Green tea compound and vitamin B3 derivative may restore the ability of aging brain cells to clear waste. Digest
As brain cells age, their cleanup systems lose efficiency, allowing damaged parts and sticky proteins to build up. To address this, a new study tried to restore guanosine triphosphate (GTP), which fuels cargo transport and recycling inside cells, to see if this could slow or even reverse the decline in aging neurons.
In neurons from healthy older mice and from a strain that develops Alzheimer-like changes, researchers tested whether a 24-hour treatment could restore GTP levels and improve waste processing. The treatment used two bioactive compounds: nicotinamide, a vitamin B3 derivative, and epigallocatechin gallate (EGCG), a green tea compound.
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The experiments revealed clear age-related declines as well as improvements after treatment:
- Aging neurons had lower GTP levels, including less free GTP near mitochondria. This decline appeared earlier in the Alzheimer-like strain.
- Treatment restored GTP to levels seen in young neurons.
- Signs of stalled transport inside cells decreased, suggesting cargo was moving to its destination more effectively.
- Amyloid-beta protein levels decreased inside neurons. Normally present in the brain, this protein can accumulate and form toxic clumps in Alzheimer's disease, damaging brain cells.
- When recycling pathways (autophagy) were blocked, GTP increased. When recycling was stimulated, GTP decreased. This confirmed that cleanup consumes significant GTP.
Two key cleanup routes in brain cells depend on GTP:
- Endocytosis brings materials into the cell for sorting or breakdown.
- Autophagy dismantles worn or damaged components and delivers them to the lysosome, a small acidic compartment that digests waste.
Both routes rely on moving materials inside the cell using tiny carriers that deliver their cargo to specific locations. This transport is directed by GTP-binding "switch" proteins, which turn on to move a carrier to the correct location and turn off once the delivery is complete. In older neurons, reduced GTP levels may slow these steps. Nicotinamide may help restore the cell's energy capacity, while EGCG may activate protective genes through the Nrf2 pathway, helping maintain the conditions needed for transport and recycling to function properly.
Conclusion:
The study shows that aging neurons had lower GTP and signs of slowed waste processing. Treatment with nicotinamide and EGCG restored GTP and improved cleanup markers. These results point to an energy bottleneck in cellular cleanup that can be relieved under controlled settings. However, the findings do not yet address brain function, long-term safety, or effectiveness in animals or humans. Learn more about how you can support your brain's ability to clear waste products in this episode.