span extended enough to continue working and contributing for even an extra two or three years. Economists predict that rather than increasing health care expenditures, it could decrease them dramatically, and, of course, improve the quality of life for our loved ones. I think that we can start to move in that direction in the next decade or so, but the factor that will determine whether these advances occur in our lifetimes are completely dependent on that “if”. If a sufficient number of scientists and technicians are assembled for the task, we can clearly make the world a far better place.