The Cocktail Report (sound really smart around your friends):
An enzyme called AEP rises with age in the cells lining blood vessels, and it chops up NAMPT, the enzyme that controls how fast the body makes NAD.
Mice built to overproduce AEP in their blood vessels lived roughly 250 to 290 fewer days at the median than normal mice.
In fast-aging mice, NMN pushed median lifespan from 521 to 673 days in males, while an experimental AEP blocker reached 718.
Neither treatment reduced tumors or disease burden at death.
The blocker, CP#11A, has not been tested in people, and the lifespan gains came in a genetically sped-up model, not in normal aging.
If you take NMN or nicotinamide riboside, you are betting on a simple idea: NAD falls with age, so topping it up should help. A study published September 17 in Science Advances suggests part of the problem sits upstream, in the walls of your blood vessels, where supplements may not reach.
NAD, short for nicotinamide adenine dinucleotide, is a molecule every cell uses to turn food into energy and to run repair enzymes. Levels drop with age, and the reasons have never been fully clear.
A vessel problem first
A team in Shenzhen, China, looked at endothelial cells, the thin layer lining every blood vessel. In a small set of human muscle and brain samples, and in mice, older samples had fewer of these cells and more of two proteins called C/EBPβ and AEP.
C/EBPβ is a switch that turns genes on during inflammation, and one gene it switches on makes AEP, a protein-cutting enzyme. The researchers found AEP slices NAMPT, the enzyme that sets the pace of NAD production, at one specific spot.
With NAMPT cut, NAD fell and the vessel-lining cells showed signs of senescence, the state in which cells stop dividing and release inflammatory signals.
What happened to the mice
The team bred mice that overproduced AEP only in their vessel linings. Median lifespan dropped from 769 to 518 days in males and from 807 to 520 days in females.
These mice had weaker blood flow responses, leakier blood-brain barriers, less running endurance, and worse memory. A second strain that overproduced C/EBPβ in the same cells showed similar problems.
Blocking the cut reversed much of the damage. Fast-aging mice given a version of NAMPT that AEP cannot slice kept more NAD and lived longer, and in normal 20-month-old mice, turning down AEP only in blood vessels improved strength, endurance, and memory.
NMN versus the blocker
Here is the part that bears on your supplement shelf. Starting at 10 months of age, the fast-aging C/EBPβ mice ate plain food, NMN, or CP#11A, an experimental pill that blocks AEP.
In males, median lifespan was 521 days on plain food, 673 days on NMN, and 718 days on CP#11A. In females, it was 530, 668, and 723 days.
Both treatments raised NAD in muscle and brain, with the blocker raising it more. CP#11A also restored blood vessel density and blood flow responses, and blood and urine tests showed no liver or kidney harm.
Reasons for caution
The lifespan gains came in mice engineered to overproduce a protein from birth, which the authors concede does not mimic how these levels creep up in human aging. In normal old mice, the team measured function, not lifespan.
Many lab measurements used only three animals per group. Neither NMN nor CP#11A lowered tumors or overall disease at death, so treated mice lived longer with the same illnesses.
The authors declare no competing interests. CP#11A comes from the same research group's earlier work and has not entered human trials.
What this means for your NMN habit
If you already spend money on an NAD booster, this study neither vindicates nor sinks it. NMN helped these mice, and the authors cite human trials in which NAD boosters raise blood levels but deliver uneven benefits.
The study offers one reason why: if an enzyme keeps cutting the machinery that makes NAD, adding raw material only goes so far. That is a hypothesis to watch, not a reason to change what you take.
Why Should You Care?
Blood vessels may be where NAD decline starts, and fixing that upstream step worked better than NMN in mice. Until a blocker like CP#11A is tested in people, the practical move is to keep expectations for NAD supplements modest.
1. Li B, Nie S, Wang M, et al. Endothelial C/EBPβ/AEP pathway drives vascular deterioration and systemic aging. Science Advances. 2026;12(38):eaed1961. doi:10.1126/sciadv.aed1961. https://pmc.ncbi.nlm.nih.gov/articles/PMC13580549
