How will your research contribute to extending healthy human life?
The field of Geroscience is on the cusp of having the first translational interventions to promote healthy longevity in people. Efforts underway in my work to advance both basic and translational Geroscience. On the translational side, I am currently leading the first veterinary clinical trial to promote healthy longevity in middle-aged companion dogs (www.dogagingproject.com), and I believe that successful completion of studies like this will set the stage for similar studies in people.
Simultaneously, my lab is developing and optimizing new intervention strategies in mouse models. These include optimization of strategies for transient treatment with known pro-longevity compounds such as mTOR inhibitors and alpha-glucosidase inhibitors in mice. At the time of this writing, for example, we have developed a single transient treatment regimen with the mTOR inhibitor rapamycin that is sufficient to increase life expectancy in middle-aged mice by more than 50%. I believe that transient, mid-life intervention strategies have a much greater translational potential for human use compared to the lifelong treatment approaches that have been primarily tested in the past.
On the basic science side, my lab continues to identify and characterize novel targets for promoting healthy longevity, such as our recent report in Science showing that a single flavin-containing monooxygenase is both necessary and sufficient to promote lifespan and healthspan extension in C. elegans downstream of three genetically distinct longevity pathways. We also have projects in the lab studying the role of the microbiome in healthy longevity, and we are working to understand the interaction between individual genetic makeup and the response to longevity interventions such as dietary restriction in order to begin to move the field toward truly Personalized Geroscience.
What were the major breakthroughs made by your laboratory or companies?
<li>identification of mTOR as a central longevity regulator downstream of dietary restriction (Kaeberlein et al., Science, 2005)</li>
<li>the first identification of the hypoxic response as a major pro-longevity pathway (Mehta et al, Science 2009)</li>
<li>the first demonstration that inhibition of mTOR by rapamycin can impact mitochondrial function and alleviate severe mitochondrial disease (Johnson et al, Science 2013)</li>
<li>discovery of flavin-containing monooxygenases as a conserved downstream target of the hypoxic response, dietary restriction, and mitochondrial longevity pathways in C. elegans (Leiser et al, Science 2015)</li>
<li>major contributions to sirtuin biology, including the first paper showing that activation of a sirtuin can extend lifespan (Kaeberlein et al. Genes Dev 1999), the first paper dissociating sirtuins from dietary restriction (Kaeberlein et al, PLoS Biol 2004), and the first paper demonstrating that resveratrol is a substrate-specific activator of sirtuins (Kaeberlein et al., JBC, 2004) </li>
Can your research be commercialized in the future and is there any way to invest in this research today?
Absolutely. We are developing IP in several areas.
<li>Commercialization of a canine healthy aging treatment or dog food based on clinical data from our ongoing and planned veterinary clinical trials with mTOR inhibitors and alpha-glucosidase inhibitors</li>
<li>Utilization of our short-lived mitochondrial disease mouse model to identify bioactive drugs (both pharmaceutical and natural product) with beneficial effects on mitochondrial function and healthy aging.</li>
<li>Drug development assays to identify flavin-containing monooxygenase activators.</li>
<li>Cell based assays to identify novel mTOR inhibitors<br>
In your opinion, what are the most promising companies contributing to longevity research today?
Companies have, thus far, had relatively little impact on the scientific advances in the field and it’s somewhat unclear which of the current companies are likely to contribute to the quality and pace of research in Geroscience. Calico obviously has great promise in this area based on the large amount of funding and the quality of some of the people they have brought onto their team, but has not been active long enough to have made an impact yet. Novartis should be considered to be at the front of companies taking a true translational approach to Geroscience, as indicated by their work on mTOR inhibitors to rejuvenate the aged immune system in otherwise healthy people. There are several small biotech companies with interesting IP related to pre-clinical studies on potential longevity interventions, but much of this is untested and unproven in people and, in some cases, based on rather limited pre-clinical data.
Do you think there will be significant breakthroughs in longevity research in the next decade?
Absolutely. The pace of advancements in Geroscience research is clearly accelerating, despite stagnant funding in the U.S. The field has undergone major advances in the past decade and I have no doubt that the advances will be much greater in the next decade, particularly in the translational arena.
I expect that we will have validation of at least one intervention as highly likely to promote healthy longevity in people based on veterinary clinical studies where a treatment has been shown to extend healthy longevity of middle-aged pet dogs. This could happen as soon as 3 years from now with a product on the market shortly thereafter if sufficient funding is allocated to this goal.
If things go well with the TAME trial or similar approaches, we may also have preliminary indications that metformin or another drug can delay co-morbidity in people.
Regenerative approaches and stem cell therapies continue to appear promising and there will also likely be translational applications in stem cell therapies for promoting healthspan, although the impact on longevity from such treatments is less clear with little evidence that it is possible to extend lifespan in this way.
Do you think it is a good time for iVAO to get into longevity business and invest in biotechnology in general?
That depends on your goals, vision, and the scientific knowledge of your team. In terms of impact, now is a fantastic time to invest in Geroscience for all the reasons described in my answers above. From a financial perspective, I also believe that this is an outstanding time to invest in Geroscience, but you will need to be smart about how you do it. There are a few areas that have the potential for large profits and rigorous data to suggest a high likelihood of success, but there are also several areas where the quality of the data is less impressive than how the story is being presented. Lessons can be learned from past failures in this area, and it will be critical to have the highest quality scientific partners and advisors on your team. If you invest in the longevity business, my advice would be to partner with researchers who have a proven track record of important contributions to the field of Geroscience, a reputation for doing high quality science, and a broad understanding of the biology of aging.
Can you say a few words about the upcoming conference in St. Petersburg? What are your expectations?
I attended the conference in Sochi a few years ago, and it was a fantastic experience, both in terms of the opportunity to visit Russia for the first time and the scientific quality of the meeting. I expect the St. Petersburg meeting to even exceed the Sochi conference. The quality of the invited speakers is truly outstanding and, of course, St. Petersburg is an amazing location in which to hold the conference.