Q. What does Tony Blair’s reading list and the Longevity.Technology team’s have in common?
A. Dr David Sinclair’s book: Lifespan: Why We Age – and Why We Don’t Have To.
David A Sinclair, PhD, AO is a Professor in the Department of Genetics and co-Director of the Paul F Glenn Center for the Biology of Aging at Harvard Medical School. He is best known for his work on understanding why we age and how to slow its effects. Dr Sinclair is co-founder of several biotechnology companies (Sirtris, Ovascience, Genocea, Cohbar, MetroBiotech, ArcBio, Liberty Biosecurity) and is on the boards of several others.
Ahead of tomorrow’s Metabesity 2019 2-day conference, where Dr Sinclair is presenting, we sat down for a chat with one of Longevity’s most high-profile innovators.
Longevity.Technology: Why did you write your book now?
David Sinclair: I wrote my book to start the discussion about aging being something that is a medical condition that’s treatable. It’s not going to happen tomorrow, drugs are not going to be marketed ever as an aging treatment, unless aging itself is considered disease by the FDA.
I feel like I’ve blowing a paper boat across the ocean and finally I’ve got some wind behind me. There are many other people pushing hard and I can’t take credit for the whole movement, but I do think it’s been helpful that I’m usually the one that sticks his neck out.
Writing the book would have been quicker if I hadn’t rewritten it about three times over 10 years because the research kept going so quickly. And what I learned, actually was write it down as it’s happening in your lab.
Longevity.Technology: There are detractors that don’t consider Longevity to be a thing, what would you say to them?
David Sinclair: There will be an evolution where doctors increasingly become comfortable prescribing medicines to prevent diseases, rather than wait until they actually occur.
And Metformin is leading that way, a lot more people are aware of Metformin as a potential Longevity drug. And I don’t know if this is true, but they’ve told me the sales of Metformin have gone up in the US since I’ve been running around talking about it. Every every day I have people write to me saying, who can give this to me?
Longevity.Technology: You mentioned the FDA earlier as a gatekeeper to recognising aging as a disease, we’ve heard positive things about US policy making, what’s your experience?
David Sinclair: Felipe Sierra [Director of the Division of Aging Biology at the National Institute on Aging, NIH] has been a real force coining the term gyroscience, or at least promoting it. It’s great to see that they’re looking more forward rather than they used to.
I think that NIA [National Institute on Aging] has done a really great service to the field, funding areas that are underrepresented and you usually don’t think of the government as being innovative, but the NIA has been recently.
Longevity.Technology: There is a lot of crossover now with what’s happening in terms of AI and discovery? Are you employing any of those techniques with with with your work at the moment?
David Sinclair: Yes we are [using AI] and it extends to everything within our biology, from infectious disease detection and blood tests, through to genomics, which is looking at the three dimensional structure of the nucleus and our DNA, this is very important for aging among other diseases like cancer.
And because we think that aging is largely driven by epigenetic changes these technologies are extremely important to us. The only way to crunch that amount of data is to use modern bioinformatic technologies that are always advancing. We’re able to use machine learning to reduce the guesswork in drug development.
Longevity.Technology: Do you think the Longevity sector should be establishing a broad set of biomarkers that everybody’s working from?
David Sinclair: People have been talking about that for 20 years, and it hasn’t gone very far. Fortunately we’re finally getting there with humans and mice with a reliable frailty index [1].
We have biochemical blood test markers that are correlating with longevity, morbidity and mortality. And then I think the Horvath Clock has been a real breakthrough, too, because it’s not just about things that changed over time, but more a true predictive clock that I believe is tied into the actual aging process.
Longevity.Technology: Take us into where your research sits now?
David Sinclair: My latest work is focused on epigenetic reprogramming. And In our case, we’re going to try to reverse glaucoma. We think that aging is largely driven by epigenetic changes, structures in the nucleus that change over time, these technologies are extremely important to us.
Longevity.Technology: What are you working on that’s exciting?
David Sinclair: I’m most excited about the reprogramming of a cell with the ability to reset it and do so in a safe manner. I’m seeing things in our animals that I didn’t think I’d ever see. I didn’t know, there was a backup hard drive of the epigenome [2], which apparently exists.
And we’re just learning how to reset that and reinstall the software, so to speak. We’ve gone from one graduate student working on this to half my lab working on this in the past year. That’s how exciting it is.
Longevity.Technology: Sinclair’s work on partial cellular reprogramming gains some of its inspiration from the work done by Juan Carlos Belmonte at the Salk Institute, who showed that adult cells could be induced back to a pluripotent stage of their development. This revelation is profound for those who want to turn back the cellular clock, but presented the problem that embryonic cells inside of an adult body could easily become cancerous.
Sinclair’s team are instead doing research into partial cellular programming, instead choosing to revert cells to expressing the pattern of genes they expressed while they were younger (with cellular aging emerging from the fact that cells lose this useful pattern, and see the introduction of noisy elements — such as genes that shouldn’t be expressed in them — as they grow older). Their focus right now has seen them produce some fascinating pre-print results into restoring vision in the retina [3].
