Calorie Restriction Found to Have Impact on Brain Aging and Cellular Health

As the brain ages, metabolic dysfunction and oxidative damage impair cells in the central nervous system, reducing their ability to maintain the myelin sheath that protects nerve fibers, leading to age-related white matter degradation. Microglia, the brain’s immune cells, activate normally in response to injury or infection, but chronic activation during aging or Alzheimer’s disease causes damaging inflammation. The reasons for this chronic activation are not fully known. 

Researchers at Boston University investigated how long-term calorie restriction affects brain aging in an experimental model closely related to humans. Subjects consuming approximately 30% fewer calories for over 20 years were compared to a control group fed a normal diet. Their brains were analyzed after natural lifespans using single nuclei RNA sequencing to assess molecular changes in individual brain cells.

The calorie-restricted group exhibited metabolically healthier brain cells with increased expression of myelin-related genes and enhanced activity in glycolytic and fatty acid biosynthesis pathways, essential for myelin production and maintenance. These cellular changes suggest the brain remains more functional with calorie restriction. Ana Vitantonio, co-author of the study published in Aging Cell, highlighted that while calorie restriction is known to slow biological aging in shorter-lived models, this study offers rare long-term evidence for protective effects on brain aging in complex species.

According to the team, these findings support that long-term dietary interventions can shape the trajectory of brain aging on a cellular level. “This is important because these cellular alterations could have implications that are relevant to cognition and learning. In other words, dietary habits may influence brain health and eating fewer calories may slow some aspects of brain aging when implemented long term,” adds co-author Tara L. Moore.