Initiated in the 1980s in collaboration with the National Institute on Aging, the study followed two groups over decades: one consuming a normal diet, and the other eating roughly 30% fewer calories.
Subjects lived out their full lifespans, with researchers analyzing their brain cells postmortem using advanced single nuclei RNA sequencing to assess gene expression and metabolic pathways.
The methodology involved detailed molecular profiling of individual brain cells, comparing those from calorie-restricted versus normal diet groups. This allowed researchers to pinpoint differences in genes related to myelin—the insulating sheath around nerve fibers crucial for fast, accurate neural communication.
They found that calorie-restricted brains exhibited enhanced expression of myelin-associated genes and increased activity in glycolytic and fatty acid biosynthesis pathways, essential for myelin production and maintenance.
These brain cells were metabolically healthier and more functional, suggesting long-term calorie restriction supports cellular resilience and slows neurodegenerative processes.
Co-author Dr. Tara L. Moore emphasized that these molecular alterations could underlie better cognition and learning observed in calorie-restricted subjects. The study sheds new light on how sustained dietary habits influence the brain’s aging trajectory on a cellular level.
This research adds important validation to calorie restriction as a potential intervention to maintain brain health and delay cognitive decline in humans, building on previous short-lived animal studies.
While implementing long-term calorie reduction poses challenges, these findings deepen understanding of modifiable lifestyle factors in brain aging. Ongoing exploration of CR’s effects could guide development of strategies to promote healthy cognitive aging and reduce neurodegenerative disease risk, improving quality of life across aging populations.
REFERENCE: Vitantonio, A.T., et al. (2025). Calorie Restriction Attenuates Transcriptional Aging Signatures in White Matter Oligodendrocytes and Immune Cells of the Monkey Brain. Aging Cell. DOI: 10.1111/acel.70298. https://onlinelibrary.wiley.com/doi/10.1111/acel.70298
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