Fight Aging!

I was recently in London for the Longevity Week, a collection of single day and evening events organized by investor Jim Mellon of Juvenescence and supporting groups. Varied events focused separately on (a) educating investors in the science of aging, (b) generating a larger investment community for the new longevity industry, and (c) improving the non-profit world and its efforts to explain the merits of treating aging to the public, to bring therapies to the clinic, and to improve the state of older life using presently available tools. Jim Mellon clearly understands that building an industry focused on the medical control of aging, particularly in regions where medical development and clinical practice is so very heavily regulated, requires raising the water level when it comes to understanding of that industry and its potential.

The first event, the Science Summit, was a small and selective gathering that I was kindly invited to. It was the successor to an earlier master class on the science of aging organized for an audience of investors interested in the field, based on the concept that investors, and then the field as a whole, will benefit from a better understanding of the underlying science. I should say that these are largely investors in funds rather than investors in companies, occupying the higher valuation end of the investment community. These are people who, collectively as a class, have a lot of influence over the shape and pace of development of future industries through their choices in what to invest in.

A number of scientists gave presentations on the field, eclectic in topic. Work on bisphosphonates was mentioned early in the day. You might recall that these were shown at the start of the decade to extend life span by five years in one cohort, and in numerous other studies have been shown to reduce mortality, heart attack incidence, and so forth. This was one of the early examples that prompted the question of whether or not it is reasonable to expect there to be any sizable effects on life span hiding in the existing portfolio of medical therapies, unnoticed. This was, of course, well before the advent of senolytics to clear senescent cells, and the discovery that numerous existing drugs and supplements may be senolytic to a degree that will affect life expectancy in patient populations. When it comes to bisphosphonates, it has been challenging for the research community to raise funds to study the mechanisms involved, so little work is ongoing on the possible mechanisms. This is a common theme in scientific research on interventions in aging, sad to say. Effects on life span due to bisphosphonates are thought to depend on improved DNA repair and reduced levels of cellular senescence, but this is far from confirmed, and these drugs do have non-trivial side-effects. The likely future course of development would involve the slow process of identifying the important mechanism and then finding alternative ways of targeting it.

There was a fascinating presentation on the use of 670nm wavelength light, showing that in a number of different species it can improve mitochondrial function in the cells that the light reaches. In small animals this wavelength can penetrate much of the body and brain. The underlying mechanism by which mitochondrial function is improved in cells under this wavelength of light is unclear, but it would be interesting to see researchers comparing the effects of this with, say, NAD+ upregulation, in search of a better understanding of the general malaise that affects mitochondria with aging. Which parts of the problem are the most important? Given quite distinct forms of intervention - light and small molecules - one might have a chance of learning by comparison.

Another interesting point that emerged, watching presentations on a variety of topics related to the biology of aging, specific age-related diseases, and programs of development, is that cellular senescence now appears near everywhere. Scientific programs that wouldn't have mentioned cellular senescence as recently as five years ago are now fitting it into their work, or making it a focus. We might treat this as a leading indicator of what the senolytics industry will look like a few years from now - there will be many, many companies and development programs.

The final presentation of the day was by Joao de Magelhaes, and he spent some time discussing the question of how development of therapies for aging might fail. The point of thinking about this is of course to prevent this from happening - to convince ourselves that either matters are progressing well, or that there is something important that must be done in order to enable matters to progress well. Do we actually understand how and why aging happens? Are animal models too different from humans in ways that matter? While stress responses related to calorie restriction appear very similar across most species examined to date, and these processes influence life span, is that really representative of the degree to which processes of aging are different between species? Can the results of any human trial of at most a few years really tell us anything about what a therapy is doing to aging over the long term of decades? Are we successfully prioritizing and selecting which of the limited number of research projects and trials can be conducted, given the resources to hand?

The second event, Investing in the Age of Longevity, was a part of the investor-focused programs organized by Jim Mellon's Master Investor organization, a way to promote understanding of - and participation in - the longevity industry among the members of the broader investor community. This is of course of great benefit to Juvenescence, cofounded by Jim Mellon, but it is also of great benefit to everyone else. If we are to see this industry thrive and deliver on the promise of treating aging as a medical condition, it absolutely must be promoted and made interesting to the investment community. The day opened with an overview of the state of science to slow or reverse aging, and examples of specific programs, by Aubrey de Grey, Nir Barzilai, and Michael West of AgeX Therapeutics. Their overriding theme was that things have changed since a decade or two ago, that we've reached a tipping point, that now is the time to really work on bringing therapies to the clinic. The scientific and technical capabilities, the arrival of capital, the changing of opinions, all have advanced considerably since the turn of the century, and things are changing ever more rapidly year to year now. Then investors, including Laura Deming of the Longevity Fund said much the same thing from their perspective on the space.

The afternoon saw the showcasing of various companies, biotech startups working on aging in some way, and at different stages of progress. I presented on Repair Biotechnologies, alongside a number of other founders. In our own way, the startup entrepreneurs of the field also demonstrate that now is the time, that things are moving rapidly - if it wasn't, if they weren't, then we wouldn't have each recently chosen to start a company in the space.

The final event was the yearly Longevity Forum, in which the focus is on non-profits, governments, and the process of explaining the promise of treating aging as a medical condition to society at large. While it is quite possible for a small group of people, a small research and investor community, to build the first rejuvenation biotechnologies that will change the world, it remains the case that, on the large scale and over the long term, public support is vital to generating an industry and bringing rejuvenation therapies to the world. We want a world in which the average fellow in the street thinks of aging in the same way as he thinks about cancer: that something should be done about it, and that it is obviously a good idea to fund research into therapies that can treat the condition. This change won't happen by itself. It requires a great deal of work on the part of patient advocates and others, and hence the need for conferences and other community gatherings.

The Longevity Forum started, as on the previous day, with researchers talking about the state of the science, and why this is an exciting time - just to a different audience. From there it moved to discussions relating to the involvement of government and non-profits in the process of deploying means of slowing or reversing aging, and then moved back and forth between the science on one hand and the interactions between government, public, and public health services on the other. The UK has set the goal of extending healthy life span by five years by 2030, and this had a central place in the presentations of the day. It was an interesting mix of (a) those people who want to address aging in only a very minor way, via better diet, exercise, and ordinary preventative healthcare, and who think it will be a struggle to make progress, and (b) those people who are looking at the development of therapies to produce more radical changes in life span. Watching these two factions interact is quite interesting. It is a microcosm of what will happen over the next few years as people start to realize that senolytics will have a major impact on the state of human aging. What will happen to the community of people fixated on diet, exercise, and improving NHS and local health authority practices when it becomes clear that cheap senolytics produce a meaningful degree of rejuvenation?

Alongside the three days of events were evening gatherings of folk in the longevity community, a chance to catch up with people who are working on interesting projects, or funding those interesting projects. Much of the more important networking happens outside the events, as is ever the case. It was an interesting week, all told, and it is clear that we're all going to be very much better off in the years ahead as a result of the efforts of Jim Mellon and his allies and staff. This is a step up in the scale of advocacy for the treatment of aging in comparison to past years.