Fight Aging!

Osiris Green is a new clinical services business just getting underway, offering assessment of a DNA methylation biomarker of aging as a consumer product. For the customer it works much like the established consumer services for DNA sequencing that look at alleles and single nucleotide polymorphisms, such as 23andme, in that you send off a saliva sample and get back the results. DNA methylation is one of the forms of epigenetic decoration that controls the pace at which proteins are produced from their genetic blueprints, these markers constantly changing in every cell in response to circumstances and environment. For some years now patterns of DNA methylation have looked very promising as the foundation for a biomarker of aging, a way to assess biological age rather than chronological age. We age because we accumulate forms of cell and tissue damage that occur due to the normal operation of metabolism. That damage then spirals out to cause the wide variety of age-related diseases and disability, but at the base of it all we all age in the same fundamental way and for the same reasons, albeit at slightly difference paces due to our different choices and experiences. Therefore we all share the same cellular reactions to damage, and two people with much the same damage load and degree of aging should have quite similar DNA methylation patterns for at least some genes, there to be picked out from the noise of other changes.

A good biomarker of aging is an important component for the near future development of rejuvenation therapies, such as the senescent cell clearance treatments presently under development. Researchers can evaluate the effectiveness of senescent cell clearance in terms of proportion of these unwanted cells removed, and, based on the evidence showing cellular senescence to contribute to aging and age-related disease, expect to find that long-term health is improved. But how to then determine the results in terms of years of life expectancy gained as a result of that treatment? The only existing approach is to wait and see, which is expensive and time-consuming in animal studies, and out of the question for human trials. A biomarker for biological age that can be applied immediately before and immediately after an alleged rejuvenation treatment changes the entire picture of development, however. It enables a far more rapid assessment of therapies and lines of research, speeding up progress towards effective clinical treatments for the causes of aging. This is why I'm most pleased to see progress towards offering DNA methylation biomarker implementations as a paid service. Commercial development is an important part of breaking this technology out of the laboratory, getting more human data, trying different patterns, and settling upon the optimal set of genes to evaluate. I recently had the chance to talk to Neil Copes at Osiris Green and ask a few questions about this initiative and his thoughts on the industry:

Who is Osiris Green? How did you get together and decide that this was the thing to be doing in this new industry?

Currently, Osiris Green Inc. is myself and Dr. Clare-Anne Canfield, who I've known now for over two decades. Osiris Green really began in 2003 when she and I decided that extending human lifespan was the most important thing that we should be working on. We enrolled at the University of South Florida and earned our PhD's in Cell, Molecular, and Microbiology because of that decision. We officially started the company then after we graduated. By the way, the name Osiris Green isn't just a reference to Osiris, the green-faced Egyptian god of resurrection and regeneration. It's also a reference to a chapter titled "The Green Face of Osiris" in Dr. Michael West's 2003 book "The Immortal Cell," which is actually part of what initially inspired us to pursue lifespan extension in the first place.

The company began with the idea of providing customers with ways to measure various biological parameters that might correlate well with chronological age. We wanted ways for people to easily monitor their own aging at the cell and molecular level, with the idea being that these services could help in evaluating different antiaging therapies. Also, we liked the idea of building databases of anonymized user data that could let people match lifestyle parameters (diet, exercise, etc.) to trends in the molecular results. We began putting together protocols for proteomic and metabolomic profiling of blood and saliva (which closely mirrors the molecular contents of blood). We eventually developed a saliva-based proteomic profiling assay, but the cost for a single test - $200 to $500 depending on the depth of the analysis - seemed pretty prohibitive for most customers. Dr. Canfield and I started looking for faster and cheaper alternatives, which is when we began playing around with ideas for measuring gene promoter methylation. In the end I think it was a fortunate switch - DNA methylation states tend to have a tighter correlation to chronological age than other parameters, as detailed by all the excellent work coming from Steve Horvath.

How did you settle on the particular combination of genes you are testing?

We wanted a method that would be cheaper than using a genome-wide analysis or working with microarrays. I remembered a 2011 paper from Eric Vilain's lab linking chronological age with a fairly linear trend in methylation in the promoters of a small set of genes. We did a test run using just the TOM1L1 and NPTX2 promoters, which were among the top genes in the paper and fairly easy to work with from a technical standpoint. The initial results looked good so we developed the service from there.

You are forging ahead with your own implementation of part of the Horvath approach to epigenetic age; how are you validating it?

We're still a fairly small operation. So far validation has consisted of getting as much saliva as we could from friends and family members, and processing the samples. We then used CpG methylation and known chronological ages to calibrate our model. So far the linear model is estimating samples with an error of 7 years standard deviation from chronological age. The idea then is to continue performing estimates on paid samples and refining the model as necessary, even providing new estimates on older samples so that users can continue to get any refinements to their existing data as time goes on.

The Horvath and Hannum DNA methylation results have been out there for a while now. Why do you think it took so long for efforts like Osiris Green to emerge?

Because we're just now at a point as a species where real life extension is becoming a technological possibility. As such, public interest in life extension is slowly coming around. In 2003 when Dr. Canfield and I started working on our goal, the number of researchers in the field seemed disturbingly low. Since then, a decent amount of talent and funding has started flowing into lifespan research, due both to the advancing technology and to the efforts of people like Dr. Aubrey de Grey to bring awareness to the field. If this trend continues, I imagine the number of similar services as ours - and of life extension oriented companies in general - will only increase. Regardless of what happens with Osiris Green, I find it comforting that so many people and companies are now working on the problem in earnest.

Where do you see this broader field of rejuvenation research going over the next decade? Where does Osiris Green fit in to this picture?

I suspect that we'll see more clinical applications of the life extension technologies that are currently emerging. Human aging is a multifaceted problem, so the various ways to attack it are going to be diverse. I'm hoping to see things emerge like clinical trials of thymic regeneration coupled with immune system resets to eradicate anergic T cells; more and more senolytic drugs developed along with effective treatment regimens; and finally some useful age-breaker drugs making their way to market. Honestly, I'm in this for the long-haul, so I'm hoping to mold Osiris Green to help and provide services in any way that I can. In the short term, I'd like to simply expand the range of age-related markers that we can measure for customers, and to provide better and better resources for people interested in human aging.

If this works really well, and Osiris Green is flooded with customers, what is the next mountain to climb?

Oddly enough, Dr. Canfield and I have recently become fairly interested in the study of long-lived animals. Short-lived organisms, like C. elegans and Drosophila are cheap and easy to work with in a lab environment, and they make for quick experiments, but honestly they're bad models for longer-lived organisms like humans. Researchers are using these short-lived animals in an effort to extend human lives, but nature has already found ways for vertebrates to live longer natural lifespans than us. Dr. Canfield actually just finished writing a book that's a survey of the world's long-lived organisms, and the list of creatures that are relatively close to us evolutionarily is longer than most people realize. This list even includes animals like the American alligator and many species of turtle that are easily accessible in central Florida where we are located. We're currently involved with setting up a nonprofit organization for the study and conservation of long-lived species, and we're hoping that we can apply some of what we've learned from Osiris Green to build DNA methylation models for developing nonlethal ways to assess animal lifespans in the wild.