Plenty of other options if you want extensive coverage of biotech deals. If you want to chuckle your way through a masterful Lovecraftian exposition of JPM, look here.

Healthcare has to change

Many discussion threads felt like loose ends of a fraying fabric: US healthcare can’t continue in its current form. With luck, this will help enable longevity medicines.

People are frustrated by costs and a lack of agency in their own (proactive) health. Biotech companies and investors too are frustrated by the cost of bringing drugs to people, driven in part by the cost of US-based clinical trials. Every part of healthcare is getting more expensive, faster than the medicines we usually complain about. While HHS enthusiastically champions FDA modernization to address these issues, consumers are increasingly exploring ways to sidestep the agency entirely.

Healthcare won’t change overnight, but some things will shift in the next few years.

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The DIY Health Zeitgeist

• Everyone wants GLP-1s. After a brief gold rush for aggressive telemedicine companies, Novo and Lilly obliged by launching direct-to-consumer sales. Once that door was opened and subcutaneous injections become normal, people start asking what else is available. This triggered a big ‘Chinese peptide’ craze, including various experimental drugs still in clinical trials. The ‘peptide’ brand is so strong that some pill mills are labeling non-peptide drugs as peptides…

• The FDA should recognize the latent demand for agency on our health, and adapt accordingly. As it is, the peptide craze has ushered in a wave of longevitainment, normalizing circumvention of a ‘too reactive’ healthcare system in favor of a pre-FDA 'apothecary' model informed by friends and tweets. Much like the apothecaries of old, most consumers won’t benefit, and some will be harmed. For complex diseases, the FDA plays a critical role in enforcing scientific truth-seeking. If medicine ends up like supplements, either from too aggressive deregulation or from lack of adaption leading to consumer actions, we’ll stop getting medicines that actually work because sales costs less than science.

N=1, or ‘DIY with a vengeance’

• Some who want greater medical agency have urgent, life-or-death, reasons1. Some cancers and genetic diseases are so rare that treatments are effectively personalized to a single individual, which our healthcare system isn’t set up for. and organized a great event to discuss what would help expand options for patients who need such therapies.

• Notably, the FDA announced a new ‘Plausible Mechanism’ pathway (which you’d think they would have published open access…) last year. Former commissioner Janet Woodcock published a response bringing in ideas from how we treat surgery, which notably does not need clinical trials before doctors can try new ideas. It’s interesting to think about how doctors could be enabled to try new treatments and combinations in order to support preventative medicine broadly.

• Stepping back, the N=1 model could be a powerful way to accelerate medicines when the readouts are clear, like weight loss, cancer, or viral load. But for prevention and any disease without black-and-white outcomes, scattered N=1 trials won’t give us any clear answers. The solution is to establish thoroughly validated surrogate endpoints, like cholesterol, to give us clean data across small trials.

The Geopolitics of Clinical Trial Abundance

• and coined the excellent term ‘Clinical Trial Abundance’, and hosted an event on this topic. This is largely in response to the rising trend of US biotech running trials overseas where costs can be halved and investigator-led trials can be started months than in the US. Or, of course, rely on China to run faster trials and buy assets with human data. You can imagine that this is not a desirable state of affairs for the FDA/US government.

• Longevity companies are hit harder than most, even if they don’t run actual aging trials, given the costs and durations for age-related diseases. The Alliance for Longevity Initiatives (A4LI) hosted an event where Jim' O’Neill and longevity biotech leaders discussed options for cheaper and faster early human data in the US. A common concept here is a ‘barbell strategy’, where we make sure early trials are robust on safety, then grant accelerated approval based on reasonable evidence, followed by rigorous enforcement of confirmatory evidence. This would move longevity trials out of ‘untenable’ territory by enabling commercial returns within the drug patent life. Notably this mechanism already exists in veterinary medicine (which Loyal is taking advantage of).

These are aspects of the same broader trend: As healthcare costs rise it becomes more expensive to prove that drugs work in humans which kneecaps new drugs and preventative medicine, the rare parts of the healthcare system with the potential to improve care per dollar. This trend has been ongoing for a long time, and consumers increasingly want to take health into their own hands. Something has to shift.

Solutions & progress

ARPA-H National Longevity Strategy Roundtable

• organized a roundtable, where a group of academic and biotech leaders came together with ARPA-H leadership to discuss bottlenecks for longevity, and where ARPA-style projects could push us past the ‘valley of death’ between academic work and market-driven progress.

• Key takeaway is that ARPA-H is keen to do what it was made to do: Take bold bets that could fundamentally change how we keep Americans healthy, and is looking seriously at longevity science for ways to do that. This is great! I’m hopeful for followup to produce impactful new ARPA-H programs.

• There was also discussion of how to incentivize medicines that prevent age-related diseases. This kind of medicine simply isn’t financially viable without some kind of accelerated approval pathway, because the time to make the medicine and show effects in humans would eat up almost all of the 20 year patent life. Surrogate endpoints is one way out of this conundrum.

• One of the most important thing ARPA-H can do for longevity is to create a ‘CASP for measuring aging’ to address the surrogate question, as I wrote about earlier this month:

Pharma keeps tip-toeing in

• This year’s JPM had at least two sessions organized by investment bankers, and I kept seeing longevity companies and investors in the floor Eli Lilly had rented. Other pharmas also made comments about curiosity around longevity (typically alongside questions about endpoints and accelerated approval).

• One topic discussed both at the roundtable and elsewhere is how best to make use of the trove of ‘non-commercial’ drugs that the biopharma industry has created. Drugs whose patent life has expired, or that simply aren’t doing well commercially. This would be a cool way for pharma to dip their toes into longevity trials, without adding risk to the blockbuster drugs that keep them in business.

• Clearly defined trial requirements, with accelerated approval, is likely needed to unlock more companies investing in longevity. There are many ways the HHS could act on this, ranging from new regulatory mechanisms to simply issuing crystal clear guidance documents for diseases of aging.

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6 months ago · 166 likes · 23 comments · Elliot Hershberg

The above is AI slop (from a real LinkedIn post). You probably noticed writing patterns: the contrasting antithesis, the staccato rhythm, the redemption reveal. But the crime of slop is posting content with zero thought behind it, not using tools to make text or images.

Certainly no thoughtful curator was involved in recommending you avoid drinking water for seven days1. The Shloppoth does not seek to understand what it posts, merely to shape words into the most view-optimized form by hijacking our curiosity and tendency to trust ‘explainers’. It is the triumph of volume over value, content with a polished appearance concealing an gaping void. The output of an inhuman abomination ingesting news and press releases and turning them into engagement.

People have written about the dead internet and brain-rot perils of slop content (and sometimes in pseudo-defense of it). But we are here to warn you about another peril. For the Shloppoth and its marketer acolytes are not content to post about work-life balance and investment advice. They are ever seeking fertile topics to devour, and this year have come upon the sapling forest known as “longevity”.

That’s right, gentle reader. Just as our field has begun to generate solid data that aging and its mechanisms can be targeted to prevent disease and extend lifespan, the channels for learning about its progress are getting jammed by low-quality content: evergreen fitness advice becomes ‘optimizing longevity’, spas add a few (untested) supplements to become ‘longevity clinics’, and Shloppoths furiously expand already-exaggerated news headlines into bullet lists of ‘proven longevity benefits’.

The worst of this is truly “longevislop”: high-volume, ungrounded, and unhelpful. It tries to adopt the aesthetics of science without even a modicum of its rigor and truth-seeking. It speaks with absolute confidence, promising “reversals” and “resets”. Combined with the soothing words of wellness influencers and the ads of supplement vendors, longevity is becoming more of a vibe than a biomedical discipline.

Some serious longevity scientists are brandishing the term ‘geroscience’ to distinguish the productive meaning. It’s a perfectly suitable term, if a bit passive. But it’s also clunky enough that we doubt anyone not wearing a suit or a lab coat will adopt it.

Instead, offers the discerning reader a guide to dissecting content branded as ‘longevity’, to understand the nutritional value of different varieties.

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Axis 1: Is it even longevity?

When you come across “longevity news”, first ask yourself whether this information already exists under a different name? If your grandmother got the same advice from her doctor decades ago, it’s probably not longevity science. Sure, anything that affects your health technically affects longevity, but we don’t need a new term for that. Longevity science as a discipline worth paying attention to delivers new insights and ways to increase longevity.

This gives us the first axis for separating out content: Is it even longevity?

On the right end of the spectrum, you have scientific progress that wouldn’t exist without the longevity field: new science, new therapies, and new understanding of aging itself. You still need to determine whether it’s good science (we’ll get to that), understand whether it’s early stages or ready for human trials, and more. But it’s at least in the class of content that could lead to many more years of health.

In the middle, you have things like GLP-1s or drugs focused on individual diseases. These represent real scientific progress and can have big impacts on diseases of aging, but they’re not uniquely “longevity”. They would have emerged from the fields of metabolism or neurology even if nobody was thinking about aging biology.

And at the left end you have rebranded wellness. Sleep well, exercise, don’t smoke, eat vegetables. All true, all useful, but nothing new. People knew it a year ago, ten years ago, a hundred years ago. It exists independently of any longevity research. Follow it perfectly and you’re optimizing for a healthy 78, not a possible 120. There’s nothing wrong with that, but it’s not what the longevity field is actually trying to do.

Axis 2: Who’s your source?

The second question to ask is whether the source is both capable of and interested in finding and communicating the truth. Noise on the topic of longevity is still noise.

On one end, you have informed sources who think deeply about their topic. These are people who have done the work to digest news and progress, who understand context and relevant events from the past, and who are clear about what do and don’t know. They are genuinely truth-seeking, and bringing you along for the ride. If you asked them a harder question, they could answer it thoughtfully. Following people like this is an amazing way to learn, because they compress hours and years of learning into useful updates on the world. Let’s give them an award:

In the middle, you get people who are excited about what’s happening. They’re likely to take new findings at face value, lacking the time and/or expertise to evaluate. They sometimes like to fit data to commonly held beliefs, and other times are wildly overoptimistic. Compared to the award-winning burger above, consider them a random restaurant with a ‘World Famous’ sign in the window: You will most likely not get what you’re being promised, but it’ll be a burger. Maybe it’ll be awful, maybe it’ll be delicious. No guarantees can be expected from this kind of source.

But there’s a type of source that’s worse than the uninformed/unrealistic: The Slop. The over-hyped burger is at least a burger. Someone tried to give you information, maybe they didn’t do the best vetting but at least you can digest it yourself. Slop has no information: it is headlines run through LLMs, with no thought or craft behind it. It cycles through topics (peptides, fasting, telomeres, epigenetics…) with no context or memory, without relating observations to each other. In the world of would-be burgers, slop is raw ground beef:

Don’t eat it. It could be actively dangerous, and it certainly won’t make you better off.

The Longevity Slop Map

When we put the two axes together, we get a map:

In the bottom-right (legit but not longevity) is what we might call longevitainment. For those who genuinely want longevity, this should be considered entertainment with a longevity aesthetic: activities, purchases, and engagement that makes you feel like you’ll live longer, but that won’t actually make a big difference to your lifespan. Think cold plunges, saunas, red light, and sleep scores. Honest claims of minor health effects, possibly with nice brand. You’ll feel good, stay fit, probably be healthier and at least won’t get hurt. That’s great, as long as you know what you’re getting.

Moving left we get to a wellness hype zone full of sales pitches. ‘Forget going for a run, this new type of exercise will give you unheard of results’ or ‘This faraway group of humans have health secrets you’ve never heard of’. If you believe these claims you’re likely to be disappointed, although you might have a good time. Unless, as typically happens, you were asked to put down a credit card before partaking.

If we move up to uncritical longevity, we get a mix of people who are sure that indefinite lifespans are around the corner, or that the FDA is the only thing standing in your way. Clickbait journalism lives here, giving a false impression of progress. The innocuous enthusiast version is perhaps not very constructive, but at least sincere and well-intentioned. The edgier version wants you to fly to Honduras to inject gene therapies - most likely will do more harm than good given how few medicines made by professionals end up working, but not impossible that something will work. All we’ll say here is that this quadrant has been around for a long time, and we’ve yet to see a breakthrough come from there.

Left of these two hype zones is the terrifying realm of longevislop. This is almost certain to be a grift, either for your money or your attention. Just say no.

Norn Group’s recommendation is a diet primarily consisting of the top right quadrant. Listen to truth-seekers who put lots of effort into understanding the world, explain the science of why we age and probably don’t have to. Celebrate when they get excited about a breakthrough, and pay attention to what they spend time talking about.

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A Field Guide

For readers interested in understanding real progress in longevity (for example towards Norn Group’s mission of enabling a sixty year-old to liver another sixty healthy years) we suggest the following checklist for your precious attention:

First, ask whether the same content exists without the longevity field. If so, is there a unique angle/update? If you’re just being told “sleep and exercise”, you’re on the lower part of the quadrant and should adjust your expectations accordingly.

Second, ask whether this person has done the work to understand what they’re saying. Polish people can pay for, depth not so much. A history of engaging in discussions and tackling hard questions with humility is a good sign. A background in aging science (rather than say marketing) ditto. If big news came from an iffy source, look for a more credible source treating the same topic.

Third, check for financial conflicts of interest. Anyone who is trying to sell you something is automatically less credible. Not necessarily wrong, but look for neutral third-party evaluation. Also ask whether it would be oh so lovely to believe something is true. We all want medical breakthroughs, so pitching them is easy. For anecdotes like “I reversed my age by 12 years”, it’s best to ask ‘how could this claim be wrong’.

Finally, when something is exciting and seems to come from a good source, ask yourself ‘what would normally happen next’, and check back on that later. Drugs with great effects in animals tend to move to human trials, research breakthroughs are picked up by other labs.

The longevity field is growing, but a lot of apparent growth is noise. Follow the data.

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Science Highlights (skipping most of the published work)

They had parallel tracks this year, so I didn’t catch every presentation.

• Max Yun shared details on aging in axolotls in her colony. They live ~10 years and regenerate throughout life. Many features of human aging are absent: 1) no senescent cells, at least by common markers, 2) no telomere shortening, 3) no loss of stem cells, 4) their thymus doesn’t disappear like in humans, 5) ~flat risk of death by age. So how do they die? She doesn’t know yet. One observation is that their adaptive immunity is very weak, leaving them prone to infections (this is also true of naked mole rats).

• Apropos, Emma Teeling shared findings from large-scale epidemiology and sequencing of different bat species finds that short-lived bats have increased innate immune activity with age, while long-lived bats decrease activity.

• Björn Schumacher and Zane Koch showed early data linking the DREAM protein complex, DNA damage and repair, and neurodegeneration. This is cool both because DREAM is probably druggable, which DNA repair generally isn’t. And because while DNA mutations correlate inversely with lifespan, we don’t know what mechanisms are involved. (Björn’s paper)

• Juan Carlos Belmonte of Altos and James Kirkland of Cedars-Sinai were both using transplant organs as a system for testing putative aging therapies - this is cool since it’s a real aged system, ‘transplant success’ is a fast readout, and success could have a commercial outlet before direct human application.

• More clocks, although still nothing with blinded prospective validation… Andreas Berger is looking to make single-cell transcriptomic signatures of cellular injury to compare with aging, by comparing overlaps between different injuries. Alexander Tyshkovskiy from Gladyshev lab made a cross-species, cross-cell-type transcriptomic clock that captures both in vivo and culture “aging” - to me, this suggests it’s focused on cell intrinsic changes, maybe epigenetic, since that’s what would be shared with cultured cells. Tony Wyss-Coray shared a (published) Alzheimer’s predictors based on YWHAG/NPTX2 protein ratio in CSF or blood.

• There was a refreshing number of presentations from labs new/adjacent to the aging field: Sophia Liu shared spatial transcriptomics exploration of thymic function and changes with age, Uri Alon is working on modeling species lifespan, and argued that heritability of lifespan is actually ~50% when you normalize for extrinsic mortality in twin studies. Very satisfying to see many of these funded by Impetus Grants a couple of years ago, now bearing fruit. Vadim Gladyshev/Bohan Zhang spoke about experiments to study accelerated/reversed aging when organs were transplanted between donors of different ages.

• Nice panels on virtual cells & pharma perspectives.

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New developments

• Todd White announced the non-profit Thalion Institute, intending to spend several hundred million on research and tools with an emphasis on comparative biology. One major component will be a biobank of samples from species with long lifespan or exceptional disease resistance, through life. Assuming this all happens, it should be a great source of new therapeutic hypotheses.

• Attendance by pharma companies was higher than ever. Eli Lilly had the greatest presence, consistent with their investment in a new longevity-focused group. During a talk they described GLP1s as “the first longevity drugs” based on their broad effects, as did Lotte Bjerre Knudsen of Novo Nordisk. Novartis and Genentech agreed with this description on a panel. AstraZeneca and Lundbeck were also present. Not all of these are investing in longevity, but all were paying attention and looking for opportunities.

• There was a lot of discussion of longevity medicine, and three clinical trials stand out for potential to shift status quo: 1) Eli Lilly’s Alzheimer’s Primary Prevention rial was mentioned (no data yet), which is a rare example of treating for prevention. These trials are expensive but have potential to unlock new surrogate endpoints to speed up later trials. 2) FAST, not strictly a trial but rather using samples from past trials of putative longevity drugs to identify biomarkers of aging. Impetus gave a small amount of early funding, which has now been expanded by Astera and others. No data yet, but excited to see results. 3) Another Impetus-funded trial is VIBRANT-I, testing rapamycin to delay ovarian decline. Youin Suh says they’ll be able to unblind and analyze data by the end of the year. VIBRANT-I one is particularly exciting because the design could be a platform to test other candidate longevity therapies much faster than multimorbidity/morality trials (plus delaying menopause is by itself a huge need). A larger VIBRANT-II study is already bring planned. If this works out it could majorly speed up and validate the field.

Congratulations to organizers Morten Scheibye-Knudsen and Alex Zhavoronkov for a great event. Looking forward to next year.

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