Singapore – A new study from the National University of Singapore (NUS) Yong Loo Lin School of Medicine suggests a naturally occurring molecule, calcium alpha-ketoglutarate (CaAKG), may offer a novel approach to protecting brain health and slowing the progression of Alzheimer’s disease. The research, published in in the journal Aging Cell, indicates that CaAKG can improve communication between brain cells and restore key memory functions impaired by the disease.
Alzheimer’s disease, a progressive neurodegenerative condition, is characterized by a decline in cognitive function, particularly memory. As the global population ages, the incidence of Alzheimer’s is rising, creating an urgent need for effective preventative and therapeutic strategies. Researchers at NUS Medicine are focusing on the biological processes of aging itself, exploring whether modifying these processes can prevent or delay the onset of age-related conditions like Alzheimer’s.
CaAKG, a metabolite linked to healthy aging, was found to restore crucial brain functions affected by Alzheimer’s. The study demonstrated that CaAKG not only repairs weakened signals between neurons but also restores associative memory – a type of short-term memory that is often one of the first cognitive abilities to decline in individuals with Alzheimer’s disease. This finding is particularly significant, as restoring this early memory function could potentially slow the overall progression of the disease.
“Our findings reveal the exciting potential of longevity compounds in addressing Alzheimer’s disease,” said Professor Brian K Kennedy, Department of Biochemistry and Chair of the Healthy Longevity Translational Research Programme at NUS Medicine. “The research suggests that safe, natural compounds like CaAKG may one day complement existing approaches to protect the brain and slow memory loss.”
Alpha-ketoglutarate (AKG) is a naturally occurring metabolite essential for basic cellular functions. CaAKG is a supplemental form of this metabolite. Previous research has shown that AKG can extend lifespan in simpler organisms like roundworms and fruit flies. Studies in mice have indicated that CaAKG is associated with both lifespan extension and improvements in healthspan – the period of life spent in good health.
The NUS Medicine study builds on this existing research, specifically examining the effects of CaAKG in the context of Alzheimer’s-related pathology using pre-clinical models. Researchers found that CaAKG enhances synaptic plasticity, restores memory-related signaling, and protects neurons from early degenerative changes.
Assistant Professor Ch’ng Toh Hean from Nanyang Technological University’s Lee Kong Chian School of Medicine and School of Biological Sciences, who studies the biology of long-term memory formation, described the results as “very intriguing and promising.” He explained that the study demonstrated the ability to restore some synaptic deficits in brain cells obtained from mice with Alzheimer’s-like symptoms, using experiments on a cellular model commonly used to study the molecular mechanisms of memory.
However, Professor Ch’ng cautioned that further testing, particularly behavioral studies in animals and ultimately human clinical trials, is necessary to validate these findings. The current research was conducted in vitro – meaning in a laboratory setting outside of a living organism – and requires confirmation through more comprehensive studies.
Professor Kennedy echoed this sentiment, emphasizing the need for further research. “At this stage, it would be premature to suggest that seniors could be prescribed CaAKG supplements alongside brain exercises or other interventions to prevent Alzheimer’s disease or slow memory loss,” he stated. He and his team are actively pursuing additional research on both CaAKG and AKG to better understand their roles in the aging process.
It’s important to note that both AKG and CaAKG are currently available as commercial supplements. However, Professor Kennedy stressed that human studies regarding their anti-aging effects remain limited. While the initial findings are encouraging, more rigorous clinical trials are needed to determine the safety and efficacy of CaAKG as a potential therapeutic intervention for Alzheimer’s disease and age-related cognitive decline.
Singapore, known for its high life expectancy, faces the challenge of ensuring a healthy quality of life for its aging population. This study represents a significant step towards addressing that challenge, offering a potential new strategy to delay cognitive decline and support healthy brain aging. The ultimate aim of the NUS Medicine research is to test the efficacy of CaAKG in human patients, paving the way for a future where age-related cognitive decline can be effectively managed and potentially prevented.
