Research in mice suggests that excess FTL1 protein disrupts brain energy pathways, fuelling dementia-like symptoms—while NADH shows potential to restore memory and neural connections
Our brain functions through a network of interconnected cells that allow us to remember, learn, and adapt. But just like in humans, these processes gradually weaken with age—and scientists have observed the same in mice. University of California, San Francisco (UCSF) published a study in Nature Aging on August 19, 2025, that explains how a protein called ferritin light chain 1 (FTL1) regulates brain aging in mice and how NADH, a cellular energy molecule, has potential to mitigate memory loss associated with age-related diseases such as dementia.
What is FTL1?
FTL1, short for ferritin light chain 1, is a protein your body makes to manage iron in cells, including those in the brain. Iron is important because it helps brain cells create energy and communicate with each other. Too much iron, though, can cause trouble, like sparking harmful chemical reactions. FTL1 is part of a storage system called ferritin, which acts like a safe to keep extra iron locked away. The UCSF researchers used advanced techniques, like RNA sequencing and protein analysis, to find that FTL1 levels increase in the brains of older mice, specifically in the hippocampus—the part that handles memory.
How does FTL1 affect brain aging and memory loss in mice, and what’s NADH’s role?
The UCSF researchers found that in older mice (18–20 months), FTL1 levels in the hippocampus get too high. This traps too much iron, which causes inflammation and damage to the connections between brain cells. These connections are crucial for memory and learning, so when they weaken, the mice struggle with tasks like recognizing new objects or navigating a maze—signs of brain aging similar to dementia symptoms in humans. To test this, the researchers raised FTL1 in young mice (3 months old) and saw their brains act older: memory weakened, and brain cell connections broke down.
Here’s where it gets hopeful. When FTL1 was reduced in older mice using shRNA knockdown or CRISPR–Cas9 knockout, brain cell connections improved, synaptic proteins increased, and memory performance in NOR and Y maze tasks returned to youthful levels. A critical finding was FTL1’s impact on metabolism: RNA sequencing showed it disrupts energy pathways like ATP synthesis and oxidative phosphorylation, which are vital for brain function. The researchers tested NADH (nicotinamide adenine dinucleotide, reduced form), a coenzyme that supports ATP production in mitochondria. In primary neurons overexpressing FTL1, NADH treatment (200 µM daily for 5 days) restored neurite length and dendritic complexity. In young mice with high FTL1, NADH improved NOR and Y maze performance, linked to increased ATP production (via Seahorse assay). This suggests NADH may counteract FTL1-driven memory loss in mice by boosting energy pathways, offering insights into addressing cognitive decline in aging-related diseases.
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Can you get FTL1 from food?
No. FTL1 is not found in food; it’s made by your body’s cells based on genetic instructions. The UCSF study notes that dietary iron (from foods like meat, beans, or spinach) influences iron levels, which FTL1 regulates. A balanced diet supports healthy iron levels, but you cannot directly alter FTL1 through food, and the study does not explore dietary FTL1 modulation.
The UCSF study, conducted solely on mice, highlights FTL1 as a driver of brain aging and positions NADH as a potential memory-restoring supplement by addressing metabolic deficits. While not yet applicable to humans, these findings open doors to future treatments for cognitive decline. All credit goes to the University of California, San Francisco (UCSF) for this research.
