Researchers at the National University of Singapore have identified a natural aging-related molecule that may help restore memory functions affected by Alzheimer’s disease. The compound, known as calcium alpha-ketoglutarate (CaAKG), improves communication between brain cells and enhances early memory abilities that typically decline first in Alzheimer’s patients. This breakthrough suggests a safer approach to protect brain health by utilizing a substance already present in the body.
The study, published on January 25, 2026, in the journal Aging Cell, was led by Professor Brian K. Kennedy, who heads the Department of Biochemistry and chairs the Healthy Longevity Translational Research Programme at NUS Medicine. The research aimed to explore whether CaAKG could improve synaptic plasticity, restore memory-related signaling, and protect neurons from the early degeneration commonly seen in Alzheimer’s disease.
Key Findings on CaAKG and Memory Restoration
The findings indicate that CaAKG enhances communication between brain cells in Alzheimer’s models, repairing weakened signaling pathways and restoring associative memory. This type of memory is one of the first cognitive functions to deteriorate in individuals with Alzheimer’s. The study’s implications suggest that boosting CaAKG levels, which naturally decline with age, could be an effective strategy for supporting brain health over time and potentially reducing the risk of neurodegenerative diseases.
“Our findings reveal the exciting potential of longevity compounds in addressing Alzheimer’s disease,” said Professor Kennedy. “Safe, natural compounds like CaAKG may one day complement existing approaches to protect the brain and slow memory loss.”
To understand how CaAKG produces these effects, the research team focused on long-term potentiation (LTP), a process essential for learning and long-term memory. In Alzheimer’s patients, LTP is severely disrupted. The study found that CaAKG restored LTP to normal levels, thereby enhancing the brain’s ability to form and retain memories.
Mechanisms Behind CaAKG’s Benefits
CaAKG also positively influenced autophagy, the brain’s internal cleanup system responsible for removing damaged proteins and maintaining neuronal health. The researchers revealed that CaAKG acts through a newly identified pathway, activating L-type calcium channels and calcium-permeable AMPA receptors while bypassing NMDA receptors, which are often impaired due to amyloid plaque buildup in Alzheimer’s.
Moreover, CaAKG restored synaptic tagging and capture, a critical mechanism that allows the brain to link experiences and form associative memories. This suggests that the compound may not only support basic memory functions but also enhance higher-level learning abilities that are often affected early in Alzheimer’s disease.
“Our goal was to determine whether a compound originally explored for extending healthy lifespan could be helpful for Alzheimer’s disease,” said Dr. Sheeja Navakkode, the study’s first author and a research scientist at the Healthy Longevity TRP. “Understanding the cellular mechanisms of how CaAKG improves synaptic plasticity sheds light on new ways to protect memory and slow brain aging.”
The research opens the door to innovative geroprotective strategies—treatments that target the biology of aging rather than simply addressing the symptoms of individual diseases. As the global population ages, such approaches may become increasingly vital for enhancing both the quality of life and cognitive longevity.
The study’s findings highlight the potential of leveraging the body’s natural compounds for therapeutic applications, paving the way for future research aimed at delaying cognitive decline and promoting healthy brain aging.
