Calorie Restriction, Genes, and Brain Health: What Science from USC Suggests
Researchers from the University of Southern California have found a link between calorie restriction and improvements in brain health, along with a potential increase in life expectancy. The study, which appeared in Nature Communications, focuses on how changes in a specific gene can influence aging processes at the cellular level.
To uncover the mechanism behind the neuroprotective and longevity effects of restricted eating, the team studied fruit flies of diverse genetic backgrounds. From birth, the insects were divided into two feeding regimens. One group received a normal, adequate calorie intake. The other group was fed a diet that provided 10 percent fewer calories than the norm.
Through careful genetic analysis, the researchers identified five gene variants that significantly shape lifespan under nutritional restriction. Two of these genes have human counterparts. The scientists zeroed in on a gene named mustard in fruit flies, known in broader terms as Oxidation Resistance 1, or OXR1, which has parallels in humans and mice.
To reveal how OXR1 influences overall lifespan, the team conducted a series of in-depth laboratory experiments. They found that OXR1 modulates a cellular complex called retromer. This complex comprises a group of proteins essential for the correct processing of cellular proteins and lipids. When retromer function declines, the risk of age-related neurodegenerative diseases rises, with stronger links to conditions such as Alzheimer’s and Parkinson’s diseases observed in various models.
The researchers showed that calorie restriction leads to higher OXR1 expression in cells. As OXR1 levels rise, retromer performance also improves, supporting the protection of body cells, including neurons, from damage. This coordinated effect may contribute to longer healthy lifespans and sharper cognitive function in older adults.
Beyond these findings, the study aligns with a broader scientific interest in dietary strategies that could promote healthy aging. The team notes that fasting-like regimens, or alternative approaches, might offer practical paths to harness such genetic mechanisms without the extremes of constant calorie restriction. The ongoing work aims to translate insights from fruit fly models to human biology, exploring how variations in the OXR1 and retromer pathways could be leveraged for neuroprotection and aging interventions in people. Although more research is needed, the results add a meaningful piece to the puzzle of how diet, genes, and brain health intersect over the lifespan.
In summary, the work highlights a tangible link between calorie restriction and cellular systems that safeguard neurons. By enhancing the activity of OXR1 and the retromer complex, restricted diets may help preserve cognitive function and extend healthy life years. This line of inquiry opens doors to potential therapies and lifestyle recommendations that could support aging populations as science moves toward practical, human-focused applications. The researchers emphasize the importance of continued study to determine how these genetic pathways operate in humans and how they might be optimized in real-world settings.