In the first piece in this series I made the case that the future of longevity supplementation is combinatorial: several well-chosen ingredients, working on different parts of aging, taken together as one system. In the second, I told you about sitting at my parents’ kitchen table with a binder of 1995 All-Star cards and having a eureka moment about DoNotAge® being like putting the best available players on the field at the same time.
This one is about how that team was actually assembled.
Last month, I sat down with Alan Graves, who founded DoNotAge in 2019 and now serves as its clinical research advisor. He was the person who drove the development of the 15-in-1. What I wanted from him was not a product pitch. I wanted the thinking behind it, the “why” in the details: why this formula exists, why these doses, and why this specific list of ingredients?
How it started
As many of you will be quite aware, DoNotAge did not begin as a 15-ingredient drink. Alan started the organization after running into his own aging problems and then looking to the existing market and finding no good solutions. The published biology, he said, was real. What was being sold on the back of that biology often was not.
“We set out to do the opposite,” he told me. “Be a health research organization that formulates, and then only releases to the public what actually works in people.”
The first years were single compounds. NMN. Spermidine. Ca-AKG (my personal favourite!). SIRT6Activator. That phase was necessary. You cannot learn what a molecule does, or what dose actually matters, if you start by throwing fifteen of them in a blender. What DoNotAge consistently heard was that its members got healthier. And over time, a pattern also started to show up: people were not taking one thing at a time, they were taking ten to fifteen ingredients a day.
And from personal experience, let me tell you: almost nobody can stay consistent with that many individual supplements for years, no matter how many benefits they are experiencing. I had to build a dedicated spreadsheet to manage all of my longevity ingredient orders! Few people are that obsessive!
In the interview, Alan put the problem simply: Consistency is where the results come from. You cannot go to the gym once and become strong. The second problem was scientific. If almost nobody is taking a single ingredient in isolation, you can never properly test the actual protocols people are putting in their bodies.
These two things coming together form the origin of the daily sachet. One finished formula. Engineered, as he put it, from first principles. An attempt to cover all twelve hallmarks of aging at once. And because it is a single product, they can put the exact thing members take into a randomized, placebo-controlled trial. And, of course, it becomes exceptionally manageable with all the ingredients in one place (my obsessive spreadsheet tracking habits may yet become obsolete!)
How was DoNotAge® formulated? Turns out, they mapped it backwards
I asked him how they chose these fifteen ingredients, and their specific doses.
The starting point was not “what is popular this year” or “what I heard on the most recent Huberman podcast”. Instead, it was following the biology. Aging, as the research community now describes it, is a set of interacting hallmarks: NAD decline, mitochondrial deterioration, senescent cells, epigenetic drift, and the rest. Some ingredients touch more than one hallmark. None of them touch twelve.
So they worked backwards. For each hallmark, what is the best-evidence compound? What dose actually does the work? The list, he said, more or less builds itself after that.
NMN, paired one-to-one with TMG, for NAD and the methyl pools that need protecting when you raise NAD. SIRT6Activator and trans-resveratrol for the sirtuins that NAD is supposed to power. Quercetin for senescent cells, and also because it helps resveratrol get absorbed. Spermidine for autophagy. Nitralis for nitric oxide, which falls with age. Then the metabolic and structural layer: Ca-AKG, CoQ10, hyaluronic acid, the D3 / K2 / magnesium grouping that does not work properly in isolation.
He was blunt about dose. Under-dosing, in this industry, is common. A label can say “contains NMN,” put 250 mg in the serving, and then borrow every study ever done on NAD. The routine uses 1,000 mg of NMN. That is a serious dose, and it is why the early clinical trial data showed an average 76% rise in whole-blood NAD in a few weeks. SIRT6Activator sits at 1,600 mg because that is what the researchers they work with have been using, and because they already had years of member data on it. Resveratrol came down from the old “a gram a day” recommendation to 500 mg as the data and the conversations with the people who actually study it evolved.
The part of the interview I keep coming back to
Plenty of companies now say they have run a clinical trial. Alan has sat on the other side of those conversations. And what he shared with me, you might find quite surprising.
A contract research organization (the ones most supplement companies use to claim they have ‘clinical trial data’ behind their products), he said, often does not open with “what gap in the science are we trying to fill?” It opens with “what marketing claims do you want to make off the back of this trial?” Then the study gets designed to produce that claim.
That is not how DoNotAge.org does business. Work like this is what Alan now leads on a day-to-day basis in his research advisor role.
For example, in testing the results of the 15-in-1 on cellular NAD+ levels, they sent the finished sachets and a matched placebo to an independent lab and asked a simple question: how much does this raise NAD? The lab did not know which was which. The participants did not know which was which. DoNotAge.org did not control the outcome. “That’s how science should be,” Alan said. “Let’s see what actually happens. Not: we want this outcome, so let’s make it happen.”
They also ran a 60-day wellbeing study in healthy adults. That one is not a biomarker study, and Alan was careful to say so up front. Wellbeing scores in the treatment group roughly doubled. Fatigue dropped about 19%. More than 90% said they felt better or a lot better. Every person in the treatment group said they wanted to keep taking what they had been given. There were no gastrointestinal side effects, which matters when you are asking someone to take fifteen ingredients in a few minutes.
Those are early results. They are not the end of the story. The research work continues. That is at the heart of what DoNotAge does.
What they are doing next
The next layer is the impact of DoNotAge® on biological age. They have longer epigenetic trials underway, including work connected to Steve Horvath and the Clock Foundation. Full blood draws, large enough cohorts to mean something, and a timeline that may stretch from six months to twelve, with the option to keep going. The point, as Alan described it, is not a press release in a quarter. It is being able to look, years from now, at people who took the formula and people who did not.
That kind of work is expensive. It only happens, he said, because the organization is set up to put profit back into research rather than treat research as a marketing line item. They also refuse the usual manufacturing shortcuts like the fillers that make capsules cheaper and faster to produce because he would not take those himself (and nor would I).
I asked him, near the end, what he wanted people to understand about why this formula is different.
He did not reach for a slogan. He came back to the same two problems he started with. People cannot stay consistent with a cupboard full of bottles. And until you put the finished combination into a proper trial, you are guessing about the thing they are actually taking.
The 15-in-1 DoNotAge® routine is their attempt to solve both.
If you have been following this series, you already have the argument for a multi-ingredient approach, and you have the picture of what it feels like when the best available pieces are finally on the field together. This is the part I wanted you to hear in Alan’s own terms: how the lineup was chosen, why the doses look the way they do, and what it means that they tested the product members actually drink.
The research is not finished. That is the honest version. It is also the reason the formula exists in this form at all.
Nick Engerer
Strategic Advisor, DoNotAge
