Longevity's "snake oil" problem.
What's gold, what's grift, and what are legitimate open scientific questions.
Longevity science has come into mainstream consciousness in the last 10-15 years with the funding of Google’s moonshot longevity company, Calico, and more recently with the Jeff Bezos funded, Altos Labs. And for good reason— the promise of extended years of healthy life in our generation is real, tangible, and I think even, inevitable. We should be funding these efforts heavily as they will have the biggest impact on human health since antibiotics and vaccines.
However, there is a long standing (ancient) problem in longevity, people trying to make a buck off of claims of “magical elixirs” and many of those are potentially very dangerous. Recently a reporter asked me “how do we know what’s real or not?”. This is a very good question and a specific instance of the more general question— how do we know that anything is real in science as a consumer? We have seen this during the pandemic from masks to vaccines to medications- figuring out what is truth, what is grift, and what is legitimately an unknown that we need more evidence to understand fully has been hard to sort through for most people.
I figure this out for scientific questions in my field by looking at and analyzing data myself, reading the extremely dense and specialized scientific literature, going to conferences where the science is debated publicly by experts, and speaking with other scientists. If science is not your full time job, then this method may be a little too intense and time consuming. We need better messengers who can explain information in a trustworthy and bite sized fashion. Unfortunately some of the loudest voices in longevity today are not always spreading reliable information. Below are some of my high level thoughts on what to trust and be excited about and what to stay away from in longevity. Approaches with a * appear in multiple categories.
GOLD
So let me start off with what I think are the most promising avenues in longevity:
Targeting aging pathways therapeutically to treat multiple age-related diseases.
a. Biologics and small molecules that have lifespan extending properties in animals that initially gain approval for one disease indication and then expand to other disease indications with the goal of extending overall healthspan/lifespan (BioAge Labs, Calico)
b. Partial reprogramming (Altos Labs)Gamifying and tracking lifestyle interventions known to extend life and healthspan— exercise, sleep, lower life stress, social connectedness, blue zone diets.
Improving societal factors that cause early mortality and poor health— access to healthcare, healthy food, clean water, clean air, and education, improving maternal mortality rates, addressing structural inequality, eliminating genocide, etc.
Adding youthful blood factors or removing harmful age-related blood factors*
Removal of pathological cells*
Organ replacement— organ transplants will continue to improve and extend life and healthspan.
Brain Computer Interface- think operating artificial limbs with brain chips.
GRIFT
Here are what I think are the most dangerous and deceitful longevity plays happening:
Unregulated gene therapy for Telomerase, Follistatin, Klotho or similar happening in places with regulatory loop holes, like Honduras. These have no evidence for working, don’t make sense from a scientific perspective, and likely will kill someone by inducing cancer or liver failure. People should ask themselves why these companies are not going through traditional regulatory pathways if they have technology that they believe actually works and is safe (ie. why miss out on a $100B opportunity?).
Unproven and unregulated sale of supplements that have little or no human safety or efficacy data. Many of these companies make unsupported claims of lifespan/healthspan benefits and have no plans to conduct clinical trials to back up those claims. >30,000 people/year in the US go to the emergency room for supplement-related toxicity. Since the composition of these compounds is unregulated, anything could be in them.
Diagnostic companies that are telling consumers that they are low in something (NAD, testosterone, etc.) when they are in the normal range in order to sell them a supplement or intervention.
UNCLEAR EVIDENCE
Here is what you may see scientists debating on social media with more evidence needed to determine the success of these strategies
Removal of pathological cells* there is a lack of scientific consensus with some approaches. It should be noted that there are dozens of companies in this category with many different approaches, each of which should be considered independently. There have been successful clinical trials but there are also still question marks in many cases.
Adding youthful blood factors or removing harmful age-related blood factors* There is a lack of a consensus with some approaches and also some successful established companies. Each company (of which there are many) should be evaluated independently.
FDA approved (for a disease) compounds that extend lifespan in some animal studies— rapamycin (organ transplant, cancer), metformin (diabetes). Some of these compounds extend lifespan in mice or other animals to varying degrees and with varying consistency across species, sex, and lab conditions. These may or may not be safe or have tolerable side effects in contexts outside of the diseases they are approved for. I have some safety concerns with metformin for non-diabetics. Some scientists are pushing for aging to be recognized as a disease indication so that clinical trials can be run to test these compounds for healthspan and lifespan extension.
Supplements with mixed evidence for healthspan/lifespan improvement in animals that appear to be safe in humans— NAD, resveratrol. These compounds extend lifespan in mice or other animals to varying degrees and with varying consistency across species, sex, and lab conditions. Clinical trial evidence is insufficient in humans but generally shows modest or no benefit depending on the indication, and very few side effects or safety concerns. Overreaching claims are being made in selling directly to consumers in some instances (ie. stating that a clinical trial was positive when it was negative) that venture into the “grift” category.
IT WOULD BE GREAT IF IT WORKED, BUT THERE IS LITTLE OR NO EVIDENCE THAT IT WILL WORK YET IN HUMANS
Neuronal replacement There is some animal evidence that injecting stem cell derived neurons into the brain can replace neurons that have died. There are some technical challenges with neuronal wiring and survival of injected neurons. There have been no successful neuron replacement clinical trials to date.
Cryopreservation— freezing people or animals with the intention of “waking them up” later. This has been going on for a long time and recently has come back into popularity. We so far have not been able to “wake up” any animals more complicated than worms.
SCIENTIFIC DEBATES/CONTROVERSIES
Whether certain genes are actually “longevity genes”- Sirtuins, AMPK, FOXO, PI3K, Klotho, etc.
What biological aging actually is and how we should define it.
What biological aging clocks measure in terms of functional outcomes, disease, and lifespan and whether they should be called aging clocks.
THE BOTTOM LINE
Longevity science has great potential for extending years of healthy life. Watch out for those skirting regulation, especially when it comes to gene therapies and supplements with no evidence to back them in humans. Companies that are following standard regulatory pathways have a lot of potential and have seen some early clinical success in extending healthspan. We should be excited!
You can follow me @DrGlorioso