brain aging

Brain Boosters: Researchers Identify Key Energy Molecule Decline in Aging,Find Potential Reversal with Supplement Combination

Irvine,CA – A new study from UC Irvine researchers reveals a critical energy deficit within brain cells as we age,specifically a decline in the molecule GTP (guanosine triphosphate),which impacts vital cellular processes like waste removal adn protein clearance. the research, published in GeroScience, identifies a potential pathway to restore youthful brain function through a combination of supplements – nicotinamide and EGCG – though a recent clinical trial showed oral nicotinamide alone is quickly broken down in the bloodstream.

This revelation offers a promising new angle in the fight against age-related cognitive decline and neurodegenerative diseases like AlzheimerS. While the search for effective interventions continues, understanding the basic energy limitations within brain cells is proving crucial.

The Energy Crisis Within Brain Cells

For years,scientists have understood that ATP (adenosine triphosphate) is a primary energy source for cellular functions. However, this new research highlights the equally vital role of GTP in powering essential processes like endocytosis (the process by which cells absorb substances) and autophagy (the cellular “self-cleaning” process that removes damaged components).

Researchers,led by gregory Brewer,used a novel fluorescent sensor to measure GTP levels in living neurons taken from aged Alzheimer’s model mice. They found a significant age-related reduction in free GTP, particularly within the mitochondria – the cell’s powerhouses. This decline was accompanied by a buildup of GTP-labeled vesicles, suggesting a disruption in cellular trafficking.

“age-related ATP depletion would impact cognition dependent on ionic homeostasis, but limits on proteostasis powered by GTP are less clear,” the study authors wrote. “Our results reveal age- and AD-related neuronal GTP energy deficits that impair autophagy and endocytosis.”

Restoring Youthful function: A Two-Pronged Approach

The team then investigated whether supplementation could restore GTP levels. They found that a combination of nicotinamide (an NAD precursor) and EGCG (a Nrf2 redox modulator, found in green tea) effectively boosted GTP levels back to those seen in younger neurons.

This restoration of GTP led to a revitalization of endocytosis and autophagy, ultimately improving neuronal viability, reducing protein damage, and even promoting the clearance of amyloid-beta (Aβ) aggregates – a hallmark of Alzheimer’s disease.

Interestingly, the researchers acknowledge that a recent clinical trial demonstrated oral nicotinamide isn’t effectively utilized due to inactivation in the bloodstream, suggesting alternative delivery methods or formulations may be necessary to maximize its benefits.

Looking Ahead: A Translational Path to Combatting Brain Aging

The study’s findings suggest a potential “translational path” – meaning a pathway from laboratory research to practical treatments – for addressing age-related cognitive decline. While further research is needed to determine the optimal dosage,delivery methods,and long-term effects of this supplement combination,the identification of GTP as a key player in brain aging represents a significant step forward.

The research was funded by the National Institutes of Health and the UC Irvine Foundation. Collaborators included Ricardo santana, a UC Irvine associate specialist in biomedical engineering, and Joshua McWhirt, a UC Irvine junior specialist now pursuing a Ph.D. at the Medical University of South Carolina.

Original research:

“Treatment of age-related decreases in GTP levels restores endocytosis and autophagy” by Gregory Brewer et al. GeroScience. https://dx.doi.org/10.1007/s11357-025-01786-4