#357 ‒ A new era of longevity science: models of aging, human trials of rapamycin, biological clocks, promising compounds, and lifestyle interventions | Brian Kennedy, Ph.D.

Brian’s journey from the Buck Institute to Singapore, and the global evolution of aging research [2:45]

• Brian used to run an institute called the Buck Institute 

Tell folks a little bit about what the Buck is and what you did there 

• It was the first institute solely devoted to understanding aging and longevity, and it started around 2000 with some money that was donated by a woman who died in Marin County north of San Francisco
• Brian was the second CEO there in 2010
• There were about 20 faculty at the time all devoted to either aging or aspects of aging, very basic science
  • As you can imagine in the 2000s at around 2010, that was a significant component of the aging research field 
• It was still a very small field, and so the goal was really to help that institute grow
• It was tough times in the 2010s because the funding levels were low, and it was right before the real interest in aging and longevity happened around 2017, 2018
• So we were really struggling to keep the doors open and the Buck’s doing a lot better now as well as the rest of the aging field 

At the time that you were there, how much of the funding came from NIH and how much came from either donations or industry? 

• It was heavily oriented to NIH and our goal was to get more industry funding
• We started 7 companies when Brian was there, some of which are still hanging around 
• We also really tried to ramp up philanthropy, but philanthropy for aging wasn’t really happening until around 2017, 2018 when people started really getting the idea that you could slow aging and prevent all these diseases and stay healthy and functional

The faculty there are quite the star-studded cast 

• Eric Verdin is there (he came after Brian left and took over as CEO)
• Judith Campisi was there until she passed away 
• Henry Jasper was there, he’s now gone on to Genentech
• Gordon Lithgow and a bunch of other people working on aging
• It was a good group of people for sure

You alluded to something that happened in 2017, 2018 that brought a lot more interest into the field, what do you think led to this interest? 

• You just reach an inflection point, and it’s really hard to know what triggers it
• Calico started a few years before that
  • Google’s alphabet companies that was focused on longevity
• They’ve not been very open about what they’re doing, but it triggered a lot of publicity for longevity field
• It got Silicon Valley interested
• Brian and Matt used this slide that you have aging pointing to all these different diseases [shown below]

Figure 1. Diseases related to aging. Image credit: Brian Kennedy

Brian explains, “We started using that slide around 2005, and we were making the point around healthspan shortly afterwards and really this idea of preventing disease and keeping people healthy, interacting earlier.”

• Now Brian is so sick of that slide; he can’t look at it anymore
• Back then, there were a few scientists doing it and it finally helped trigger a movement (hopefully)

Do you think the field would’ve accelerated sooner had it not been for some notable setbacks? 

• For example, resveratrol
  • Peter doesn’t remember exactly when GSK bought resveratrol, around 2006, 2007
  • By about 2010, it was clear to him that was not going to work
  • GSK probably knew sooner

Do you think that that type of hype with nothing to show for it was a negative force in that equation and maybe this inflection point could have happened sooner,and it could have been easier 7 raised funds if there had been less of those examples? 

• It’s hard to know
• It’s unfortunate that investors made money off that deal when what was developed wasn’t going anywhere

It probably slowed things down a little bit because there’s always this doubt about whether you can slow the aging process  

• When you have a major effort that’s triggered around trying to do that, even though they ended up focusing on disease, and when something like that fails, it probably does slow down other investor interests
  • We can talk about the struggles of longevity biotech companies in that way

Today you’re in Singapore; tell me what you’re doing there  

• Brian has one foot in academics and one foot in the private sector these days
• On the academic side, he’s really focused on targeting aging
• And that comes back to what he alluded to with the biotech companies a minute ago: a lot of them are targeting aging pathways, but to raise money and get their drugs tested, they have to turn to some disease indication (which is understandable)
• The companies he’s involved with do that too, but that’s not what we really want to do

“What we really want to do is slow the aging process and keep you from getting sick.”‒ Brian Kennedy

• In an academic setting, we can test that clinically
  • We basically have a whole range of animal models, a pipeline from yeast, worms, flies, killifish, mice, and humans (billion years of evolution there)
• We bring interventions in at the right place, validate them, really believing the idea that if it works across different model organisms, it’s more likely to work in humans
• Then we design human clinical intervention studies to validate that they’re targeting the aging process

Brian adds, “I don’t think anybody knows exactly how to do that yet (including us), but we’re doing our best and learning as we go.”

How is the institute you’re at funded? 

• [Brian is at the Centre for Healthy Longevity at National University in Singapore]
• Mostly through the university and the government in Singapore, but we also have some philanthropy, and we do contract sponsored research to test interventions from companies sometimes

How many PIs are there? 

• Brian runs a program that has about 35 PIs in it
• But a lot of them are doing other things
  • They’re not all focused on that one concept he just spoke about
  • They have their projects around Alzheimer’s disease 
  • Or we just have this guy Michael Chee, who’s working on sleep and aging, which is so understudied
  • It’s kind of like an academic department where people have their own projects they’re focusing on

Is there any department at a US university that brings together as many people that are focused on specifics of aging this way?

• Brian doesn’t think so, although it depends on how you define aging
• If you branch it out to cancer then there are, but he’s not sure if that is focused on the actual aging process 

Rethinking the biology of aging: why models like the hallmarks of aging fall short [9:45]

• Peter wants to start with a question that he thinks they’ll end up coming back to because it’s so fundamental

Peter adds, “I enjoy going down the rabbit hole of fundamental questions in physics.”

What do we think is actually causing aging? 

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