Noted researcher Gordon Lithgow is here interviewed on the future of the aging research field. The focus is on academic funding, career, and whether or not current mainstream efforts to slow aging via alteration of the operation of metabolism in order to slow damage are the right way to go. It can be argued that the major problem in aging research is that there simply is next to no funding in comparison to other fields of medical research. The research is thus stuck moving slowly, at a point of great potential but with limited progress towards a coherent community of researchers all heading in what is definitively agreed to be the right direction for therapies to control aging. This is not because the field is currently divided and that there is much left to determine about cellular metabolism in aging, but because the funding isn't large enough to plow through these problems in a reasonable amount of time and thus quickly determine and prove which of the available options for development are actually the basis for viable human therapies.
It was odd that I ended up studying aging. I got into it not really knowing that, just seeing a profoundly mysterious process that there was no papers on, as far as I could tell. In the last 25 years, we've got textbooks on worm aging, we have signaling pathways and hormones and so, so much, it's great. But I still struggle to tell people what aging is. I tell them narratives about protein and protein insolubility during aging and how that could be driving dysfunction, but it's still hard to really say to someone, "This is what aging is". And now more than ever, beyond curiosity it's this idea that while it's been a great privilege to just be able to mess around and do science and find stuff out, actually what we've found out could be useful for people. It motivates the research somewhat, but also how I talk about the research, and my willingness to go off and do public stuff to try and turn people's heads to thinking about this. And it drives me crazy that we're training a group of scientists who are very comfortable with the biology of aging and the idea that it causes multiple diseases, who are very comfortable moving from discipline to discipline as you have to do in aging research, and unfortunately there's no jobs for these people.
Funding has been flat for 15 years in aging research. We're still here, the institute's growing. It wasn't for a while, but we're gonna be hiring again and creating some new jobs, so it's not like nothing's happening, but compared to what should be happening, and what the science is telling us we should be doing, it can be a little frustrating. We've seen our own people go to Calico and Unity Biotechnology, which is a spinout biotech from the Buck Institute that's doing very well. There have been many false dawns of aging companies and aging biotechnology going back 15 or more years, but with Calico and Unity it feels different. It feels like they're serious about finding cures to diseases based on aging technologies. And I hope they're going to be big employers.
The biggest obstacles right now is funding at every level. Translation. We've got a lot of information and compounds that we need to move forward. Obviously those two things are tightly related. Funding also is at the heart of the inability to grow the field with these new scientists. It's just so sad, people with fantastic skillsets leaving science or going into industry, and not in an aging context at all. I don't think that there's a problem with the science. In past years we could have said that there's a big problem because people don't understand the evolutionary origins of aging, or problems in the past where people were very dogmatic about it being down to one mechanism or another. And there was literally a time when many people in the field thought cellular senescence was an artefact of the culture dish and couldn't really be important in aging, because it didn't happen frequently enough in animals. And now we're at a point where we're thinking no, chances are it's really important. So a lot of the factions are melting away and you're seeing much more unity in this paradigm of what aging is.
One possibility is that most of the modifications that we've made or interventions that we've made are really just optimizing interventions. That they're not really affecting the underlying biology of aging. It's hard to draw a hard distinction between optimization and changing the underlying biology, but essentially all the models that we use, flies, yeast and worms, they all come from the same ecological niche. They all have laboratory drift and we use lab strains that aren't the same as wild strains, and during that process we may have been creating problems and shortening lifespan for years, and now all we're doing is fixing some of those laboratory-based problems. That's one view of a lot of what we've done. If that were true, it would be a bit of a crisis. It's certainly the case that we seem to be hitting some sort of upper limit with things. We don't see lifespan being extended in mice by two- or threefold, like we've seen in worms. Even in flies we haven't seen twofold life extension. It's possible that we're hitting limits in our ability to extend lifespan. I don't know.
Yet there is no biological upper limit on lifespan. We have clams living over 500 years, bristlecone pines that are living hundreds of years and things. In theory, we could all live to 122, because one human has done that. So in theory we can at least do that well, which is amazing in itself. In theory, there are mammals that live even longer than that, so we should be able to live longer than the oldest human. Clams have a circulatory system, there's a beating heart, so if there are hearts on earth that have been beating for 500 years, why not our hearts. I don't believe in biological limits, because even in human life expectancy, every time someone says there's an upper limit, someone breaks it. I don't believe in limits of that sort, but how much you have to change the human condition to attain greatly extended longevity, I don't think we know. The empirical observation so far is that it's harder to produce strong effects in more complex animals. It could be because it's just that the experiments in more complex animals are more expensive, so a tiny fraction of the experiments we've done in worms have been done in mice. It may be that we just haven't hit on it yet.