Researchers at the National University of Singapore have made significant strides in understanding how a natural aging molecule may aid in restoring memory functions impaired by Alzheimer’s disease. The study, published on January 25, 2026, in the journal Aging Cell, reveals that calcium alpha-ketoglutarate (CaAKG) can enhance communication between brain cells, potentially reversing early memory loss associated with the disease.
The investigation was led by Professor Brian K Kennedy, who chairs the Healthy Longevity Translational Research Programme at the Yong Loo Lin School of Medicine. The research team focused on whether CaAKG could improve synaptic plasticity—essential for learning and memory—in models of Alzheimer’s disease. Their findings indicate that boosting this naturally occurring metabolite may offer a safer avenue for protecting cognitive health as it declines with age.
The significance of this discovery is underscored by Singapore’s high life expectancy, which often comes with an extended period of poor health. Many residents face debilitating conditions such as Alzheimer’s in their later years. As researchers explore the biological processes of aging, they aim to prevent age-related disorders, suggesting a shift in how these conditions are approached.
Memory Restoration Potential
Professor Kennedy commented on the implications of their findings, stating, “Our research reveals the exciting potential of longevity compounds in addressing Alzheimer’s disease.” He emphasized that natural compounds like CaAKG could complement existing treatments, potentially leading to broader accessibility and fewer risks for patients.
The study demonstrated that CaAKG effectively repaired disrupted signaling between neurons, thereby restoring associative memory, which is often one of the first cognitive functions affected in Alzheimer’s patients. With levels of AKG naturally declining as individuals age, replenishing this molecule could support brain health and mitigate the risk of neurodegenerative diseases.
Mechanisms of Action
To understand how CaAKG influences brain function, the research team examined long-term potentiation (LTP)—a critical process that strengthens neuron connections and is vital for memory formation. In the context of Alzheimer’s, LTP is severely compromised. The researchers found that CaAKG not only restored LTP to normal levels but also enhanced autophagy, the brain’s mechanism for clearing damaged proteins and maintaining neuronal health.
This molecule operates through a newly identified pathway that activates L-type calcium channels and calcium-permeable AMPA receptors, while avoiding the often impaired NMDA receptors associated with amyloid buildup. The research suggests that CaAKG not only supports basic memory functions but may also enhance higher-level learning abilities that tend to decline early in Alzheimer’s progression.
Dr. Sheeja Navakkode, the study’s first author, noted, “Our goal was to determine whether a compound originally explored for extending healthy lifespan could be helpful for Alzheimer’s disease.” The insights gained into the cellular mechanisms by which CaAKG enhances synaptic plasticity could lead to innovative strategies for protecting memory and slowing brain aging.
As the global population ages, the urgency to find effective treatments for Alzheimer’s and related conditions grows. This research represents a promising step forward in the quest to enhance cognitive longevity and improve the quality of life for millions affected by neurodegenerative diseases.
