As the brain grows older, the cells that support its function become increasingly prone to metabolic strain and oxidative stress. This gradual shift disrupts the delicate energy balance required for healthy neural activity. It undermines the maintenance of the myelin sheath, the insulating layer that enables efficient communication between nerve fibres. As myelin quality declines, white matter becomes more vulnerable to age-related deterioration. Alongside this, microglia—the immune cells that protect the brain—tend to move into a state of chronic activation during ageing. Although this response is meant to safeguard neural tissue, its persistence can create a damaging inflammatory environment, and researchers still do not fully understand why microglia behave in this way as the brain ages or in conditions such as Alzheimer’s disease.
Against this biological context, a new study from the Boston University Chobanian & Avedisian School of Medicine offers long-term evidence that reducing calorie intake may slow specific aspects of brain ageing. The research examined the effects of consuming roughly 30% fewer calories than usual over more than twenty years, using an experimental model that closely resembles human physiology. While calorie restriction has already been shown to influence longevity and biological ageing in short-lived species, opportunities to study its long-term impact in a complex organism are rare. This makes the new findings particularly significant, as they provide insight into how sustained dietary habits may shape the ageing brain at a cellular level.
According to the corresponding author, Ana Vitantonio, a PhD student in pharmacology, physiology and biophysics, the study adds valuable long-duration evidence to what is already known about the effects of calorie restriction. She notes that while the intervention has been studied extensively in simpler organisms, observing similar protective patterns in a more sophisticated model strengthens the case that diet can meaningfully influence brain ageing beyond basic metabolic markers.
The project was first launched in the 1980s in collaboration with the National Institute on Aging. Participants were divided into two groups: one consumed a standard, balanced diet, while the other adhered to a long-term calorie-restricted regimen. They lived out their natural lifespans, after which researchers examined their brains postmortem. This allowed the team to evaluate the cumulative cellular and molecular effects of decades of differing dietary intake.
Using single-nucleus RNA sequencing, the researchers compared gene expression profiles in individual brain cells from both groups. Cells from the calorie-restricted group appeared metabolically healthier, with increased expression of genes linked to myelin formation and more robust activity in metabolic pathways—particularly glycolytic and fatty-acid biosynthesis pathways—that are essential for myelin maintenance. These enhancements suggest that long-term calorie reduction may help preserve white matter integrity as the brain ages.
Co-author Tara L. Moore, professor of anatomy and neurobiology, emphasises that these cellular shifts may have meaningful consequences for cognition and learning. The study highlights the possibility that long-term dietary patterns, when carefully managed, could influence the biological trajectory of brain ageing and support healthier cognitive function later in life.
More information: Ana Vitantonio et al, Calorie Restriction Attenuates Transcriptional Aging Signatures in White Matter Oligodendrocytes and Immune Cells of the Monkey Brain, Aging Cell. DOI: 10.1111/acel.70298
Journal information: Aging Cell Provided by Boston University School of Medicine
