🧬 The breakthroughs keep on coming. Now it's human longevity.

Also: 5 (more) Quick Questions for R&D policy expert Matt Hourihan

In This Issue

The Essay: The breakthroughs keep on coming. Now it's human longevity.

5QQ: 5 (more) Quick Questions for R&D policy expert Matt Hourihan

Micro Reads: ChatGPT, CRISPR, military drones

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Quote of the Issue

“The economy is a complex adaptive system with many billions of factors and feedback loops everywhere. Everything that is known is already priced in. Everything new is surprise. Prediction is worthless. In fact worse than worthless, it creates unwarranted confidence.” - Marc Andreessen

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The Essay

🧬 The breakthroughs keep on coming. Now it's human longevity.

The four broad areas of technology that I tend to track are artificial intelligence, biology, energy, and space. (Maybe five if you want to separate robotics from AI.) In each of those areas, we’ve seen some incredible advances and achievements in recent months, including: NASA’s successful launch of the Artemis I lunar mission (Nov. 16, 2022); OpenAI’s successful launch of the Chat Generative Pre-trained Transformer, or ChatGPT chatbot (Nov. 30, 2022); and Lawrence Livermore National Laboratory’s successful generation of nuclear fusion that produced more energy than it took to start the reaction (Dec. 13, 2022).

Space? Check. AI/machine learning? Check. Energy? Check.

Biology? Well, it seems like we can tick another box. Maybe tick it twice. On Jan. 5, San Diego-based Rejuvenate Bio reported that it had used gene therapy to deliver Yamanaka factors — proteins that reprogram adult cells into pluripotent stem cells, which have the potential to develop into any type of cell in the body — into 124-week mice, modestly extending their lifespan. And on Jan. 16, the scientific journal Cell published a study that both explained a new model of how aging works — degradation in the organization and regulation of DNA — and suggested how aging might be reversed. This is pretty cool. From Science:

To test the theory in mammals, the team genetically engineered a mouse strain that, when given a particular drug, makes an enzyme that cuts their DNA at 20 sites in the genome, which are then faithfully repaired. Widespread changes in cells’ DNA methylation patterns and gene expression followed, consistent with [the theory of [lead author David Sinclair, professor of genetics in the Blavatnik Institute at Harvard Medical School and co-director of the Paul F. Glenn Center for Biology of Aging Research]. The mice ended up with an epigenetic signature more like that of older animals, and their health deteriorated. Within weeks, they lost hair and pigment; within months, they showed multiple signs of frailty and tissue aging.

To see whether the epigenetic degradation was reversible, the researchers injected some of these elderly seeming mice with AAVs carrying OSK genes, which Sinclair’s group recently reported could reverse loss of vision in aging rodents. Analyses of the mice’s muscles, kidneys, and retinas suggest the cocktail reversed some of the epigenetic changes induced by the DNA breaks. The findings point to a way to drive an animal’s age “forwards and backwards at will,” Sinclair says, and support the idea of epigenome-targeting treatments for aging in humans.

In an interview with the Harvard Gazette, Sinclair expanded on the potential impact of the research:

Over the last 20 years, there have been a number of molecules that have been found to retard the aging process, at least in animals, and potentially a couple of drugs that are in humans. That made me optimistic that somebody who might make it to 150 has already been born. In this paper, we’re showing it’s possible to reset the age of the body up to as much as 50 percent. And, when you can reverse aging and not just slow it down, then all bets are off. We now know you can reset the eye multiple times and restore vision in old mice — that was our Nature 2020 cover article. In this paper, we’re showing that we can reverse aging in other tissues as well, using the same technology. So, if you can reset the age of the body multiple times, I think it would be dangerous to set an upper limit.

How real is this? Might we be getting anti-aging shots within a decade, if not sooner? Since I’m not a biologist, geneticist, or expert in the expanding science of longevity, I can take at least a couple of next steps. First, I can check out what true experts in all those things are saying. And the rough consensus here seems to be that the results are intriguing, and if borne out in further research, could be a game-changer. Sounds a lot like what experts have been seeing about the fusion breakthrough.